1
|
Barbaro MR, Bianco F, Cremon C, Marasco G, Stanghellini V, Barbara G. A Probiotic Mixture of Lactobacillus rhamnosus LR 32, Bifidobacterium lactis BL 04, and Bifidobacterium longum BB 536 Counteracts the Increase in Permeability Induced by the Mucosal Mediators of Irritable Bowel Syndrome by Acting on Zonula Occludens 1. Int J Mol Sci 2025; 26:2656. [PMID: 40141298 PMCID: PMC11942538 DOI: 10.3390/ijms26062656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/11/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
Abstract
Irritable Bowel Syndrome (IBS) is a disorder of gut- brain interaction characterized by recurrent abdominal pain associated with altered bowel habits. The therapeutic options for IBS patients include the use of probiotics. The aim of this study was to assess the effect of a multi-strain probiotic made up by Lactobacillus rhamnosus LR 32, Bifidobacterium lactis BL 04, and Bifidobacterium longum BB 536 (Serobioma, Bromatech s.r.l., Milano, Italy) on an in vitro model of the intestinal epithelial barrier in the presence of mucosal mediators that are released by IBS patients. IBS (n = 28; IBS with predominant diarrhea, IBS-D = 10; IBS with predominant constipation, IBS-C = 9; and IBS with mixed bowel habits, IBS-M = 9) patients, diagnosed according to the Rome IV criteria, and asymptomatic controls (ACs, n = 7) were enrolled. Mucosal mediators that were spontaneously released by colonic biopsies were collected (supernatants). Two doses of Serobioma were tested with/without IBS/AC mediators. RNA was extracted from Caco-2 cells to evaluate the tight junction (TJ) expression. Serobioma (106 CFU/mL) significantly reinforced the Caco-2 monolayer compared to growth medium alone (p < 0.05). IBS supernatants significantly increased Caco-2 paracellular permeability compared to the AC supernatants. The co-incubation of Caco-2 cells with IBS supernatants and Serobioma (106 CFU/mL) avoided the paracellular permeability alterations that were induced by IBS supernatants alone (p < 0.001), and, in particular, IBS-D and IBS-M ones. The co-incubation of Serobioma (106 CFU/mL) and IBS-D supernatants significantly increased ZO-1 expression compared to Caco-2 cells incubated with supernatants alone (p < 0.05), as confirmed via qPCR analyses. Serobioma (106 CFU/mL) counteracts the paracellular permeability changes that are induced by IBS supernatants, in particular IBS-D and IBS-M supernatants, likely modulating ZO-1 expression.
Collapse
Affiliation(s)
- Maria Raffaella Barbaro
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| | - Francesca Bianco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
| | - Cesare Cremon
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
| | - Giovanni Marasco
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| | - Vincenzo Stanghellini
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, I-40138 Bologna, Italy; (M.R.B.); (F.B.); (C.C.); (G.M.); (V.S.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, I-40138 Bologna, Italy
| |
Collapse
|
2
|
Farah A, Paul P, Khan AS, Sarkar A, Laws S, Chaari A. Targeting gut microbiota dysbiosis in inflammatory bowel disease: a systematic review of current evidence. Front Med (Lausanne) 2025; 12:1435030. [PMID: 40041456 PMCID: PMC11876558 DOI: 10.3389/fmed.2025.1435030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Accepted: 01/31/2025] [Indexed: 03/06/2025] Open
Abstract
Introduction The dysbiosis of the gut microbiota has been identified as a central factor in the pathogenesis of inflammatory bowel disease (IBD), a chronic condition characterized by frequent recurrence and various adverse effects of traditional therapies. While treatments targeting the gut microbiota show promise, their efficacy in IBD management still requires extensive evaluation. Our systematic review analyzes recent studies to elucidate the advancements and challenges in treating IBD using microbial-based therapies. Methods Through a comprehensive systematic review spanning key scientific databases-PubMed, Embase, Cochrane, Web of Science, Scopus, and Google Scholar-we scrutinized the impact of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation (FMT) on individuals with IBD. Our detailed analysis covered study and participant demographics, along with seven key outcome measures: disease activity index, inflammatory markers, serum cytokines, microbiome composition, adverse effects, and the rates of remission and relapse. Results From 6,080 initial search hits, we included 71 studies that assessed various interventions compared to placebo or standard medical therapy. Although there was notable variation in clinical results while assessing different outcomes, overall, probiotics, prebiotics, and synbiotics enhanced the success rates in inducing remission among IBD patients. Furthermore, we noted significant reductions in levels of pro-inflammatory markers and cytokines. Additionally, the requirement for steroids, hospitalization, and poor outcomes in endoscopic and histological scores were significantly reduced in individuals undergoing FMT. Conclusion Our investigation highlights the potential of targeting gut microbiota dysbiosis with microbial-based therapies in patients with IBD. We recommend conducting larger, placebo-controlled randomized trials with extended follow-up periods to thoroughly assess these treatments' clinical efficacy and safety before widespread recommendations for clinical application.
Collapse
Affiliation(s)
| | | | | | | | | | - Ali Chaari
- Weill Cornell Medicine–Qatar, Qatar Foundation, Education City, Doha, Qatar
| |
Collapse
|
3
|
Zhang T, Li X, Li J, Sun F, Duan L. Gut microbiome-targeted therapies as adjuvant treatments in inflammatory bowel diseases: a systematic review and network meta-analysis. J Gastroenterol Hepatol 2025; 40:78-88. [PMID: 39482823 DOI: 10.1111/jgh.16795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 09/10/2024] [Accepted: 10/15/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND AND AIM Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD). METHODS We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values. RESULTS Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD. CONCLUSIONS FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.
Collapse
Affiliation(s)
- Tao Zhang
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Xiaoang Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Jun Li
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| | - Feng Sun
- China Center for Evidence Based Medical and Clinical Research, Peking University, Beijing, China
- Institute of Public Health, Peking University, Beijing, China
| | - Liping Duan
- Department of Gastroenterology, Peking University Third Hospital, Beijing, China
| |
Collapse
|
4
|
Mousa WK, Al Ali A. The Gut Microbiome Advances Precision Medicine and Diagnostics for Inflammatory Bowel Diseases. Int J Mol Sci 2024; 25:11259. [PMID: 39457040 PMCID: PMC11508888 DOI: 10.3390/ijms252011259] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/12/2024] [Accepted: 10/13/2024] [Indexed: 10/28/2024] Open
Abstract
The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.
Collapse
Affiliation(s)
- Walaa K. Mousa
- College of Pharmacy, Al Ain University of Science and Technology, Abu Dhabi 64141, United Arab Emirates;
- College of Pharmacy, Mansoura University, Mansoura 35516, Egypt
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 112612, United Arab Emirates
| | - Aya Al Ali
- College of Pharmacy, Al Ain University of Science and Technology, Abu Dhabi 64141, United Arab Emirates;
- AAU Health and Biomedical Research Center, Al Ain University, Abu Dhabi 112612, United Arab Emirates
| |
Collapse
|
5
|
Ray A, Moore TF, Naik DSL, Borsch DM. Insights into the Two Most Common Cancers of Primitive Gut-Derived Structures and Their Microbial Connections. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1515. [PMID: 39336556 PMCID: PMC11434611 DOI: 10.3390/medicina60091515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 09/11/2024] [Accepted: 09/14/2024] [Indexed: 09/30/2024]
Abstract
The gastrointestinal and respiratory systems are closely linked in different ways, including from the embryological, anatomical, cellular, and physiological angles. The highest number (and various types) of microorganisms live in the large intestine/colon, and constitute the normal microbiota in healthy people. Adverse alterations of the microbiota or dysbiosis can lead to chronic inflammation. If this detrimental condition persists, a sequence of pathological events can occur, such as inflammatory bowel disease, dysplasia or premalignant changes, and finally, cancer. One of the most commonly identified bacteria in both inflammatory bowel disease and colon cancer is Escherichia coli. On the other hand, patients with inflammatory bowel disease are at risk of several other diseases-both intestinal (such as malnutrition and intestinal obstruction, besides cancer) and extraintestinal (such as arthritis, bronchiectasis, and cancer risk). Cancers of the lung and colon are the two most common malignancies occurring worldwide (except for female breast cancer). Like the bacterial role in colon cancer, many studies have shown a link between chronic Chlamydia pneumoniae infection and lung cancer. However, in colon cancer, genotoxic colibactin-producing E. coli belonging to the B2 phylogroup may promote tumorigenesis. Furthermore, E. coli is believed to play an important role in the dissemination of cancer cells from the primary colonic site. Currently, seven enteric pathogenic E. coli subtypes have been described. Conversely, three Chlamydiae can cause infections in humans (C. trachomatis may increase the risk of cervical and ovarian cancers). Nonetheless, striking genomic plasticity and genetic modifications allow E. coli to constantly adjust to the surrounding environment. Consequently, E. coli becomes resistant to antibiotics and difficult to manage. To solve this problem, scientists are thinking of utilizing suitable lytic bacteriophages (viruses that infect and kill bacteria). Several bacteriophages of E. coli and Chlamydia species are being evaluated for this purpose.
Collapse
Affiliation(s)
- Amitabha Ray
- School of Health Professions, D’Youville University, 320 Porter Ave, Buffalo, NY 14201, USA
| | - Thomas F. Moore
- College of Health Sciences, Glenville State University, Glenville, WV 26351, USA;
| | - Dayalu S. L. Naik
- ICMR National Institute of Traditional Medicine, Belagavi 590010, India;
| | - Daniel M. Borsch
- Lake Erie College of Osteopathic Medicine at Seton Hill, Greensburg, PA 15601, USA;
| |
Collapse
|
6
|
Estevinho MM, Yuan Y, Rodríguez‐Lago I, Sousa‐Pimenta M, Dias CC, Barreiro‐de Acosta M, Jairath V, Magro F. Efficacy and safety of probiotics in IBD: An overview of systematic reviews and updated meta-analysis of randomized controlled trials. United European Gastroenterol J 2024; 12:960-981. [PMID: 39106167 PMCID: PMC11497663 DOI: 10.1002/ueg2.12636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Accepted: 06/27/2024] [Indexed: 08/09/2024] Open
Abstract
BACKGROUND AND OBJECTIVE Probiotics show promise in inflammatory bowel disease (IBD), yet knowledge gaps persist. We performed an overview of systematic reviews and an updated metanalysis of randomized controlled trials (RCT) assessing the effect of probiotics on Crohn's disease (CD) and ulcerative colitis (UC). METHODS MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to September 2023. Primary outcomes were clinical remission and recurrence; secondary outcomes included endoscopic response and remission, and adverse events. We calculated odds ratios (OR) using a random-effects model in R. The quality of systematic reviews was assessed using the AMSTAR-2; the trials' risk of bias was evaluated using the Cochrane Collaboration tool. Evidence certainty was rated using the GRADE framework. RESULTS Out of 2613 results, 67 studies (22 systematic reviews and 45 RCTs) met the eligibility criteria. In the updated meta-analysis, the OR for clinical remission in UC and CD was 2.00 (95% CI 1.28-3.11) and 1.61 (95% CI 0.21-12.50), respectively. The subgroup analysis suggested that combining 5-ASA and probiotics may be beneficial for inducing remission in mild-to-moderate UC (OR 2.35, 95% CI 1.29-4.28). Probiotics decreased the odds of recurrence in relapsing pouchitis (OR 0.03, 95% CI 0.00-0.25) and trended toward reducing clinical recurrence in inactive UC (OR 0.65, 95% CI 0.42-1.01). No protective effect against recurrence was identified for CD. Multi-strain formulations appear superior in achieving remission and preventing recurrence in UC. The use of probiotics was not associated with better endoscopic outcomes. Adverse events were similar to control. However, the overall certainty of evidence was low. CONCLUSION Probiotics, particularly multi-strain formulations, appear efficacious for the induction of clinical remission and the prevention of relapse in UC patients as well as for relapsing pouchitis. Notwithstanding, no significant effect was identified for CD. The favorable safety profile of probiotics was also highlighted.
Collapse
Affiliation(s)
- Maria Manuela Estevinho
- Department of GastroenterologyUnidade Local de Saúde Gaia Espinho (ULSGE)Vila Nova de GaiaPortugal
- Department of BiomedicineUnit of Pharmacology and TherapeuticsFaculty of MedicineUniversity of PortoPortoPortugal
| | - Yuhong Yuan
- Department of MedicineLondon Health Science CenterLondonOntarioCanada
- Division of GastroenterologyDepartment of MedicineWestern UniversityLondonOntarioCanada
| | - Iago Rodríguez‐Lago
- Department of GastroenterologyHospital Universitario de GaldakaoBiocruces Bizkaia Health Research InstituteDeusto UniversityGaldakaoSpain
| | - Mário Sousa‐Pimenta
- Department of BiomedicineUnit of Pharmacology and TherapeuticsFaculty of MedicineUniversity of PortoPortoPortugal
- i3S ‐ Instituto de Investigação e Inovação em SaúdeUniversidade do PortoPortoPortugal
| | - Cláudia Camila Dias
- Knowledge Management UnitFaculty of MedicineUniversity of PortoPortoPortugal
- CINTESIS@RISEDepartment of Community MedicineInformation and Health Decision Sciences (MEDCIDS)Faculty of Medicine of the University of Porto (FMUP)PortoPortugal
| | | | - Vipul Jairath
- Division of GastroenterologyDepartment of MedicineWestern UniversityLondonOntarioCanada
- Alimentiv, Inc.LondonOntarioCanada
- Department of Epidemiology and BiostatisticsWestern UniversityLondonOntarioCanada
| | - Fernando Magro
- CINTESIS@RISEDepartment of Community MedicineInformation and Health Decision Sciences (MEDCIDS)Faculty of Medicine of the University of Porto (FMUP)PortoPortugal
- Department of GastroenterologyUnidade Local de Saúde São João (ULSSJ)PortoPortugal
| |
Collapse
|
7
|
Wang X, Zhou C, Zhang S, Ma Y, Xiao W, Guo Y. Additive efficacy and safety of probiotics in the treatment of ulcerative colitis: a systematic review and meta-analysis. Eur J Nutr 2024; 63:1395-1411. [PMID: 38446227 DOI: 10.1007/s00394-023-03307-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/08/2023] [Indexed: 03/07/2024]
Abstract
BACKGROUND We aim to report the latest pooled analyses to evaluate the additive efficacy and safety of probiotics in the treatment of ulcerative colitis (UC). METHODS We systematically searched the relevant literature investigating the efficacy and/or safety of probiotics in patients with UC from PubMed, Embase and Web of Science up to January 2023. Two researchers independently screened the literature, extracted data, and evaluated the quality of the included studies according to the inclusion and exclusion criteria. Any discrepancies throughout these processes were solved by consensus. All statistical analyses were performed by Review Manager version 5.4 and Stata version 15.0. RESULTS A total of 13 articles were included in the pooled analyses, and the studies were all randomized controlled trials with a total of 930 patients. There were no significant differences between the probiotics and placebo groups concerning demographic and baseline characteristics. For patients with active UC, the probiotic group boosted the remission rate by 87% compared to the placebo group, but failed to reach a statistical difference (OR: 1.87; 95% CI 0.98, 3.57; P = 0.06, I2 = 67%); furthermore, there were no statistical differences in maintenance of clinical remission, clinical response, change in UCDAI scores, or mucosal healing outcomes in the probiotic group compared to the placebo group. For patients in clinical remission, the clinical relapse rates were significantly lower in the probiotic group than in the placebo group (OR: 0.34; 95% CI 0.14, 0.79; P = 0.01). Moreover, this study did not observe a significant difference between the two groups for general adverse events rate (OR: 1.98; 95% CI 0.69, 5.68; P = 0.20). CONCLUSION Probiotic-assisted therapy may be effective in inhibiting UC recurrence in patients in clinical remission without increasing the risk of treatment-related adverse events; furthermore, probiotics may increase the rate of clinical remission in patients with active UC. However, caution is needed when interpreting the clinical efficacy of probiotics in improving the clinical outcome of patients with active UC.
Collapse
Affiliation(s)
- Xinyue Wang
- Beijing University of Chinese Medicine, Beijing, China
| | - Chunyu Zhou
- Medical Management Office of Beijing University of Chinese Medicine, Beijing, China.
| | - Shaohui Zhang
- Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing, China
| | - Yixiang Ma
- Beijing University of Chinese Medicine, Beijing, China
| | - Wenqin Xiao
- Beijing University of Chinese Medicine, Beijing, China
| | - Yanmei Guo
- Beijing University of Chinese Medicine, Beijing, China
| |
Collapse
|
8
|
Bosselaar S, Dhelin L, Dautel E, Titecat M, Duthoy S, Stelmaszczyk M, Delory N, De Sousa Violante M, Machuron F, Ait-Abderrahim H, Desreumaux P, Foligné B, Monnet C. Taxonomic and phenotypic analysis of bifidobacteria isolated from IBD patients as potential probiotic strains. BMC Microbiol 2024; 24:233. [PMID: 38951788 PMCID: PMC11218132 DOI: 10.1186/s12866-024-03368-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 06/12/2024] [Indexed: 07/03/2024] Open
Abstract
BACKGROUND Inflammatory Bowel Diseases (IBD) are a major public health issue with unclear aetiology. Changes in the composition and functionality of the intestinal microbiota are associated with these pathologies, including the depletion of strict anaerobes such as Feacalibacterium prausnitzii. Less evidence is observed for depletion in other anaerobes, among which bifidobacteria. This study characterized the taxonomic and functional diversity of bifidobacteria isolated from the human intestinal microbiota in active and non-active IBD patients by a culturomics approach and evaluated if these bifidobacteria might be used as probiotics for gut health. RESULTS A total of 341 bifidobacteria were isolated from the intestinal microbiota of IBD patients (52 Crohn's disease and 26 ulcerative colitis patients), with a high proportion of Bifidobacterium dentium strains (28% of isolated bifidobacteria). In ulcerative colitis, the major species identified was B. dentium (39% of isolated bifidobacteria), in active and non-active ulcerative colitis. In Crohn's disease, B. adolescentis was the major species isolated from non-active patients (40%), while similar amounts of B. dentium and B. adolescentis were found in active Crohn's disease patients. The relative abundance of B. dentium was increased with age, both in Crohn's disease and ulcerative colitis and active and non-active IBD patients. Antibacterial capacities of bifidobacteria isolated from non-active ulcerative colitis against Escherichia coli LF82 and Salmonella enterica ATCC 14028 were observed more often compared to strains isolated from active ulcerative colitis. Finally, B. longum were retained as strains with the highest probiotic potential as they were the major strains presenting exopolysaccharide synthesis, antibacterial activity, and anti-inflammatory capacities. Antimicrobial activity and EPS synthesis were further correlated to the presence of antimicrobial and EPS gene clusters by in silico analysis. CONCLUSIONS Different bifidobacterial taxonomic profiles were identified in the microbiota of IBD patients. The most abundant species were B. dentium, mainly associated to the microbiota of ulcerative colitis patients and B. adolescentis, in the intestinal microbiota of Crohn's disease patients. Additionally, the relative abundance of B. dentium significantly increased with age. Furthermore, this study evidenced that bifidobacteria with probiotic potential (antipathogenic activity, exopolysaccharide production and anti-inflammatory activity), especially B. longum strains, can be isolated from the intestinal microbiota of both active and non-active Crohn's disease and ulcerative colitis patients.
Collapse
Affiliation(s)
- Sabine Bosselaar
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France.
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France.
| | - Lucile Dhelin
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Ellena Dautel
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Marie Titecat
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France
| | - Stéphanie Duthoy
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Marie Stelmaszczyk
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Nathan Delory
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Madeleine De Sousa Violante
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - François Machuron
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Hassina Ait-Abderrahim
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| | - Pierre Desreumaux
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France
- Department of Hepato-Gastroenterology, Lille University Hospital, 59037, Lille, France
| | - Benoit Foligné
- Univ. Lille, Inserm, CHU Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, 59000, Lille, France
| | - Céline Monnet
- Lesaffre International - Lesaffre Institute of Science and Technology, 101 Rue de Menin, 59706, Marcq-en-Barœul, France
| |
Collapse
|
9
|
Kasapoglu M, Yadavalli R, Nawaz S, Althwanay A, AlEdani EM, Kaur H, Butt S. The Impact of Microbiome Interventions on the Progression and Severity of Inflammatory Bowel Disease: A Systematic Review. Cureus 2024; 16:e60786. [PMID: 38779440 PMCID: PMC11110475 DOI: 10.7759/cureus.60786] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Accepted: 05/21/2024] [Indexed: 05/25/2024] Open
Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation. The dysbiotic gut microbiome likely contributes to IBD pathogenesis. Microbiome-directed therapies such as fecal microbiota transplantation (FMT), probiotics, and synbiotics may help induce and maintain remission. This systematic review aimed to determine the efficacy of microbiome interventions compared to standard therapy or placebo for IBD treatment. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for randomized controlled trials on microbiome interventions in IBD from inception to October 2023. The risk of bias was assessed using Cochrane tools. Outcomes included disease activity, endoscopy, histology, quality of life, and adverse events. A total of 18 randomized controlled trials were included. Three trials found intensive (i.e., high frequency of administration and/or large volumes of fecal material) multi-donor FMT superior to autologous FMT or glucocorticoids for UC remission induction. Seven placebo-controlled trials demonstrated higher remission rates with FMT, especially intensive protocols, versus control for mild-to-moderate UC. However, a single FMT did not prevent relapses. Seven probiotic trials showed the potential to improve UC activity and maintain remission. One synbiotic trial reported reduced inflammation and symptoms versus placebo. Serious adverse events were rare. Small sample sizes and protocol heterogeneity limited the conclusions. Current evidence indicates the potential benefits of microbiome interventions, particularly intensive multi-donor FMT, for inducing and maintaining remission in UC. Probiotics may also improve outcomes. Adequately powered trials using standardized protocols are still needed to firmly establish efficacy and safety. Microbiome-directed therapies represent a promising approach for improving IBD outcomes.
Collapse
Affiliation(s)
- Malik Kasapoglu
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Rajesh Yadavalli
- Internal Medicine, Rajiv Gandhi Institute of Medical Sciences, Adilabad, IND
| | - Sarosh Nawaz
- Psychiatry, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Abdulaziz Althwanay
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Medicine, Imam Abdulrahman Bin Faisal University, Dammam, SAU
| | - Esraa M AlEdani
- Dermatology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Harleen Kaur
- Medicine and Surgery, Maharishi Markandeshwar Institute of Medical Sciences and Research, Mullana, IND
| | - Samia Butt
- Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| |
Collapse
|
10
|
Wang X, Dong F, Liu G, Ye L, Xiao F, Li X, Zhang T, Wang Y. Probiotic properties and the ameliorative effect on DSS-induced colitis of human milk-derived Lactobacillus gasseri SHMB 0001. J Food Sci 2024; 89:3078-3093. [PMID: 38605580 DOI: 10.1111/1750-3841.17057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 03/09/2024] [Accepted: 03/15/2024] [Indexed: 04/13/2024]
Abstract
Human milk contains a variety of microorganisms that exert benefit for human health. In the current study, we isolated a novel Lactobacillus gasseri strain named Lactobacillus gasseri (L. gasseri) SHMB 0001 from human milk and aimed to evaluate the probiotic characteristics and protective effects on murine colitis of the strain. The results showed that L. gasseri SHMB 0001 possessed promising potential probiotic characteristics, including good tolerance against artificial gastric and intestinal fluids, adhesion to Caco-2 cells, susceptibility to antibiotic, no hemolytic activity, and without signs of toxicity or infection in mice. Administration of L. gasseri SHMB 0001 (1 × 108 CFU per gram of mouse weight per day) reduced weight loss, the disease activity index, and colon shortening in mice during murine colitis conditions. Histopathological analysis revealed that L. gasseri SHMB 0001 treatment attenuated epithelial damage and inflammatory infiltration in the colon. L. gasseri SHMB 0001 treatment increased the expression of colonic occludin and claudin-1 while decreasing the expression of pro-inflammatory cytokine genes. L. gasseri SHMB 0001 modified the composition and structure of the gut microbiota community and partially recovered the Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways altered by dextran sulfate sodium (DSS). Overall, our results indicated that the human breast milk-derived L. gasseri SHMB 0001 exhibited promising probiotic properties and ameliorative effect on DSS-induced colitis in mice. L. gasseri SHMB 0001 may be applied as a promising probiotic against intestinal inflammation in the future. PRACTICAL APPLICATION: L. gasseri SHMB 0001 isolated from human breast milk showed good tolerance to gastrointestinal environment, safety, and protective effect against DSS-induced mice colitis via enforcing gut barrier, downregulating pro-inflammatory cytokines, and modulating gut microbiota. L. gasseri SHMB 0001 may be a promising probiotic candidate for the treatment of intestinal inflammation.
Collapse
Affiliation(s)
- Xufei Wang
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fang Dong
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gaojie Liu
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lin Ye
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fangfei Xiao
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaolu Li
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ting Zhang
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Donor Human Milk Bank, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yizhong Wang
- Department of Gastroenterology, Hepatology, and Nutrition, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Shanghai Donor Human Milk Bank, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| |
Collapse
|
11
|
Kennedy JM, De Silva A, Walton GE, Gibson GR. A review on the use of prebiotics in ulcerative colitis. Trends Microbiol 2024; 32:507-515. [PMID: 38065786 DOI: 10.1016/j.tim.2023.11.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 11/09/2023] [Accepted: 11/14/2023] [Indexed: 05/12/2024]
Abstract
The gut microbiome in the inflammatory bowel disease, ulcerative colitis (UC), is different to that of healthy controls. Patients with UC have relative reductions in abundance of Firmicutes and Bifidobacterium in the colon, and an increase in sulfate-reducing bacteria. Prebiotics are dietary substrates which are selectively metabolised by the human colonic microbiota to confer health benefits to the host. This review explores our current understanding of the potential benefits of prebiotics on various clinical, biochemical, and microbiological endpoints in UC, including new perspectives gained from recent studies in the field. This review looks to the future and highlights the need for appropriately designed trials to explore this potentially exciting new avenue for the treatment of UC.
Collapse
Affiliation(s)
- James M Kennedy
- Department of Food and Nutritional Sciences, The University of Reading, Reading, RG6 6AP, UK; Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading, RG1 5AN, UK.
| | - Aminda De Silva
- Department of Gastroenterology, Royal Berkshire NHS Foundation Trust, Reading, RG1 5AN, UK
| | - Gemma E Walton
- Department of Food and Nutritional Sciences, The University of Reading, Reading, RG6 6AP, UK
| | - Glenn R Gibson
- Department of Food and Nutritional Sciences, The University of Reading, Reading, RG6 6AP, UK
| |
Collapse
|
12
|
Gaur P, Rajendran Y, Srivastava B, Markandey M, Fishbain-Yoskovitz V, Mohapatra G, Suhail A, Chaudhary S, Tyagi S, Yadav SC, Pandey AK, Merbl Y, Bajaj A, Ahuja V, Srikanth C. Rab7-dependent regulation of goblet cell protein CLCA1 modulates gastrointestinal homeostasis. eLife 2024; 12:RP89776. [PMID: 38593125 PMCID: PMC11003743 DOI: 10.7554/elife.89776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024] Open
Abstract
Inflammation in ulcerative colitis is typically restricted to the mucosal layer of distal gut. Disrupted mucus barrier, coupled with microbial dysbiosis, has been reported to occur prior to the onset of inflammation. Here, we show the involvement of vesicular trafficking protein Rab7 in regulating the colonic mucus system. We identified a lowered Rab7 expression in goblet cells of colon during human and murine colitis. In vivo Rab7 knocked down mice (Rab7KD) displayed a compromised mucus layer, increased microbial permeability, and depleted gut microbiota with enhanced susceptibility to dextran sodium-sulfate induced colitis. These abnormalities emerged owing to altered mucus composition, as revealed by mucus proteomics, with increased expression of mucin protease chloride channel accessory 1 (CLCA1). Mechanistically, Rab7 maintained optimal CLCA1 levels by controlling its lysosomal degradation, a process that was dysregulated during colitis. Overall, our work establishes a role for Rab7-dependent control of CLCA1 secretion required for maintaining mucosal homeostasis.
Collapse
Affiliation(s)
- Preksha Gaur
- Laboratory of Gut Inflammation and Infection Biology, Regional Centre for BiotechnologyFaridabadIndia
| | - Yesheswini Rajendran
- Laboratory of Gut Inflammation and Infection Biology, Regional Centre for BiotechnologyFaridabadIndia
| | | | - Manasvini Markandey
- Department of Gastroenterology, All India Institute of Medical SciencesDelhiIndia
| | | | | | - Aamir Suhail
- Gene Lay Institute of Immunology and Inflammation, Brigham and Women’s Hospital, Massachusetts General Hospital and Harvard Medical SchoolBostonUnited States
| | - Shikha Chaudhary
- Department of Anatomy, All India Institute of Medical SciencesNew DelhiIndia
| | - Shaifali Tyagi
- Vaccine and Infectious Disease Research Center, Translational Health Science and Technology InstituteFaridabadIndia
| | | | - Amit Kumar Pandey
- Vaccine and Infectious Disease Research Center, Translational Health Science and Technology InstituteFaridabadIndia
| | - Yifat Merbl
- Department of Immunology, Weizmann Institute of ScienceRehovotIsrael
| | - Avinash Bajaj
- Laboratory of Gut Inflammation and Infection Biology, Regional Centre for BiotechnologyFaridabadIndia
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical SciencesDelhiIndia
| | - Chittur Srikanth
- Laboratory of Gut Inflammation and Infection Biology, Regional Centre for BiotechnologyFaridabadIndia
| |
Collapse
|
13
|
Ma Y, Yang D, Huang J, Liu K, Liu H, Wu H, Bao C. Probiotics for inflammatory bowel disease: Is there sufficient evidence? Open Life Sci 2024; 19:20220821. [PMID: 38585636 PMCID: PMC10998680 DOI: 10.1515/biol-2022-0821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 11/26/2023] [Accepted: 12/11/2023] [Indexed: 04/09/2024] Open
Abstract
Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.
Collapse
Affiliation(s)
- Yueying Ma
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Shanghai University of Traditional Chinese Medicine, Shanghai201203, China
| | - Dandan Yang
- Hong Kong Baptist University, Hong Kong999077, China
| | - Jin Huang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Shanghai University of Traditional Chinese Medicine, Shanghai201203, China
| | - Kunli Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Shanghai University of Traditional Chinese Medicine, Shanghai201203, China
| | - Huirong Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai200030, China
| | - Huangan Wu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai200030, China
| | - Chunhui Bao
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai200030, China
| |
Collapse
|
14
|
Wang S, Zhou S, Han Z, Yu B, Xu Y, Lin Y, Chen Y, Jin Z, Li Y, Cao Q, Xu Y, Zhang Q, Wang YC. From gut to brain: understanding the role of microbiota in inflammatory bowel disease. Front Immunol 2024; 15:1384270. [PMID: 38576620 PMCID: PMC10991805 DOI: 10.3389/fimmu.2024.1384270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 03/12/2024] [Indexed: 04/06/2024] Open
Abstract
With the proposal of the "biological-psychological-social" model, clinical decision-makers and researchers have paid more attention to the bidirectional interactive effects between psychological factors and diseases. The brain-gut-microbiota axis, as an important pathway for communication between the brain and the gut, plays an important role in the occurrence and development of inflammatory bowel disease. This article reviews the mechanism by which psychological disorders mediate inflammatory bowel disease by affecting the brain-gut-microbiota axis. Research progress on inflammatory bowel disease causing "comorbidities of mind and body" through the microbiota-gut-brain axis is also described. In addition, to meet the needs of individualized treatment, this article describes some nontraditional and easily overlooked treatment strategies that have led to new ideas for "psychosomatic treatment".
Collapse
Affiliation(s)
- Siyu Wang
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Shuwei Zhou
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Zhongyu Han
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| | - Bin Yu
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yin Xu
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yumeng Lin
- Eye School of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yutong Chen
- The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zi Jin
- Department of Anesthesiology and Pain Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China
| | - Yalong Li
- Anorectal Department, The Third Affiliated Hospital of Yunnan University of Chinese Medicine, Kunming, China
| | - Qinhan Cao
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine (TCM), Chengdu, China
| | - Yunying Xu
- Clinical Medical School, Affiliated Hospital of Chengdu University, Chengdu, China
| | - Qiang Zhang
- Department of Gastroenterology, The First Hospital of Hunan University of Chinese Medicine, Changsha, China
| | - Yuan-Cheng Wang
- Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
- Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
| |
Collapse
|
15
|
Zeng L, Yang K, He Q, Zhu X, Long Z, Wu Y, Chen J, Li Y, Zeng J, Cui G, Xiang W, Hao W, Sun L. Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials. BMC Med 2024; 22:110. [PMID: 38475833 PMCID: PMC10935932 DOI: 10.1186/s12916-024-03303-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 02/13/2024] [Indexed: 03/14/2024] Open
Abstract
BACKGROUND Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).
Collapse
Affiliation(s)
- Liuting Zeng
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
| | - Kailin Yang
- Hunan University of Chinese Medicine, Changsha, China
| | - Qi He
- People's Hospital of Ningxiang City, Ningxiang, China
| | | | - Zhiyong Long
- Department of Rehabilitation Medicine, Guangzhou Panyu Central Hospital, Guangzhou, China
| | - Yang Wu
- Department of Rheumatology, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | | | - Yuwei Li
- Hunan University of Science and Technology, Xiangtan, China
| | - Jinsong Zeng
- Department of Rheumatology, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ge Cui
- Department of Epidemiology and Statistics, School of Public Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Wang Xiang
- Department of Rheumatology, The First People's Hospital Changde City, Changde, China
| | - Wensa Hao
- Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Lingyun Sun
- Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
| |
Collapse
|
16
|
Rau S, Gregg A, Yaceczko S, Limketkai B. Prebiotics and Probiotics for Gastrointestinal Disorders. Nutrients 2024; 16:778. [PMID: 38542689 PMCID: PMC10975713 DOI: 10.3390/nu16060778] [Citation(s) in RCA: 33] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 03/05/2024] [Accepted: 03/06/2024] [Indexed: 01/03/2025] Open
Abstract
The complex role of the gut microbiome in the pathogenesis of gastrointestinal (GI) disorders is an emerging area of research, and there is considerable interest in understanding how diet can alter the composition and function of the microbiome. Prebiotics and probiotics have been shown to beneficially modulate the gut microbiome, which underlies their potential for benefit in GI conditions. Formulating specific recommendations for the public regarding these dietary supplements has been difficult due to the significant heterogeneity between strains, doses, and duration of treatment investigated across studies, as well as safety concerns with administering live organisms. This review aims to summarize the existing evidence for the use of prebiotics and probiotics in various GI disorders, paying special attention to strain-specific effects that emerged and any adverse effects noted.
Collapse
Affiliation(s)
| | | | | | - Berkeley Limketkai
- Vatche & Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA 90095, USA; (S.R.); (A.G.); (S.Y.)
| |
Collapse
|
17
|
Jakubczyk D, Leszczyńska K, Pacyga-Prus K, Kozakiewicz D, Kazana-Płuszka W, Gełej D, Migdał P, Kruszakin R, Zabłocka A, Górska S. What happens to Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum in an experimental environment with eukaryotic cells? BMC Microbiol 2024; 24:60. [PMID: 38373929 PMCID: PMC10875879 DOI: 10.1186/s12866-023-03179-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Accepted: 12/29/2023] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND The impact of probiotic strains on host health is widely known. The available studies on the interaction between bacteria and the host are focused on the changes induced by bacteria in the host mainly. The studies determining the changes that occurred in the bacteria cells are in the minority. Within this paper, we determined what happens to the selected Bifidobacterium adolescentis and Bifidobacterium longum ssp. longum in an experimental environment with the intestinal epithelial layer. For this purpose, we tested the bacteria cells' viability, redox activity, membrane potential and enzymatic activity in different environments, including CaCo-2/HT-29 co-culture, cell culture medium, presence of inflammatory inductor (TNF-α) and oxygen. RESULTS We indicated that the external milieu impacts the viability and vitality of bacteria. Bifidobacterium adolescentis decrease the size of the live population in the cell culture medium with and without TNF-α (p < 0.001 and p < 0.01 respectively). In contrast, Bifidobacterium longum ssp. longum significantly increased survivability in contact with the eukaryotic cells and cell culture medium (p < 0.001). Bifidobacterium adolescentis showed significant changes in membrane potential, which was decreased in the presence of eukaryotic cells (p < 0.01), eukaryotic cells in an inflammatory state (p < 0.01), cell culture medium (p < 0.01) and cell culture medium with TNF-α (p < 0.05). In contrast, Bifidobacterium longum ssp. longum did not modulate membrane potential. Instead, bacteria significantly decreased the redox activity in response to milieus such as eukaryotic cells presence, inflamed eukaryotic cells as well as the culture medium (p < 0.001). The redox activity was significantly different in the cells culture medium vs the presence of eukaryotic cells (p < 0.001). The ability to β-galactosidase production was different for selected strains: Bifidobacterium longum ssp. longum indicated 91.5% of positive cells, whereas Bifidobacterium adolescentis 4.34% only. Both strains significantly reduced the enzyme production in contact with the eukaryotic milieu but not in the cell culture media. CONCLUSION The environmental-induced changes may shape the probiotic properties of bacterial strains. It seems that the knowledge of the sensitivity of bacteria to the external environment may help to select the most promising probiotic strains, reduce research costs, and contribute to greater reproducibility of the obtained probiotic effects.
Collapse
Affiliation(s)
- Dominika Jakubczyk
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
| | - Katarzyna Leszczyńska
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Katarzyna Pacyga-Prus
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Dominika Kozakiewicz
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Wioletta Kazana-Płuszka
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Dominika Gełej
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Paweł Migdał
- Inter-Departmental Laboratory of Instrumental Analysis and Preparation, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Roksana Kruszakin
- Inter-Departmental Laboratory of Instrumental Analysis and Preparation, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Agnieszka Zabłocka
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| | - Sabina Górska
- Laboratory of Microbiome Immunobiology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland
| |
Collapse
|
18
|
Yinhe S, Lixiang L, Yan L, Xiang G, Yanqing L, Xiuli Z. Bacteroides thetaiotaomicron and its inactivated bacteria ameliorate colitis by inhibiting macrophage activation. Clin Res Hepatol Gastroenterol 2024; 48:102276. [PMID: 38158154 DOI: 10.1016/j.clinre.2023.102276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/16/2023] [Accepted: 12/27/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND Studies have demonstrated that Bacteroides thetaiotaomicron (BT) has protective effect against colon inflammation in murine models. Macrophages play an important role in gut immunity. However, the specific mechanisms of BT on macrophage are still unelucidated. Thus, our study investigates the anti-inflammatory effect of BT and its heat-treated inactivated bacteria on experimental colitis and macrophages. METHODS A dextran sulfate sodium (DSS)-induced acute colitis model with male C57BL/6 mice, BT (ATCC29148) strain, THP1 cell lines were used in this study. Live and heat-treated inactivated BT (IBT) solution (1 × 10^9cfu/ml) were intragastrically gavaged daily for 14 days. Colonic inflammation was determined by the disease activity index (DAI) score, colon length, histological score, and inflammatory factors. THP1 cells were induced towards M1, then treated with different concentrations of inactivated BT solution and p38 inhibitor. Western blotting, immunohistochemistry, immunofluorescence and qRT-PCR were performed to assess the levels of inflammatory cytokines and molecules of MAPK pathway including IL-6, TNF-α, IL-1β, IL-22, p38 and phosphor-p38 expressions. Moreover, 16S rRNA sequencing of colitis murine fecal samples was applied to investigate the influence of supplementation of BT to the gut microbiota homeostasis. RESULTS Both live and heat-treated inactivated BT decreased the DAI and histological scores as well as levels of inflammatory factors, particularly IL-6 while increasing IL-22 of DSS-induced colitis murine models. The cell experiments showed that inactivated BT downregulates IL-6 expression in THP1 via inhibiting p38 phosphorylation and affecting M1 polarization. Moreover, the 16S rRNA sequencing results showed that BT and IBT gavage could increase beta-diversity of gut flora in DSS-induced colitis mice. Furthermore, the significance test for differences between the groups showed that BT could increase Faecalebaculum, Lactobacillus and Bacteroides, while decreasing Akkermansia. CONCLUSION In summary, our findings imply that BT and its heat-treated inactivated bacteria exert a protective effect by suppressing macrophage-induced IL-6 through the inhibition of p38 MAPK pathway and ameliorating intestinal gut dysbiosis in experimental colitis.
Collapse
Affiliation(s)
- Sikong Yinhe
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Department of Gastroenterology, Qilu Hospital of Shandong University Qingdao, Qingdao, Shandong, PR China
| | - Li Lixiang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Shandong Provincial Clinical Research Center for digestive disease, Shandong, PR China
| | - Li Yan
- Department of Gastroenterology, Qilu Hospital of Shandong University Qingdao, Qingdao, Shandong, PR China
| | - Gu Xiang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
| | - Li Yanqing
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Department of Gastroenterology, Qilu Hospital of Shandong University Qingdao, Qingdao, Shandong, PR China; Shandong Provincial Clinical Research Center for digestive disease, Shandong, PR China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Robot engineering laboratory for precise diagnosis and therapy of GI tumor, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
| | - Zuo Xiuli
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Department of Gastroenterology, Qilu Hospital of Shandong University Qingdao, Qingdao, Shandong, PR China; Shandong Provincial Clinical Research Center for digestive disease, Shandong, PR China; Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China; Robot engineering laboratory for precise diagnosis and therapy of GI tumor, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
| |
Collapse
|
19
|
Go K, Horiba K, Yamamoto H, Morimoto Y, Fukasawa Y, Ohashi N, Yasuda K, Ishikawa Y, Kuraishi K, Suzuki K, Ito Y, Takahashi Y, Kato T. Dysbiosis of gut microbiota in patients with protein-losing enteropathy after the Fontan procedure. Int J Cardiol 2024; 396:131554. [PMID: 37875211 DOI: 10.1016/j.ijcard.2023.131554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 09/22/2023] [Accepted: 10/19/2023] [Indexed: 10/26/2023]
Abstract
BACKGROUND There is a lack of predictive biomarkers for the onset or activity of protein-losing enteropathy (PLE), a Fontan procedure-associated complication. Here, we aimed to identify the gut microbiota composition of patients with active PLE and investigate its relationship with PLE activity. METHODS This multicenter case-control study involved patients who developed PLE (n = 16) after the Fontan procedure and those who did not (non-PLE; n = 20). Patients with PLE who maintained a serum albumin level of ≥3 g/dL for >1 year were included in the remissive-stage-PLE group (n = 9) and those who did not maintain this level were included in the active-PLE group (n = 7). 16S rRNA gene sequencing analysis of fecal samples was performed using QIIME2 pipeline. Alpha (Shannon and Faith's phylogenetic diversity indices) and beta diversity was assessed using principal coordinate analysis based on unweighted UniFrac distances. RESULTS Shannon and Faith's phylogenetic diversity indices were lower in the active-PLE group than in the remissive-stage- (q = 0.028 and 0.025, respectively) and non-PLE (q = 0.028 and 0.017, respectively) groups. Analysis of beta diversity revealed a difference in the microbiota composition between the active-PLE and the other two groups. Linear discriminant effect size analysis demonstrated differences in the relative abundance of Bifidobacterium and Granulicatella spp., and Ruminococcus torques between patients with active- and those with remissive-stage-PLE. CONCLUSIONS Gut microbiota dysbiosis was observed in patients with active PLE. Changes in the bacterial composition of the gut microbiota and decreased diversity may be associated with the severity of PLE.
Collapse
Affiliation(s)
- Kiyotaka Go
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kazuhiro Horiba
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
| | - Hidenori Yamamoto
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshihito Morimoto
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshie Fukasawa
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Naoki Ohashi
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Pediatric Cardiology, Japan Community Healthcare Organization Chukyo Hospital, Nagoya, Japan
| | - Kazushi Yasuda
- Department of Pediatric Cardiology, Aichi Children's Health and Medical Center, Obu, Japan
| | - Yuichi Ishikawa
- Department of Pediatric Cardiology, Fukuoka Children's Hospital, Fukuoka, Japan
| | - Kenji Kuraishi
- Department of Pediatric Cardiology and Neonatology, Ogaki Municipal Hospital, Gifu, Japan
| | - Kazutaka Suzuki
- Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yoshinori Ito
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
| | - Yoshiyuki Takahashi
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Taichi Kato
- Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
| |
Collapse
|
20
|
Florio M, Crudele L, Moschetta A, Gadaleta RM. Discovering the Nutrition-Microbiota Interplay in Inflammatory Bowel Disease: Are We There Yet? Endocrinology 2024:333-371. [DOI: 10.1007/978-3-031-35064-1_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
21
|
Pandey H, Jain D, Tang DWT, Wong SH, Lal D. Gut microbiota in pathophysiology, diagnosis, and therapeutics of inflammatory bowel disease. Intest Res 2024; 22:15-43. [PMID: 37935653 PMCID: PMC10850697 DOI: 10.5217/ir.2023.00080] [Citation(s) in RCA: 23] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 08/23/2023] [Accepted: 08/27/2023] [Indexed: 11/09/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a multifactorial disease, which is thought to be an interplay between genetic, environment, microbiota, and immune-mediated factors. Dysbiosis in the gut microbial composition, caused by antibiotics and diet, is closely related to the initiation and progression of IBD. Differences in gut microbiota composition between IBD patients and healthy individuals have been found, with reduced biodiversity of commensal microbes and colonization of opportunistic microbes in IBD patients. Gut microbiota can, therefore, potentially be used for diagnosing and prognosticating IBD, and predicting its treatment response. Currently, there are no curative therapies for IBD. Microbiota-based interventions, including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, have been recognized as promising therapeutic strategies. Clinical studies and studies done in animal models have provided sufficient evidence that microbiota-based interventions may improve inflammation, the remission rate, and microscopic aspects of IBD. Further studies are required to better understand the mechanisms of action of such interventions. This will help in enhancing their effectiveness and developing personalized therapies. The present review summarizes the relationship between gut microbiota and IBD immunopathogenesis. It also discusses the use of gut microbiota as a noninvasive biomarker and potential therapeutic option.
Collapse
Affiliation(s)
| | | | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi, India
| |
Collapse
|
22
|
Jadhav A, Jagtap S, Vyavahare S, Sharbidre A, Kunchiraman B. Reviewing the potential of probiotics, prebiotics and synbiotics: advancements in treatment of ulcerative colitis. Front Cell Infect Microbiol 2023; 13:1268041. [PMID: 38145046 PMCID: PMC10739422 DOI: 10.3389/fcimb.2023.1268041] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/22/2023] [Indexed: 12/26/2023] Open
Abstract
Inflammatory bowel diseases (IBD) like Crohn's and ulcerative colitis (UC) are multifactorial pathologies caused by environmental factors and genetic background. UC is a chronic inflammatory disorder that specifically targets the colon, resulting in inflammation. Various chemical interventions, including aminosalicylates, corticosteroids, immunomodulators, and biological therapies, have been extensively employed for the purpose of managing symptoms associated with UC. Nevertheless, it is important to note that these therapeutic interventions may give rise to undesirable consequences, including, but not limited to, the potential for weight gain, fluid retention, and heightened vulnerability to infections. Emerging therapeutic approaches for UC are costly due to their chronic nature. Alternatives like synbiotic therapy, combining prebiotics and probiotics, have gained attention for mitigating dysbiosis in UC patients. Prebiotics promote beneficial bacteria proliferation, while probiotics establish a balanced gut microbiota and regulate immune system functionality. The utilisation of synbiotics has been shown to improve the inflammatory response and promote the resolution of symptoms in individuals with UC through the stimulation of beneficial bacteria growth and the enhancement of intestinal barrier integrity. Hence, this review article aims to explore the potential benefits and underlying reasons for incorporating alternative approaches in the management of UC with studies performed using prebiotics, probiotics, and synbiotics to treat ulcerative colitis and to highlight safety and considerations in UC and future perspectives. This will facilitate the utilisation of novel treatment strategies for the safer and more efficacious management of patients with UC.
Collapse
Affiliation(s)
- Apurva Jadhav
- Herbal Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Suresh Jagtap
- Herbal Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Suresh Vyavahare
- Sai Ayurved Medical College, Maharashtra University of Health Sciences, Solapur, Maharashtra, India
| | - Archana Sharbidre
- Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India
| | - Bipinraj Kunchiraman
- Microbial Biotechnology, Rajiv Gandhi Institute of IT & Biotechnology, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| |
Collapse
|
23
|
Zheng C, Zhong Y, Xie J, Wang Z, Zhang W, Pi Y, Zhang W, Liu L, Luo J, Xu W. Bacteroides acidifaciens and its derived extracellular vesicles improve DSS-induced colitis. Front Microbiol 2023; 14:1304232. [PMID: 38098663 PMCID: PMC10720640 DOI: 10.3389/fmicb.2023.1304232] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 11/13/2023] [Indexed: 12/17/2023] Open
Abstract
Introduction "Probiotic therapy" to regulate gut microbiota and intervene in intestinal diseases such as inflammatory bowel disease (IBD) has become a research hotspot. Bacteroides acidifaciens, as a new generation of probiotics, has shown beneficial effects on various diseases. Methods In this study, we utilized a mouse colitis model induced by dextran sodium sulfate (DSS) to investigate how B. acidifaciens positively affects IBD. We evaluated the effects ofB. acidifaciens, fecal microbiota transplantation, and bacterial extracellular vesicles (EVs) on DSS-induced colitis in mice. We monitored the phenotype of mouse colitis, detected serum inflammatory factors using ELISA, evaluated intestinal mucosal barrier function using Western blotting and tissue staining, evaluated gut microbiota using 16S rRNA sequencing, and analyzed differences in EVs protein composition derived from B. acidifaciens using proteomics to explore how B. acidifaciens has a positive impact on mouse colitis. Results We confirmed that B. acidifaciens has a protective effect on colitis, including alleviating the colitis phenotype, reducing inflammatory response, and improving intestinal barrier function, accompanied by an increase in the relative abundance of B. acidifaciens and Ruminococcus callidus but a decrease in the relative abundance of B. fragilis. Further fecal bacterial transplantation or fecal filtrate transplantation confirmed the protective effect of eosinophil-regulated gut microbiota and metabolites on DSS-induced colitis. Finally, we validated that EVs derived from B. acidifaciens contain rich functional proteins that can contribute to the relief of colitis. Conclusion Therefore, B. acidifaciens and its derived EVs can alleviate DSS-induced colitis by reducing mucosal damage to colon tissue, reducing inflammatory response, promoting mucosal barrier repair, restoring gut microbiota diversity, and restoring gut microbiota balance in mice. The results of this study provide a theoretical basis for the preclinical application of the new generation of probiotics.
Collapse
Affiliation(s)
- Cihua Zheng
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Institute of Translational Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, China
| | - Yuchun Zhong
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jian Xie
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhuoya Wang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Wenming Zhang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yiming Pi
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Wenjun Zhang
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Li Liu
- Graduate School of Jiangxi University of Chinese Medicine, Nanchang, China
| | - Jun Luo
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Institute of Translational Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, China
| | - Wei Xu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Institute of Translational Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi, China
| |
Collapse
|
24
|
Shin Y, Han S, Kwon J, Ju S, Choi TG, Kang I, Kim SS. Roles of Short-Chain Fatty Acids in Inflammatory Bowel Disease. Nutrients 2023; 15:4466. [PMID: 37892541 PMCID: PMC10609902 DOI: 10.3390/nu15204466] [Citation(s) in RCA: 71] [Impact Index Per Article: 35.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 10/19/2023] [Accepted: 10/19/2023] [Indexed: 10/29/2023] Open
Abstract
The gut microbiome is a diverse bacterial community in the human gastrointestinal tract that plays important roles in a variety of biological processes. Short-chain fatty acids (SCFA) are produced through fermentation of dietary fiber. Certain microbes in the gut are responsible for producing SCFAs such as acetate, propionate and butyrate. An imbalance in gut microbiome diversity can lead to metabolic disorders and inflammation-related diseases. Changes in SCFA levels and associated microbiota were observed in IBD, suggesting an association between SCFAs and disease. The gut microbiota and SCFAs affect reactive oxygen species (ROS) associated with IBD. Gut microbes and SCFAs are closely related to IBD, and it is important to study them further.
Collapse
Affiliation(s)
- Yoonhwa Shin
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (S.H.); (J.K.); (S.J.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Sunhee Han
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (S.H.); (J.K.); (S.J.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Juhui Kwon
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (S.H.); (J.K.); (S.J.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Songhyun Ju
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (S.H.); (J.K.); (S.J.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Tae Gyu Choi
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Insug Kang
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (S.H.); (J.K.); (S.J.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| | - Sung Soo Kim
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea; (Y.S.); (S.H.); (J.K.); (S.J.)
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea;
- Biomedical Science Institute, Kyung Hee University, Seoul 02447, Republic of Korea
| |
Collapse
|
25
|
Wu Z, He J, Zhang Z, Li J, Zou H, Tan X, Wang Y, Yao Y, Xiong W. Propionic Acid Driven by the Lactobacillus johnsonii Culture Supernatant Alleviates Colitis by Inhibiting M1 Macrophage Polarization by Modulating the MAPK Pathway in Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:14951-14966. [PMID: 37788400 DOI: 10.1021/acs.jafc.3c00278] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2023]
Abstract
In this study, we investigated the effects of Lactobacillus johnsonii on the mouse colitis model. The results showed that the supernatant of the L. johnsonii culture alleviated colitis and remodeled gut microbiota, represented by an increased abundance of bacteria producing short-chain fatty acids, leading to an increased concentration of propionic acid in the intestine. Further studies revealed that propionic acid inhibited activation of the MAPK signaling pathway and polarization of M1 macrophages. Macrophage clearance assays confirmed that macrophages are indispensable for alleviating colitis through propionic acid. In vitro experiments showed that propionic acid directly inhibited the MAPK signaling pathway in macrophages and reduced M1 macrophage polarization, thereby inhibiting the secretion of pro-inflammatory cytokines. These findings improve our understanding of how L. johnsonii attenuates inflammatory bowel disease (IBD) and provide valuable insights for identifying molecular targets for IBD treatment in the future.
Collapse
Affiliation(s)
- Zhifeng Wu
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Jinhui He
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Zeyue Zhang
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Jingjing Li
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Huicong Zou
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Xiang Tan
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Yuqing Wang
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Yong Yao
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| | - Wen Xiong
- College of Animal Sciences and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China
| |
Collapse
|
26
|
Rayyan YM, Agraib LM, Alkhatib B, Yamani MI, Abu-Sneineh AT, Tayyem RF. Does probiotic supplementation improve quality of life in mild-to-moderately active ulcerative colitis patients in Jordan? A secondary outcome of the randomized, double-blind, placebo-controlled study. Eur J Nutr 2023; 62:3069-3077. [PMID: 37498369 DOI: 10.1007/s00394-023-03207-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 07/10/2023] [Indexed: 07/28/2023]
Abstract
PURPOSE Recent findings revealed a potential effect of a probiotic in improving quality of life (QoL) in ulcerative colitis (UC). In Jordan, there is scarce data about UC patients and QoL. METHODS Twenty-four UC patients were included in the study and were randomly allocated into probiotic (3 × 1010 probiotic capsules containing nine Lactobacillus and five Bifidobacterium species) and placebo control groups (containing polysaccharide supplied in an identical bottle) 3 times daily/6 weeks. A short inflammatory bowel disease questionnaire (SIBDQ) was used to assess the change in the quality of life in both groups at the beginning and the end of the intervention; The study was completed during the COVID-19 pandemic. RESULTS Patients treated with probiotics showed a higher score of social (6.92 ± 0.29, p = 0.019), bowel (6.31 ± 0.46, p = 0.001), emotional (6.47 ± 0.46, p < 0.001), and total SIBDQ scores (6.54 ± 0.29, p < 0.001) compared to the placebo group (5.75 ± 1.57, 4.72 ± 1.34, 4.42 ± 1.67 and 4.96 ± 1.27; respectively). Also, the probiotic group had significantly better scores in the systemic, social, bowel, emotional, and total SIBDQ scores in terms of pre- to post-treatment (p < 0.001). CONCLUSIONS The use of probiotic therapy containing Lactobacillus and Bifidobacterium species had significantly improved the quality of life among UC patients, this was shown by the improvement in the scores of the systemic domain, social domain, bowel domain, emotional domain, and total SIBDQ. This study is part of a registered study at ClinicalTrials.gov with the number NCT04223479.
Collapse
Affiliation(s)
- Yaser Mohammed Rayyan
- Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, The University of Jordan, Amman, Jordan.
| | - Lana M Agraib
- Department of Food Science and Nutrition, Faculty of Agriculture, Jerash University, Jerash, Jordan
| | - Buthaina Alkhatib
- Department of Clinical Nutrition and Dietetics, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa, Jordan
| | - Mohammed I Yamani
- Department of Nutrition and Food Technology, Faculty of Agriculture, The University of Jordan, Amman, Jordan
| | - Awni Taleb Abu-Sneineh
- Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, The University of Jordan, Amman, Jordan
| | - Reema F Tayyem
- Department of Nutrition and Food Technology, Faculty of Agriculture, The University of Jordan, Amman, Jordan
- Department of Human Nutrition, College of Health Sciences, Qatar University, Doha, Qatar
| |
Collapse
|
27
|
Latif A, Shehzad A, Niazi S, Zahid A, Ashraf W, Iqbal MW, Rehman A, Riaz T, Aadil RM, Khan IM, Özogul F, Rocha JM, Esatbeyoglu T, Korma SA. Probiotics: mechanism of action, health benefits and their application in food industries. Front Microbiol 2023; 14:1216674. [PMID: 37664108 PMCID: PMC10470842 DOI: 10.3389/fmicb.2023.1216674] [Citation(s) in RCA: 155] [Impact Index Per Article: 77.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 08/04/2023] [Indexed: 09/05/2023] Open
Abstract
Probiotics, like lactic acid bacteria, are non-pathogenic microbes that exert health benefits to the host when administered in adequate quantity. Currently, research is being conducted on the molecular events and applications of probiotics. The suggested mechanisms by which probiotics exert their action include; competitive exclusion of pathogens for adhesion sites, improvement of the intestinal mucosal barrier, gut immunomodulation, and neurotransmitter synthesis. This review emphasizes the recent advances in the health benefits of probiotics and the emerging applications of probiotics in the food industry. Due to their capability to modulate gut microbiota and attenuate the immune system, probiotics could be used as an adjuvant in hypertension, hypercholesterolemia, cancer, and gastrointestinal diseases. Considering the functional properties, probiotics are being used in the dairy, beverage, and baking industries. After developing the latest techniques by researchers, probiotics can now survive within harsh processing conditions and withstand GI stresses quite effectively. Thus, the potential of probiotics can efficiently be utilized on a commercial scale in food processing industries.
Collapse
Affiliation(s)
- Anam Latif
- Department of Human Nutrition and Dietetics, School of Food and Agricultural Sciences, University of Management and Technology, Lahore, Pakistan
| | - Aamir Shehzad
- UniLaSalle, Univ. Artois, ULR7519 - Transformations & Agro-resources, Normandie Université, Mont-Saint-Aignan, France
| | - Sobia Niazi
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China
| | - Asna Zahid
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | - Waqas Ashraf
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, China
| | - Muhammad Waheed Iqbal
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Abdur Rehman
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Tahreem Riaz
- School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu, China
| | - Rana Muhammad Aadil
- National Institute of Food Science and Technology, University of Agriculture, Faisalabad, Pakistan
| | - Imran Mahmood Khan
- College of Food and Biological Engineering, Jimei University, Xiamen, China
| | - Fatih Özogul
- Department of Seafood Processing Technology, Faculty of Fisheries, Cukurova University, Adana, Türkiye
- Biotechnology Research and Application Center, Cukurova University, Adana, Türkiye
| | - João Miguel Rocha
- CBQF - Centro de Biotecnologia e Química Fina – Laboratório Associado, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Porto, Portugal
- LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
- ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Porto, Portugal
| | - Tuba Esatbeyoglu
- Department of Food Development and Food Quality, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Hannover, Germany
| | - Sameh A. Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, Egypt
- School of Food Science and Engineering, South China University of Technology, Guangzhou, China
| |
Collapse
|
28
|
Ye Z, Yang X, Deng B, Liao Z, Fang X, Wang J. Prevention of DSS-induced colitis in mice with water kefir microbiota via anti-inflammatory and microbiota-balancing activity. Food Funct 2023. [PMID: 37449473 DOI: 10.1039/d3fo00354j] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2023]
Abstract
Water kefir, a natural and stable functional microbiota system consisting of a symbiotic mixture of probiotics, shows multiple bioactivities but little is known about the effect of water kefir microbiota on the prevention of inflammatory bowel disease (IBD), which is one of the most common intestinal problems and has become a worldwide public health concern. Here, the main objectives of the present study were to investigate the preventative effects of water kefir microbiota, a probiotic consortium mainly consisting of bacteria belonging to Acetobacter, Lactobacillus, and Komagataeibacter and fungi belonging to Saccharomyces and Talaromyces, in a dextran sodium sulfate (DSS)-induced colitis mouse model and unveil the underlying mechanism of the action. Water kefir microbiota effectively improved the disease severity of DSS-induced colitis, including decreased body weight and colon length, increased spleen index and DAI score, and colonic tissue damage. Moreover, water kefir microbiota restored the abnormal expression of tight junction proteins (such as occludin, ZO-1, and claudin-1) and pro-inflammatory and anti-inflammatory cytokines (such as IL-1β, IL-6, TNF-α, COX-2, iNOS, and IL-10) and inactivated TLR4-MyD88-NF-κB pathway induced by DSS. Water kefir microbiota also improved the composition and metabolism of intestinal microbiota. These findings demonstrated that water kefir microbiota could exert protective roles in the DSS-induced colitis mouse model by reducing inflammation and regulating microbial dysbiosis, which will be helpful for the development of water kefir microbiota-based microbial products as an alternative preventative strategy for IBD.
Collapse
Affiliation(s)
- Zhimin Ye
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
- Guangzhou Laboratory, Guangzhou 510005, China
| | - Ximiao Yang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
| | - Boxiong Deng
- State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510000, China
| | - Zhenlin Liao
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
| | - Xiang Fang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
| | - Jie Wang
- Guangdong Provincial Key Laboratory of Nutraceuticals and Functional Foods, Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
| |
Collapse
|
29
|
Martyniak A, Zakrzewska Z, Schab M, Zawartka A, Wędrychowicz A, Skoczeń S, Tomasik PJ. Prevention and Health Benefits of Prebiotics, Probiotics and Postbiotics in Acute Lymphoblastic Leukemia. Microorganisms 2023; 11:1775. [PMID: 37512947 PMCID: PMC10384688 DOI: 10.3390/microorganisms11071775] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Revised: 06/04/2023] [Accepted: 07/06/2023] [Indexed: 07/30/2023] Open
Abstract
Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children, comprising 75-85% of cases. Aggressive treatment of leukemias includes chemotherapy and antibiotics that often disrupt the host microbiota. Additionally, the gut microbiota may play a role in the development and progression of acute leukemia. Prebiotics, probiotics, and postbiotics are considered beneficial to health. The role of prebiotics in the treatment and development of leukemia is not well understood, but inulin can be potentially used in the treatment of leukemia. Some probiotic bacteria such as Lactobacillus shows anticancer activity in in vitro studies. Additionally, Bifidobacterium spp., as a consequence of the inhibition of growth factor signaling and mitochondrial-mediated apoptosis, decrease the proliferation of cancer cells. Many bacterial metabolites have promising anticancer potential. The available research results are promising. However, more research is needed in humans, especially in the child population, to fully understand the relationship between the gut microbiota and acute leukemia.
Collapse
Affiliation(s)
- Adrian Martyniak
- Department of Clinical Biochemistry, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Zuzanna Zakrzewska
- Department of Pediatric Oncology and Hematology, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Magdalena Schab
- Department of Pediatric Oncology and Hematology, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Aleksandra Zawartka
- Department of Paediatrics, Gastroenterology and Nutrition, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Andrzej Wędrychowicz
- Department of Paediatrics, Gastroenterology and Nutrition, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Szymon Skoczeń
- Department of Pediatric Oncology and Hematology, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| | - Przemysław J Tomasik
- Department of Clinical Biochemistry, Pediatric Institute, Faculty of Medicine, Jagiellonian University Medical College, 30-663 Krakow, Poland
| |
Collapse
|
30
|
Huang C, Hao W, Wang X, Zhou R, Lin Q. Probiotics for the treatment of ulcerative colitis: a review of experimental research from 2018 to 2022. Front Microbiol 2023; 14:1211271. [PMID: 37485519 PMCID: PMC10358780 DOI: 10.3389/fmicb.2023.1211271] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 06/22/2023] [Indexed: 07/25/2023] Open
Abstract
Ulcerative colitis (UC) has become a worldwide public health problem, and the prevalence of the disease among children has been increasing. The pathogenesis of UC has not been elucidated, but dysbiosis of the gut microbiota is considered the main cause of chronic intestinal inflammation. This review focuses on the therapeutic effects of probiotics on UC and the potential mechanisms involved. In animal studies, probiotics have been shown to alleviate symptoms of UC, including weight loss, diarrhea, blood in the stool, and a shortened colon length, while also restoring intestinal microecological homeostasis, improving gut barrier function, modulating the intestinal immune response, and attenuating intestinal inflammation, thereby providing theoretical support for the development of probiotic-based microbial products as an adjunctive therapy for UC. However, the efficacy of probiotics is influenced by factors such as the bacterial strain, dose, and form. Hence, the mechanisms of action need to be investigated further. Relevant clinical trials are currently lacking, so the extension of animal experimental findings to clinical application requires a longer period of consideration for validation.
Collapse
Affiliation(s)
- Cuilan Huang
- Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Children’s Hospital, Wuxi, China
| | - Wujuan Hao
- Department of Digestive, Affiliated Children’s Hospital of Jiangnan University, Wuxi, China
| | - Xuyang Wang
- Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Children’s Hospital, Wuxi, China
| | - Renmin Zhou
- Department of Digestive, Affiliated Children’s Hospital of Jiangnan University, Wuxi, China
| | - Qiong Lin
- Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi Children’s Hospital, Wuxi, China
| |
Collapse
|
31
|
Li Q, Zheng T, Ding H, Chen J, Li B, Zhang Q, Yang S, Zhang S, Guan W. Exploring the Benefits of Probiotics in Gut Inflammation and Diarrhea-From an Antioxidant Perspective. Antioxidants (Basel) 2023; 12:1342. [PMID: 37507882 PMCID: PMC10376667 DOI: 10.3390/antiox12071342] [Citation(s) in RCA: 20] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 06/17/2023] [Accepted: 06/19/2023] [Indexed: 07/30/2023] Open
Abstract
Inflammatory bowel disease (IBD), characterized by an abnormal immune response, includes two distinct types: Crohn's disease (CD) and ulcerative colitis (UC). Extensive research has revealed that the pathogeny of IBD encompasses genetic factors, environmental factors, immune dysfunction, dysbiosis, and lifestyle choices. Furthermore, patients with IBD exhibit both local and systemic oxidative damage caused by the excessive presence of reactive oxygen species. This oxidative damage exacerbates immune response imbalances, intestinal mucosal damage, and dysbiosis in IBD patients. Meanwhile, the weaning period represents a crucial phase for pigs, during which they experience pronounced intestinal immune and inflammatory responses, leading to severe diarrhea and increased mortality rates. Pigs are highly similar to humans in terms of physiology and anatomy, making them a potential choice for simulating human IBD. Although the exact mechanism behind IBD and post-weaning diarrhea remains unclear, the oxidative damage, in its progression and pathogenesis, is well acknowledged. Besides conventional anti-inflammatory drugs, certain probiotics, particularly Lactobacillus and Bifidobacteria strains, have been found to possess antioxidant properties. These include the scavenging of reactive oxygen species, chelating metal ions to inhibit the Fenton reaction, and the regulation of host antioxidant enzymes. Consequently, numerous studies in the last two decades have committed to exploring the role of probiotics in alleviating IBD. Here, we sequentially discuss the oxidative damage in IBD and post-weaning diarrhea pathogenesis, the negative consequences of oxidative stress on IBD, the effectiveness of probiotics in IBD treatment, the application of probiotics in weaned piglets, and the potential antioxidant mechanisms of probiotics.
Collapse
Affiliation(s)
- Qihui Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Tenghui Zheng
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Hanting Ding
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Jiaming Chen
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Baofeng Li
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Qianzi Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Siwang Yang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
| | - Shihai Zhang
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
- College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China
- Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China
| | - Wutai Guan
- Guangdong Province Key Laboratory of Animal Nutrition Control, College of Animal Science, South China Agricultural University, Guangzhou 510642, China
- College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China
- Guangdong Laboratory for Lingnan Modern Agriculture, South China Agricultural University, Guangzhou 510642, China
| |
Collapse
|
32
|
Li S, Xu K, Cheng Y, Chen L, Yi A, Xiao Z, Zhao X, Chen M, Tian Y, Meng W, Tang Z, Zhou S, Ruan G, Wei Y. The role of complex interactions between the intestinal flora and host in regulating intestinal homeostasis and inflammatory bowel disease. Front Microbiol 2023; 14:1188455. [PMID: 37389342 PMCID: PMC10303177 DOI: 10.3389/fmicb.2023.1188455] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 05/10/2023] [Indexed: 07/01/2023] Open
Abstract
Pharmacological treatment of inflammatory bowel disease (IBD) is inefficient and difficult to discontinue appropriately, and enterobacterial interactions are expected to provide a new target for the treatment of IBD. We collected recent studies on the enterobacterial interactions among the host, enterobacteria, and their metabolite products and discuss potential therapeutic options. Intestinal flora interactions in IBD are affected in the reduced bacterial diversity, impact the immune system and are influenced by multiple factors such as host genetics and diet. Enterobacterial metabolites such as SCFAs, bile acids, and tryptophan also play important roles in enterobacterial interactions, especially in the progression of IBD. Therapeutically, a wide range of sources of probiotics and prebiotics exhibit potential therapeutic benefit in IBD through enterobacterial interactions, and some have gained wide recognition as adjuvant drugs. Different dietary patterns and foods, especially functional foods, are novel therapeutic modalities that distinguish pro-and prebiotics from traditional medications. Combined studies with food science may significantly improve the therapeutic experience of patients with IBD. In this review, we provide a brief overview of the role of enterobacteria and their metabolites in enterobacterial interactions, discuss the advantages and disadvantages of the potential therapeutic options derived from such metabolites, and postulate directions for further research.
Collapse
Affiliation(s)
- Siyu Li
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Basic Medicine College of Army Medical University, Army Medical University, Chongqing, China
| | - Kan Xu
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Basic Medicine College of Army Medical University, Army Medical University, Chongqing, China
| | - Yi Cheng
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Lu Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Ailin Yi
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zhifeng Xiao
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Xuefei Zhao
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Minjia Chen
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yuting Tian
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Wei Meng
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Zongyuan Tang
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shuhong Zhou
- Department of Laboratory Animal Center, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Guangcong Ruan
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yanling Wei
- Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| |
Collapse
|
33
|
Hasan N, Yang H. Evaluation of microbial and vancomycin treatments in ulcerative colitis in murine models. PLoS One 2023; 18:e0285613. [PMID: 37167242 PMCID: PMC10174502 DOI: 10.1371/journal.pone.0285613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Accepted: 04/26/2023] [Indexed: 05/13/2023] Open
Abstract
BACKGROUND Despite the number of available therapies for ulcerative colitis (UC), severe side effects and high cost has limited their clinical application. Thus, finding new alternative strategies with minimal side effects is inevitable. Therefore, this study aimed to compare the effectiveness of different therapeutic approaches in DSS-induced colitis. METHODS Firstly, we designed oral bio-therapeutic products, Live Bacterial Products (LBP), which include a mixture of fecal bacteria strains isolated from healthy mice and prepared by microencapsulation and freeze-dried techniques. Then we investigated the efficiency of 7 days of freeze-dried FMT, LBP, and vancomycin treatments in DSS-induced colitis. Secondly, we compared the effect of 15 days of microbial therapies (freeze-dried powder of FMT and LBP microcapsules) and seven days of oral vancomycin on the severity of colitis in mice. Furthermore, the levels of IL-1β and TNF-α were measured in serum by ELISA, and the fecal microbiota diversity was analyzed by high-throughput sequencing for all mice groups. RESULTS After seven days of treatments, our results indicated that oral vancomycin reduced the severity of DSS-induced colitis in mice, where weight gain and a decrease in IL-1 β and TNF-α levels were observed in the vancomycin group compared with other treatment groups. While after two weeks of treatment, the LBP microcapsules were able to reduce the severity of colitis. And at the end of the treatment period, weight gain and a decrease in the DAI scores and the levels of IL-1β and TNF-α were noted in the LBP treatment group compared to other treatment groups. By high-throughput sequencing of the 16S rRNA gene, our results showed that while the microcapsules LBP treatment increased the fecal microbial diversity, after vancomycin therapy, most of the fecal microbiota genera and operational taxonomic units (OTUs) were depleted. CONCLUSION Our results concluded that treatment duration and preparation methods affect the microbial therapies' efficiency in UC. Furthermore, this study highlighted the negative consequences of oral vancomycin administration on gut health that should be known before using this medication.
Collapse
Affiliation(s)
- Nihal Hasan
- Department of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, People’s Republic of China
- Faculty of Health Science, Al-Baath University, Homs, Syria
| | - Hongyi Yang
- Department of Microbiology, Northeast Forestry University, Harbin, Heilongjiang, People’s Republic of China
| |
Collapse
|
34
|
Roy S, Dhaneshwar S. Role of prebiotics, probiotics, and synbiotics in management of inflammatory bowel disease: Current perspectives. World J Gastroenterol 2023; 29:2078-2100. [PMID: 37122604 PMCID: PMC10130969 DOI: 10.3748/wjg.v29.i14.2078] [Citation(s) in RCA: 107] [Impact Index Per Article: 53.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/29/2022] [Accepted: 03/21/2023] [Indexed: 04/13/2023] Open
Abstract
Experimental evidence supports the fact that changes in the bowel microflora due to environmental or dietary factors have been investigated as implicating factors in the etiopathogenesis of inflammatory bowel disease (IBD). The amassing knowledge that the inhabited microbiome regulates the gut physiology and immune functions in IBD, has led researchers to explore the effectiveness of prebiotics, probiotics, and synbiotics in treating IBD. This therapeutic approach focuses on restoring the dynamic balance between the microflora and host defense mechanisms in the intestinal mucosa to prevent the onset and persistence of intestinal inflammation. Numerous microbial strains and carbohydrate blends, along with their combinations have been examined in experimental colitis models and clinical trials, and the results indicated that it can be an attractive therapeutic strategy for the suppression of inflammation, remission induction, and relapse prevention in IBD with minimal side effects. Several mechanisms of action of probiotics (for e.g., Lactobacillus species, and Bifidobacterium species) have been reported such as suppression of pathogen growth by releasing certain antimicrobial mediators (lactic and hydrogen peroxide, acetic acid, and bacteriocins), immunomodulation and initiation of an immune response, enhancement of barrier activity, and suppression of human T-cell proliferation. Prebiotics such as lactulose, lactosucrose, oligofructose, and inulin have been found to induce the growth of certain types of host microflora, resulting in an enriched enteric function. These non-digestible food dietary components have been reported to exert anti-inflammatory effects by inhibiting the expression of tumor necrosis factor-α-related cytokines while augmenting interleukin-10 levels. Although pro-and prebiotics has established their efficacy in healthy subjects, a better understanding of the luminal ecosystem is required to determine which specific bacterial strain or combination of probiotics and prebiotics would prove to be the ideal treatment for IBD. Clinical trials, however, have given some conflicting results, requiring the necessity to cite the more profound clinical effect of these treatments on IBD remission and prevention. The purpose of this review article is to provide the most comprehensive and updated review on the utility of prebiotics, probiotics, and synbiotics in the management of active Crohn's disease and ulcerative colitis/pouchitis.
Collapse
Affiliation(s)
- Supriya Roy
- Amity Institute of Pharmacy, Lucknow, Amity University Uttar Pradesh, Sector 125, Noida 201313, Uttar Pradesh, India
| | - Suneela Dhaneshwar
- Amity Institute of Pharmacy, Amity University Maharashtra, Mumbai 410206, Maharashtra, India
| |
Collapse
|
35
|
Bischoff SC, Bager P, Escher J, Forbes A, Hébuterne X, Hvas CL, Joly F, Klek S, Krznaric Z, Ockenga J, Schneider S, Shamir R, Stardelova K, Bender DV, Wierdsma N, Weimann A. ESPEN guideline on Clinical Nutrition in inflammatory bowel disease. Clin Nutr 2023; 42:352-379. [PMID: 36739756 DOI: 10.1016/j.clnu.2022.12.004] [Citation(s) in RCA: 114] [Impact Index Per Article: 57.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 12/05/2022] [Indexed: 01/15/2023]
Abstract
The present guideline is an update and extension of the ESPEN scientific guideline on Clinical Nutrition in Inflammatory Bowel Disease published first in 2017. The guideline has been rearranged according to the ESPEN practical guideline on Clinical Nutrition in Inflammatory Bowel Disease published in 2020. All recommendations have been checked and, if needed, revised based on new literature, before they underwent the ESPEN consensus procedure. Moreover, a new chapter on microbiota modulation as a new option in IBD treatment has been added. The number of recommendations has been increased to 71 recommendations in the guideline update. The guideline is aimed at professionals working in clinical practice, either in hospitals or in outpatient medicine, and treating patients with IBD. General aspects of care in patients with IBD, and specific aspects during active disease and in remission are addressed. All recommendations are equipped with evidence grades, consensus rates, short commentaries and links to cited literature.
Collapse
Affiliation(s)
- Stephan C Bischoff
- Institute of Nutritional Medicine, University of Hohenheim, Stuttgart, Germany.
| | - Palle Bager
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
| | - Johanna Escher
- Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.
| | - Alastair Forbes
- Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
| | - Xavier Hébuterne
- Department of Gastroenterology and Clinical Nutrition, CHU of Nice, University Côte d'Azur, Nice, France.
| | - Christian Lodberg Hvas
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
| | - Francisca Joly
- Department of Gastroenterology and Nutrition Support, CHU de Beaujon, APHP, University of Paris, Paris, France.
| | - Stansilaw Klek
- Surgical Oncology Clinic, Maria Sklodowska-Curie National Cancer Institute, Krakow, Poland.
| | - Zeljko Krznaric
- Department of Gastroenterology, Hepatology and Nutrition, University Hospital Centre Zagreb, University of Zagreb, Croatia.
| | - Johann Ockenga
- Medizinische Klinik II, Klinikum Bremen-Mitte, Bremen FRG, Bremen, Germany.
| | - Stéphane Schneider
- Department of Gastroenterology and Clinical Nutrition, CHU de Nice, University Côte d'Azur, Nice, France.
| | - Raanan Shamir
- Institute for Gastroenterology, Nutrition and Liver Diseases, Schneider Children's Medical Center of Israel, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
| | - Kalina Stardelova
- University Clinic for Gastroenterohepatology, Clinical Campus "Mother Theresa", University St Cyrul and Methodius, Skopje, North Macedonia.
| | - Darija Vranesic Bender
- Unit of Clinical Nutrition, Department of Internal Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
| | - Nicolette Wierdsma
- Department of Nutrition and Dietetics, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
| | - Arved Weimann
- Department of General, Visceral and Oncological Surgery, St. George Hospital, Leipzig, Germany.
| |
Collapse
|
36
|
di Vito R, Di Mezza A, Conte C, Traina G. The Crosstalk between Intestinal Epithelial Cells and Mast Cells Is Modulated by the Probiotic Supplementation in Co-Culture Models. Int J Mol Sci 2023; 24:ijms24044157. [PMID: 36835568 PMCID: PMC9963420 DOI: 10.3390/ijms24044157] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 02/14/2023] [Accepted: 02/17/2023] [Indexed: 02/22/2023] Open
Abstract
The intestinal epithelium constitutes a selectively permeable barrier between the internal and external environment that allows the absorption of nutrients, electrolytes, and water, as well as an effective defense against intraluminal bacteria, toxins, and potentially antigenic material. Experimental evidence suggest that intestinal inflammation is critically dependent on an imbalance of homeostasis between the gut microbiota and the mucosal immune system. In this context, mast cells play a crucial role. The intake of specific probiotic strains can prevent the development of gut inflammatory markers and activation of the immune system. Here, the effect of a probiotic formulation containing L. rhamnosus LR 32, B. lactis BL04, and B. longum BB 536 on intestinal epithelial cells and mast cells was investigated. To mimic the natural host compartmentalization, Transwell co-culture models were set up. Co-cultures of intestinal epithelial cells interfaced with the human mast cell line HMC-1.2 in the basolateral chamber were challenged with lipopolysaccharide (LPS), and then treated with probiotics. In the HT29/HMC-1.2 co-culture, the probiotic formulation was able to counteract the LPS-induced release of interleukin 6 from HMC-1.2, and was effective in preserving the epithelial barrier integrity in the HT29/Caco-2/ HMC-1.2 co-culture. The results suggest the potential therapeutic effect of the probiotic formulation.
Collapse
|
37
|
The Potential Therapeutic Role of Lactobacillaceae rhamnosus for Treatment of Inflammatory Bowel Disease. Foods 2023; 12:foods12040692. [PMID: 36832767 PMCID: PMC9955806 DOI: 10.3390/foods12040692] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/26/2023] [Accepted: 02/01/2023] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a heterogeneous group of diseases associated with chronic inflammation of the intestinal tract, and is highly prevalent worldwide. Although its origin is not yet fully understood, new evidence emphasizes that environmental factors, especially dietary factors and intestinal microbiota disorders are key triggers of IBD. Probiotics, such as Lactobacillaceae spp., play an essential role in human health as they exert beneficial effects on the composition of the human gastrointestinal microbial community and immune system. Probiotic-based therapies have been shown to be effective in alleviating IBD. Among these, Lactobacillaceae rhamnosus is one of the most widely used strains. L. rhamnosus is widely present in the intestines of healthy individuals; it regulates the intestinal immune system and reduces inflammation through a variety of mechanisms. The purpose of this study was to identify scientific evidence related to L. rhamnosus and IBD, review and summarize the results, and discuss the possible mechanisms of action as a starting point for future research on IBD treatment.
Collapse
|
38
|
Lomer MCE, Wilson B, Wall CL. British Dietetic Association consensus guidelines on the nutritional assessment and dietary management of patients with inflammatory bowel disease. J Hum Nutr Diet 2023; 36:336-377. [PMID: 35735908 PMCID: PMC10084145 DOI: 10.1111/jhn.13054] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 06/07/2022] [Indexed: 01/19/2023]
Abstract
BACKGROUND Despite increased awareness of diet and nutrition being integral to the management of patients with inflammatory bowel disease (IBD), there are gaps in the knowledge of IBD healthcare providers regarding nutrition. Furthermore, high quality evidence on nutritional assessment and dietary management of IBD is limited. A Delphi consensus from a panel of experts allows for best-practice guidelines to be developed, especially where high quality evidence is limited. The aim was to develop guidelines for the nutritional assessment and dietary management of IBD using an eDelphi online consensus agreement platform. METHODS Seventeen research topics related to IBD and nutrition were systematically reviewed. Searches in Cochrane, Embase®, Medline® and Scopus® electronic databases were performed. GRADE was used to develop recommendations. Experts from the IBD community (healthcare professionals and patients with IBD) were invited to vote anonymously on the recommendations in a custom-built online platform. Three rounds of voting were carried out with updated iterations of the recommendations and evaluative text based on feedback from the previous round. RESULTS From 23,824 non-duplicated papers, 167 were critically appraised. Fifty-five participants completed three rounds of voting and 14 GRADE statements and 42 practice statements achieved 80% consensus. Comprehensive guidance related to nutrition assessment, nutrition screening and dietary management is provided. CONCLUSIONS Guidelines on the nutritional assessment and dietary management of IBD have been developed using evidence-based consensus to improve equality of care. The statements and practice statements developed demonstrate the level of agreement and the quality and strength of the guidelines.
Collapse
Affiliation(s)
- Miranda C E Lomer
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Nutritional Sciences, King's College London, London, UK
| | - Bridgette Wilson
- Department of Nutrition and Dietetics, Guy's and St Thomas' NHS Foundation Trust, London, UK.,Department of Nutritional Sciences, King's College London, London, UK
| | - Catherine L Wall
- Department of Nutritional Sciences, King's College London, London, UK.,Department of Medicine, University of Otago, Christchurch, New Zealand
| |
Collapse
|
39
|
Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev 2023; 123:31-72. [PMID: 36317983 PMCID: PMC9837825 DOI: 10.1021/acs.chemrev.2c00431] [Citation(s) in RCA: 144] [Impact Index Per Article: 72.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Indexed: 01/12/2023]
Abstract
The human microbiome is composed of a collection of dynamic microbial communities that inhabit various anatomical locations in the body. Accordingly, the coevolution of the microbiome with the host has resulted in these communities playing a profound role in promoting human health. Consequently, perturbations in the human microbiome can cause or exacerbate several diseases. In this Review, we present our current understanding of the relationship between human health and disease development, focusing on the microbiomes found across the digestive, respiratory, urinary, and reproductive systems as well as the skin. We further discuss various strategies by which the composition and function of the human microbiome can be modulated to exert a therapeutic effect on the host. Finally, we examine technologies such as multiomics approaches and cellular reprogramming of microbes that can enable significant advancements in microbiome research and engineering.
Collapse
Affiliation(s)
- Nikhil Aggarwal
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
| | - Shohei Kitano
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
| | - Ginette Ru Ying Puah
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Wilmar
International Limited, Singapore 138568, Singapore
| | - Sandra Kittelmann
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Wilmar
International Limited, Singapore 138568, Singapore
| | - In Young Hwang
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Department
of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
- Singapore
Institute of Technology, Singapore 138683, Singapore
| | - Matthew Wook Chang
- NUS
Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore
- Synthetic
Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456, Singapore
- Wilmar-NUS
(WIL@NUS) Corporate Laboratory, National
University of Singapore, Singapore 117599, Singapore
- Department
of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
| |
Collapse
|
40
|
Li M, Ding J, Stanton C, Ross RP, Zhao J, Yang B, Chen W. Bifidobacterium longum subsp. infantis FJSYZ1M3 ameliorates DSS-induced colitis by maintaining the intestinal barrier, regulating inflammatory cytokines, and modifying gut microbiota. Food Funct 2023; 14:354-368. [PMID: 36511157 DOI: 10.1039/d2fo03263e] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
B. longum subsp. infantis is a subspecies of Bifidobacterium longum, and very few strains are shown to have immunomodulatory effects. In the present study, the improvement of dextran sulphate sodium (DSS)-induced colitis by four B. longum subsp. infantis strains was compared. The results showed that B. longum subsp. infantis FJSYZ1M3 could significantly decrease disease activity index (DAI), inhibit weight loss and colon shortening, and attenuate colon tissue damage in DSS-induced colitis mice. And B. longum subsp. infantis FJSYZ1M3 intervention improved the integrity of intestinal tight junctions, relieved mucus layer damage and inhibited epithelial cell apoptosis, thereby maintaining the intestinal barrier. Additionally, B. longum subsp. infantis FJSYZ1M3 significantly affected the levels of inflammatory cytokines IL-6, IL-1β, and IL-10 in the colon, thus relieving inflammation in colitis mice. Furthermore, B. longum subsp. infantis FJSYZ1M3 could ameliorate gut microbiota disturbance caused by DSS exposure and increase the level of butyric acid in cecal contents. In general, these findings suggested that B. longum subsp. infantis FJSYZ1M3 alleviated DSS-induced colitis by maintaining the intestinal barrier, regulating inflammatory cytokines, and modifying the gut microbiota.
Collapse
Affiliation(s)
- Mingjie Li
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.,School of Food Science and Technology, Jiangnan University, Wuxi, China.
| | - Jiuhong Ding
- Department of Anesthesiology, Wuxi Second People's Hospital, Wuxi, Jiangsu, China.
| | - Catherine Stanton
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China.,APC Microbiome Ireland, University College Cork, Cork, Ireland.,Teagasc Food Research Centre, Moorepark, Co., Cork, Ireland
| | - R Paul Ross
- International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China.,APC Microbiome Ireland, University College Cork, Cork, Ireland
| | - Jianxin Zhao
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.,School of Food Science and Technology, Jiangnan University, Wuxi, China. .,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
| | - Bo Yang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.,School of Food Science and Technology, Jiangnan University, Wuxi, China. .,International Joint Research Laboratory for Pharmabiotics & Antibiotic Resistance, Jiangnan University, Wuxi, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.,School of Food Science and Technology, Jiangnan University, Wuxi, China. .,National Engineering Research Center for Functional Food, Jiangnan University, Wuxi, China
| |
Collapse
|
41
|
Kim JK, Cheon JH. Factors associated with the prescription of probiotics in patients with inflammatory bowel disease: a cross-sectional study. JOURNAL OF YEUNGNAM MEDICAL SCIENCE 2023; 40:37-48. [PMID: 35430792 PMCID: PMC9946923 DOI: 10.12701/jyms.2022.00031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/11/2022] [Accepted: 03/17/2022] [Indexed: 11/04/2022]
Abstract
BACKGRUOUND Commensal bacteria play an important role in the pathogenesis of inflammatory bowel disease (IBD) and probiotics have been used as treatment options. We aimed to explore the current use of probiotics and factors associated with their prescription in patients with IBD. METHODS This cross-sectional study was conducted on a single hospital-based cohort. Patients were eligible if they were ≥18 years old, visited the IBD clinic as an outpatient more than twice during the study period, and had a confirmed diagnosis of IBD. Patients were divided into two groups based on the prescription of probiotics. Clinical assessments were compared between the two groups. RESULTS In total, 217 patients were enrolled in this study. In patients with Crohn disease (CD), moderate or severe abdominal pain; prior use of methotrexate (MTX), iron, thiopurines, or biologics; history of IBD-related surgery; and stool frequency were independently associated with the prescription of probiotics. In patients with ulcerative colitis (UC), moderate or severe abdominal pain, hematochezia, stool frequency, and moderate or severe physician global assessment score were independently associated with the prescription of probiotics. CONCLUSION Increased disease activity may be associated with fewer prescriptions of probiotics in patients with IBD. However, physicians prescribed probiotics to control symptoms, such as abdominal pain and increased stool frequency in patients with UC and CD, and hematochezia in patients with UC. Additionally, the use of MTX and iron, and a history of IBD-related surgeries were associated with more frequent probiotic prescriptions in patients with CD.
Collapse
Affiliation(s)
- Joo Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| |
Collapse
|
42
|
de Freitas PNN, Silva CR, Constantin PP, Pileggi SAV, Vicari MR, Pileggi M. Fixing the Damage: The Evolution of Probiotics from Fermented Food to Biotherapeutic Products. A SUSTAINABLE GREEN FUTURE 2023:245-276. [DOI: 10.1007/978-3-031-24942-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
|
43
|
Lactobacillus gasseri JM1 Isolated from Infant Feces Alleviates Colitis in Mice via Protecting the Intestinal Barrier. Nutrients 2022; 15:nu15010139. [PMID: 36615796 PMCID: PMC9823819 DOI: 10.3390/nu15010139] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/22/2022] [Accepted: 12/24/2022] [Indexed: 12/29/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease, and the intestinal barrier is an important line of defense against intestinal disease. Herein, we investigated the effect of Lactobacillus gasseri JM1 at different doses (1 × 106, 1 × 107, 1 × 108 CFU/day) on colitis mice and explored the possible mechanism. The results showed that L. gasseri JM1 alleviated DSS-induced colitis in mice, with reductions in disease activity index (DAI), histological scores and myeloperoxidase activity as well as alleviation of colonic shortening. Furthermore, L. gasseri JM1 regulated the levels of inflammatory cytokines TNF-α, IL-6, IL-1β, and IL-10; restored the expression of Claudin-3, Occludin, ZO-1, and MUC2; and increased the number of goblet cells and acidic mucin. The 16S rDNA sequencing results indicated that intervention with L. gasseri JM1 balanced the gut microbiota structure by elevating the abundance of beneficial bacteria (Oscillospira, Clostridium and Ruminococcus) and decreasing that of harmful bacteria (Shigella and Turicibacter). Meanwhile, the contents of short-chain fatty acids (SCFAs) increased. In conclusion, L. gasseri JM1 could alleviate intestinal barrier damage in colitis mice by modulating the tight junction structures, intestinal mucus layer, inflammatory cytokines, gut microbiota, and SCFAs. It can be considered a potential preventive strategy to alleviate colitis injury.
Collapse
|
44
|
Berryman MA, Milletich PL, Petrone JR, Roesch LF, Ilonen J, Triplett EW, Ludvigsson J. Autoimmune-associated genetics impact probiotic colonization of the infant gut. J Autoimmun 2022; 133:102943. [PMID: 36356550 DOI: 10.1016/j.jaut.2022.102943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 10/16/2022] [Accepted: 10/23/2022] [Indexed: 11/09/2022]
Abstract
To exemplify autoimmune-associated genetic influence on the colonization of bacteria frequently used in probiotics, microbial composition of stool from 1326 one-year-old infants was analyzed in a prospective general-population cohort, All Babies In Southeast Sweden (ABIS). We show that an individual's HLA haplotype composition has a significant impact on which common Bifidobacterium strains thrive in colonizing the gut. The effect HLA has on the gut microbiome can be more clearly observed when considered in terms of allelic dosage. HLA DR1-DQ5 showed the most significant and most prominent effect on increased Bifidobacterium relative abundance. Therefore, HLA DR1-DQ5 is proposed to act as a protective haplotype in many individuals. Protection-associated HLA haplotypes are more likely to influence the promotion of specific bifidobacteria. In addition, strain-level differences are correlated with colonization proficiency in the gut depending on HLA haplotype makeup. These results demonstrate that HLA genetics should be considered when designing effective probiotics, particularly for those at high genetic risk for autoimmune diseases.
Collapse
Affiliation(s)
- Meghan A Berryman
- Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
| | - Patricia L Milletich
- Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
| | - Joseph R Petrone
- Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
| | - Luiz Fw Roesch
- Roesch Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA
| | - Jorma Ilonen
- Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland
| | - Eric W Triplett
- Triplett Laboratory, Institute of Food and Agriculture, Department of Microbiology and Cell Science, University of Florida, Gainesville, FL, USA.
| | - Johnny Ludvigsson
- Crown Princess Victoria's Children's Hospital and Division of Pediatrics, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| |
Collapse
|
45
|
Dargenio VN, Castellaneta S, Panico S, Papagni ME, Dargenio C, Schettini F, Francavilla R, Cristofori F. Probiotics and gastrointestinal diseases. Minerva Pediatr (Torino) 2022; 74:703-723. [PMID: 36315413 DOI: 10.23736/s2724-5276.22.07031-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
During the past decades, scientists have discovered the intimate role of the gut microbiome in human health, and since then, several papers have been published to investigate if the use of biotics (probiotics, prebiotics, synbiotics, and postbiotics) may have a beneficial impact on human health both in treatment and prevention. We now ask ourselves whether we have reached the finish line or just a new starting point, as the evidence supporting the use of biotics in several conditions still needs a lot of work. Many questions remain unanswered today because the evidence differs depending on the indication, used strain, and amount and duration of administration. Herein we will summarize the evidence on probiotics in some gastrointestinal diseases such as infantile colic, functional abdominal pain disorders, celiac disease, acute gastroenteritis, inflammatory bowel disease, and Helicobacter pylori infection.
Collapse
Affiliation(s)
- Vanessa N Dargenio
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy
| | - Stefania Castellaneta
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy
| | - Serena Panico
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy
| | - Maria E Papagni
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy
| | - Costantino Dargenio
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy
| | - Federico Schettini
- Neonatology and Neonatal Intensive Care Unit, University of Bari Aldo Moro, Bari, Italy
| | - Ruggiero Francavilla
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy -
| | - Fernanda Cristofori
- Section of Pediatrics, Interdisciplinary Department of Medicine, Giovanni XXIII Children's Hospital, University of Bari Aldo Moro, Bari, Italy
| |
Collapse
|
46
|
Sun Z, Jiang X, Wang B, Tian F, Zhang H, Yu L. Novel Phocaeicola Strain Ameliorates Dextran Sulfate Sodium-induced Colitis in Mice. Curr Microbiol 2022; 79:393. [DOI: 10.1007/s00284-022-03054-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 09/21/2022] [Indexed: 11/06/2022]
|
47
|
Li L, Liu T, Gu Y, Wang X, Xie R, Sun Y, Wang B, Cao H. Regulation of gut microbiota-bile acids axis by probiotics in inflammatory bowel disease. Front Immunol 2022; 13:974305. [PMID: 36211363 PMCID: PMC9539765 DOI: 10.3389/fimmu.2022.974305] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/31/2022] [Indexed: 12/02/2022] Open
Abstract
Inflammatory bowel disease (IBD) is characterized by chronic and relapsing inflammation of gastrointestinal tract, with steadily increased incidence and prevalence worldwide. Although the precise pathogenesis remains unclear, gut microbiota, bile acids (BAs), and aberrant immune response play essential roles in the development of IBD. Lately, gut dysbiosis including certain decreased beneficial bacteria and increased pathogens and aberrant BAs metabolism have been reported in IBD. The bacteria inhabited in human gut have critical functions in BA biotransformation. Patients with active IBD have elevated primary and conjugated BAs and decreased secondary BAs, accompanied by the impaired transformation activities (mainly deconjugation and 7α-dehydroxylation) of gut microbiota. Probiotics have exhibited certain positive effects by different mechanisms in the therapy of IBD. This review discussed the effectiveness of probiotics in certain clinical and animal model studies that might involve in gut microbiota-BAs axis. More importantly, the possible mechanisms of probiotics on regulating gut microbiota-BAs axis in IBD were elucidated, which we focused on the elevated gut bacteria containing bile salt hydrolase or BA-inducible enzymes at genus/species level that might participate in the BA biotransformation. Furthermore, beneficial effects exerted by activation of BA-activated receptors on intestinal immunity were also summarized, which might partially explain the protect effects and mechanisms of probiotics on IBD. Therefore, this review will provide new insights into a better understanding of probiotics in the therapy targeting gut microbiota-BAs axis of IBD.
Collapse
|
48
|
Peng K, Xia S, Xiao S, Yu Q. Short-chain fatty acids affect the development of inflammatory bowel disease through intestinal barrier, immunology, and microbiota: A promising therapy? J Gastroenterol Hepatol 2022; 37:1710-1718. [PMID: 35906780 DOI: 10.1111/jgh.15970] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Revised: 07/18/2022] [Accepted: 07/27/2022] [Indexed: 12/09/2022]
Abstract
Intestinal metabolites are attracting increasing interest, especially more and more studies have found they are closely related to diseases. Microbial fermentation of indigestible dietary fibers in the gut produces short chain fatty acids (SCFAs) as the main product. SCFAs can exert influences on the integrity of the intestinal epithelial and mucosal barrier, immune reactions, and the diversity of microbiota in humans. Thus, alteration in SCFAs may affect inflammatory bowel disease (IBD). In IBD, SCFAs are involved in the main pathogenic process and play an important role in the development of intestinal inflammation. Although many studies have proved that pretreatment with SCFAs can effectively ameliorate inflammation in the gut, the mechanisms are not fully understood. In this review, we describe the relationship between SCFAs and IBD from the aspects of defense barrier, immune effects, and microbial alterations. We also summarize the effects of SCFAs on comorbidities in IBD via the gut-brain, gut-liver, and gut-lung axis, and we give an overview of the prospects of their clinical application. A better understanding of the relevance of SCFAs in IBD may reveal novel targets for future study.
Collapse
Affiliation(s)
- Kaixin Peng
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Suhong Xia
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Siqi Xiao
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qin Yu
- Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.,Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
49
|
Lyu X, Chen J, Gao X, Yang J. Emerging story of gut dysbiosis in spondyloarthropathy: From gastrointestinal inflammation to spondyloarthritis. Front Cell Infect Microbiol 2022; 12:973563. [PMID: 36072223 PMCID: PMC9441705 DOI: 10.3389/fcimb.2022.973563] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 08/08/2022] [Indexed: 11/13/2022] Open
Abstract
As a set of inflammatory disorders, spondyloarthritis (SpA) exhibits distinct pathophysiological, clinical, radiological, and genetic characteristics. Due to the extra-articular features of this disorder, early recognition is crucial to limiting disability and improving outcomes. Gut dysbiosis has been linked to SpA development as evidence grows. A pathogenic SpA process is likely to occur when a mucosal immune system interacts with abnormal local microbiota, with subsequent joint involvement. It is largely unknown, however, how microbiota alterations predate the onset of SpA within the “gut-joint axis”. New microbiome therapies, such as probiotics, are used as an adjuvant therapy in the treatment of SpA, suggesting that the modulation of intestinal microbiota and/or intestinal barrier function may contribute to the prevention of SpA. In this review, we highlight the mechanisms of SpA by which the gut microbiota impacts gut inflammation and triggers the activation of immune responses. Additionally, we analyze the regulatory role of therapeutic SpA medication in the gut microbiota and the potential application of probiotics as adjunctive therapy for SpA.
Collapse
Affiliation(s)
- Xing Lyu
- Department of Rheumatology and Immunology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jieli Chen
- Discipline Construction Office, Tianjin Medical University, Tianjin, China
| | - Xingjie Gao
- Department of Biochemistry and Molecular Biology, Department of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Science, Tianjin Medical University, Tianjin, China
| | - Jie Yang
- Department of Biochemistry and Molecular Biology, Department of Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Science, Tianjin Medical University, Tianjin, China
- *Correspondence: Jie Yang,
| |
Collapse
|
50
|
di Vito R, Conte C, Traina G. A Multi-Strain Probiotic Formulation Improves Intestinal Barrier Function by the Modulation of Tight and Adherent Junction Proteins. Cells 2022; 11:cells11162617. [PMID: 36010692 PMCID: PMC9406415 DOI: 10.3390/cells11162617] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Revised: 08/16/2022] [Accepted: 08/19/2022] [Indexed: 11/25/2022] Open
Abstract
In healthy individuals, tight junction proteins (TJPs) maintain the integrity of the intestinal barrier. Dysbiosis and increased intestinal permeability are observed in several diseases, such as inflammatory bowel disease. Many studies highlight the role of probiotics in preventing intestinal barrier dysfunction. The present study aims to investigate the effects of a commercially available probiotic formulation of L. rhamnosus LR 32, B. lactis BL 04, and B. longum BB 536 (Serobioma, Bromatech s.r.l., Milan, Italy) on TJPs and the integrity of the intestinal epithelial barrier, and the ability of this formulation to prevent lipopolysaccharide-induced, inflammation-associated damage. An in vitro model of the intestinal barrier was developed using a Caco-2 cell monolayer. The mRNA expression levels of the TJ genes were analyzed using real-time PCR. Changes in the amounts of proteins were assessed with Western blotting. The effect of Serobioma on the intestinal epithelial barrier function was assessed using transepithelial electrical resistance (TEER) measurements. The probiotic formulation tested in this study modulates the expression of TJPs and prevents inflammatory damage. Our findings provide new insights into the mechanisms by which probiotics are able to prevent damage to the gut epithelial barrier.
Collapse
|