Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, have become increasingly prevalent across all human generations. Despite advances in diagnosis, effective long-term therapeutic options remain limited, with many patients experiencing recurrent symptoms after treatment. The multifactorial origins of ulcerative colitis are widely recognized, but the intestinal microbiome, particularly bacteria from the Desulfovibrionaceae family, is thought to play a central role in the pathogenesis of the disease. These bacteria contribute significantly to gut microbial functions, yet their cytotoxic and viability characteristics under disease conditions remain poorly understood. Our review provides insights on recent advancements in methodologies for assessing the cytotoxicity and viability of anaerobic intestinal bacteria, with a specific focus on their relevance to gut health and disease. We introduce overview from current literature on modern techniques including flow cytometry, high-throughput screening, and molecular-based assays, highlighting their applications in understanding the role of Desulfovibrionaceae and other gut microbes in IBD pathogenesis. By bridging methodological advancements with functional implications, this review aims to enhance our understanding of gut microbiota-host interactions, which are crucial for maintaining health and preventing disease through immune modulation, where microbiota help regulate immune responses and prevent excessive inflammation; nutrient metabolism, including the breakdown of dietary fibers into short-chain fatty acids that support gut health; and colonization resistance, where beneficial microbes outcompete harmful pathogens to maintain microbial balance.

The intestinal mucosa of ulcerative colitis patients expresses high levels of interleukin 34, and mice lacking IL-34 have more severe DSS-induced experimental colitis. There are no studies on the effects of directly upregulating intestinal IL-34 on experimental colitis in mice.

The bacteria EcN/CSF-1 and EcN/IL-34, which express CSF-1 and IL-34, respectively, were genetically engineered from Escherichia coli Nissle 1917 (EcN). Colitis mice received daily gavage of sterile PBS buffer, empty plasmid E. coli (EcN/WT), EcN/CSF-1, or EcN/IL-34. Each group of mice was assessed for body mass, clinical signs, DAI, intestinal mucosal permeability, pathological, and immunohistological changes. In vitro, NCM460 cells were treated with CSF-1 or IL-34 recombinant proteins in the presence of signaling pathway inhibitors to evaluate tight junction protein expression. Additionally, intestinal mucosal epithelial cells isolated from active UC patients were analyzed for IL-34 and tight junction protein levels.

DSS-induced colitis mice are protected by EcN/IL-34 gavage. Pathological results showed that EcN/IL-34 group colonic histological injury was significantly improved and tight junction protein ZO-1 and Occludin expression increased. In NCM460 cells, IL-34 also increased tight junction protein expression. More importantly, expression of IL-34 was positively correlated with the level of tight junction protein expression in epithelial cells of UC patients.

EcN/IL-34 can directly act on damaged intestinal mucosa, up-regulate IL-34 expression, and promote tight junction protein expression in intestinal mucosal epithelial cells to alleviate experimental colitis in mice. IL-34 may be a potential therapeutic target for ulcerative colitis, and genetically engineered bacteria carrying the cytokine may offer new ideas for treating UC.

Inflammatory bowel disease (IBD) has become a global public health problem with complex pathogenesis and limited therapeutic options. We aimed to investigate the potential mechanisms by which Bifidobacterium lactis V9 (V9) alleviated colitis in a dextran sodium sulfate-induced colitis model mice.

Mice were induced to develop colitis by drinking DSS solution to induce colitis. The expression of the relevant factors in the blood supernatant of the mice was determined by ELISA. RT-qPCR and Western blotting were used to detect mRNA and protein expression of target genes. The fecal microbiota was analyzed by 16S rRNA sequencing. Intestinal metabolites were analyzed by untargeted metabolomics.

V9 effectively improved the overall symptoms of the colitis model mice. H&E showed that V9 re-stored the intestinal tissue structure. ELISA showed that V9 decreased the levels of IL-6, IL-22, and TNF-α and increased IL-10, SP, VIP, and 5-HT. V9 increased the expression of AHR, CYP1A1, MUC2, Claudin-3, Occludin, and ZO-1, and decreased 5-hydroxytryptamine transporter and Claudin-2. V9 increased the abundance of gut microbiota in colitis mice to promote the growth of beneficial bacteria. V9 increased tryptophan metabolites, and short-chain fatty acids, and improved gut inflammation.

V9 attenuates intestinal inflammation, improves the mucosal barrier, modulates intestinal microecology and exerts a protective effect in a mouse model of DSS-induced colitis.

Consumption of probiotic products continues to increase, perhaps driven by an interest in gut health. However, the field is filled with controversy, inconsistencies, misuse of terminology, and poor communication. While the probiotic concept is biologically plausible and in some cases mechanistically well established, extrapolation of preclinical results to humans has seldom been proven in well-conducted clinical trials. With noteworthy exceptions, clinical guidance has often been derived not from large, adequately powered clinical trials but rather from comparisons of disparate, small studies with insufficient power to identify the optimal strain. The separation of probiotics from live biotherapeutic products has brought some clarity from a regulatory perspective, but in both cases, consumers should expect scientific rigor and strong supporting evidence for health claims.

The objective of this study was to investigate the effect of the Lactobacillus plantarum (L. plantarum) SS18-50 (an isolate with favorable probiotic properties following space traveling) on dextran sulfate sodium (DSS)-induced colitis in mice. Male ICR mice were randomly assigned to one of six groups: a control group, a model group, and four intervention groups comprising the isolate (SS18-50-L and SS18-50-H) and the wild type (GS18-L and GS18-H) strains. The model group and the intervention groups were administered a 3.5% DSS (w/v) solution to induce acute enteritis. The four intervention groups were administered the corresponding bacterial suspensions, SS18-50-L (1.0 × 107 CFU/mL), SS18-50-H (1.0 × 109 CFU/mL), GS18-L (1.0 × 107 CFU/mL), and GS18-H (1.0 × 109 CFU/mL). The results demonstrated that the disease activity index (DAI) score of the SS18-50-H was markedly lower than that of the CON. Subsequently, the colon tissue of mice was analyzed to determine the levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The results demonstrated that all strains within the intervention groups exhibited good performance to prevent colitis. Particularly, the SS18-50-H strain exhibited a pronounced stimulative effect on GSH, an increase in SOD activity, and a decrease in MPO activity and MDA content. The SS18-50-H treatment resulted in a notable elevation in serum somatostatin (SS) levels and a concomitant reduction in endothelin (ET) and substance P (SP) levels, which approached normal ranges. The results of the RT-qPCR analysis demonstrated that the mRNA expression levels of tumor necrosis factor (TNF-α), cyclooxygenase (COX-2), interleukin (IL-10), and interleukin (IL-6) in the SS18-50-H were significantly reduced to levels comparable to those observed in the CON. In conclusion, L. plantarum SS18-50 has been demonstrated to inhibit the development of colitis in a dose-dependent manner, thereby establishing it as a high-quality lactic acid bacterium with a colitis inhibitory effect.

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).

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.

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.

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.

The interaction between gut microbiota and the host immune system is a complex and understudied field, with cytokines like TNFα, IL-6, IL-8, and IL-10 playing pivotal roles. Commensal bacteria, including lactobacilli, respond to these cytokines through adaptive mechanisms that support their survival and function within the gut. While the influence of cytokines on pathogenic bacteria is well documented, their impact on commensal bacteria, particularly lactobacilli, remains underexplored. This study investigates the transcriptional responses of Lacticaseibacillus rhamnosus strains K32 and R19-3 to various cytokines using next-generation RNA sequencing (RNA-seq). Our findings reveal that cytokines, especially IL-8 and IL-10, significantly alter the L. rhamnosus transcriptome, affecting genes involved in carbohydrate metabolism, stress response, and transcriptional regulation. Notably, IL-8 and IL-10 induce a significant downregulation of genes related to the phosphotransferase system, suggesting a reduction in metabolic activity in response to inflammatory signals. This study unveils a previously unexplored aspect of L. rhamnosus adaptation, highlighting its intricate response to cytokine signals. By modulating gene expression, L. rhamnosus may mitigate the adverse effects of inflammation and promote gut health. These insights could inform the development of targeted probiotic therapies for inflammatory bowel disease (IBD) and other conditions with altered cytokine levels. Our results suggest that co-evolution between a host and gut microbiota enables bacteria to respond to specific cytokines through gene expression changes, revealing a unique and underexplored facet of the interaction between commensal bacteria and the host organism.

Treatments targeting the gut-brain axis (GBA) are effective at reducing symptom burden in irritable bowel syndrome (IBS). The prevalence of common mental disorders and IBS-type symptom reporting is significantly higher in inflammatory bowel disease (IBD) than would be expected, suggesting potential GBA effects in this setting. Manipulation of the GBA may offer novel treatment strategies in selected patients with IBD. We present a narrative review of the bi-directional effects of the GBA in IBD and explore the potential for GBA-targeted therapies in this setting.

We searched MEDLINE, EMBASE, EMBASE Classic, PsychINFO, and the Cochrane Central Register of Controlled Trials for relevant articles published by March 2024.

The bi-directional relationship between psychological well-being and adverse longitudinal disease activity outcomes, and the high prevalence of IBS-type symptom reporting highlight the presence of GBA-mediated effects in IBD. Treatments targeting gut-brain interactions including brain-gut behavioural treatments, neuromodulators, and dietary interventions appear to be useful adjunctive treatments in a subset of patients.

Psychological morbidity is prevalent in patients with IBD. The relationship between longitudinal disease activity outcomes, IBS-type symptom reporting, and poor psychological health is mediated via the GBA. Proactive management of psychological health should be integrated into routine care. Further clinical trials of GBA-targeted therapies, conducted in selected groups of patients with co-existent common mental disorders, or those who report IBS-type symptoms, are required to inform effective integrated models of care in the future.

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).

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.

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.

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.

Complementary and alternative medicines (CAMs) are frequently discussed by people with Inflammatory Bowel Disease (IBD). The aim of this study is to explore CAM use in Australians with IBD. This cross-sectional study was conducted via an anonymous online survey, predominantly distributed through IBD-specific social media accounts. Data collection occurred over a three-month period in 2021. Descriptive statistics, Chi-Square tests, and binary logistic regression were used to analyse quantitative data. A simple thematic analysis was conducted for qualitative free-text responses. Of the 123 responses, acupuncture (12.2%) and chiropractors (8.9%) were common CAM practitioners accessed. CAM practitioners were perceived to be 'very helpful' compared to mainstream health practitioners. The most common CAM products reported were vitamins (51.2%), probiotics (43.9%), and herbal medicine (30.9%). Common reasons for use were improved perceived improvements to wellbeing or for long-term management of IBD. Females were more likely to access CAM practitioners (OR 12.6, 95% CI 1.62-98.1, p = 0.02). Doctors were the participants' primary source of information (64.2%), although many expressed dissatisfaction with conventional therapy and the desire for a more holistic approach to care. The use of CAMs in this sample was high. Limited research into the efficacy and safety of these therapies may prevent health professionals from discussing their use with patients. Improved communication with health professionals will allow patients to be active partners in their healthcare plans and can heighten patient satisfaction with conventional therapy.

We aim to report the latest pooled analyses to evaluate the additive efficacy and safety of probiotics in the treatment of ulcerative colitis (UC).

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.

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).

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.

The human gut microbiome is well-recognized as a key player in maintaining health. However, it is a dynamic entity that changes across the lifespan. How the microbial changes that occur in later decades of life shape host health or impact age-associated inflammatory neurological diseases such as multiple sclerosis (MS) is still unclear. Current understanding of the aging gut microbiome is largely limited to cross-sectional observational studies. Moreover, studies in humans are limited by confounding host-intrinsic and extrinsic factors that are not easily disentangled from aging. This review provides a comprehensive summary of existing literature on the aging gut microbiome and its known relationships with neurological diseases, with a specific focus on MS. We will also discuss preclinical animal models and human studies that shed light on the complex microbiota-host interactions that have the potential to influence disease pathology and progression in aging individuals. Lastly, we propose potential avenues of investigation to deconvolute features of an aging microbiota that contribute to disease, or alternatively promote health in advanced age.

Inflammatory bowel disease (IBD) comprises chronic and relapsing disorders of the gastrointestinal tract, characterized by dysregulated immune responses to the gut microbiome. The gut microbiome and diet are key environmental factors that influence the onset and progression of IBD and can be leveraged for treatment. In this review, we summarize the current evidence on the role of the gut microbiome and diet in IBD pathogenesis, and the potential of microbiome-directed therapies and dietary interventions to improve IBD outcomes. We discuss available data and the advantages and drawbacks of the different approaches to manipulate the gut microbiome, such as fecal microbiota transplantation, next-generation and conventional probiotics, and postbiotics. We also review the use of diet as a therapeutic tool in IBD, including the effects in induction and maintenance, special diets, and exclusive enteral nutrition. Finally, we highlight the challenges and opportunities for the translation of diet and microbiome interventions into clinical practice, such as the need for personalization, manufacturing and regulatory hurdles, and the specificity to take into account for clinical trial design.

The gut microbiome is of paramount importance in preserving internal balance in the gastrointestinal tract; therefore, disruptions in its regulation have been linked to the development of inflammatory bowel disease (IBD). This article explores the intricate details of the gastrointestinal microbiome as it pertains to inflammatory bowel disease (IBD), with an emphasis on the Middle East. The study reviews the typical gut microbiome, modifications in inflammatory bowel disease (IBD), determinants impacting the gut microbiome of the Middle East, and prospective therapeutic interventions.

Applications for plastic polymers can be found all around the world, often discarded without any prior care, exacerbating the environmental issue. When large waste materials are released into the environment, they undergo physical, biological, and photo-degradation processes that break them down into smaller polymer fragments known as microplastics (MPs). The time it takes for residual plastic to degrade depends on the type of polymer and environmental factors, with some taking as long as 600 years or more. Due to their small size, microplastics can contaminate food and enter the human body through food chains and webs, causing gastrointestinal (GI) tract pain that can range from local to systemic. Microplastics can also acquire hydrophobic organic pollutants and heavy metals on their surface, due to their large surface area and surface hydrophobicity. The levels of contamination on the microplastic surface are significantly higher than in the natural environment. The gut-brain axis (GB axis), through which organisms interact with their environment, regulate nutritional digestion and absorption, intestinal motility and secretion, complex polysaccharide breakdown, and maintain intestinal integrity, can be altered by microplastics acting alone or in combination with pollutants. Probiotics have shown significant therapeutic potential in managing various illnesses mediated by the gut-brain axis. They connect hormonal and biochemical pathways to promote gut and brain health, making them a promising therapy option for a variety of GB axis-mediated illnesses. Additionally, taking probiotics with or without food can reduce the production of pro-inflammatory cytokines, reactive oxygen species (ROS), neuro-inflammation, neurodegeneration, protein folding, and both motor and non-motor symptoms in individuals with Parkinson's disease. This study provides new insight into microplastic-induced gut dysbiosis, its associated health risks, and the benefits of using both traditional and next-generation probiotics to maintain gut homeostasis.

There is increasing evidence that probiotic and commensal bacteria play a role in substrate metabolism, energy harvesting and intestinal homeostasis, and may exert immunomodulatory activities on human health. In addition, recent research suggests that these microorganisms interact with vitamins and minerals, promoting intestinal and metabolic well-being while producing vital microbial metabolites such as short-chain fatty acids (SCFAs). In this regard, there is a flourishing field exploring the intricate dynamics between vitamins, minerals, SCFAs, and commensal/probiotic interactions. In this review, we summarize some of the major hypotheses beyond the mechanisms by which commensals/probiotics impact gut health and their additional effects on the absorption and metabolism of vitamins, minerals, and SCFAs. Our analysis includes comprehensive review of existing evidence from preclinical and clinical studies, with particular focus on the potential interaction between commensals/probiotics and micronutrients. Finally, we highlight knowledge gaps and outline directions for future research in this evolving field.

As resistance to conventional antibiotics among bacteria continues to increase, researchers are increasingly focusing on alternative strategies for preventing and treating bacterial infections, one of which is microbiota modulation. The objective of this review is to analyze the scientific literature on the immunomodulatory effects of probiotics in bacterial infections. This is an integrative review of the literature based on systematic steps, with searches performed in the databases Medline, PubMed, Scopus, Embase, and ScienceDirect. The most prevalent bacterial genera used to evaluate infectious processes were Salmonella, Escherichia, Klebsiella, and Streptococcus. Lactobacillus was the most commonly used probiotic genus, with Lactobacillus delbrueckii subsp. bulgaricus is the most frequently used species. In most studies, prophylactic treatment with concentrations of probiotics equal to or greater than 8 log CFU/mL was chosen. However, there was considerable heterogeneity in terms of effective treatment duration, indicating that the results cannot be generalized across all studies. This review found that probiotics interact with the immune system through different mechanisms and have a positive effect on preventing different types of bacterial infections.

Probiotics are living microorganisms that provide health benefits to their hosts, potentially aiding in the treatment or prevention of various diseases, including diarrhea, irritable bowel syndrome, ulcerative colitis, and Crohn's disease. Motivated by successful applications of link prediction in medical and biological networks, we applied link prediction to the probiotic-disease network to identify unreported relations. Using data from the Probio database and International Classification of Diseases-10th Revision (ICD-10) resources, we constructed a bipartite graph focused on the relationship between probiotics and diseases. We applied customized link prediction algorithms for this bipartite network, including common neighbors, Jaccard coefficient, and Adamic/Adar ranking formulas. We evaluated the results using Area under the Curve (AUC) and precision metrics. Our analysis revealed that common neighbors outperformed the other methods, with an AUC of 0.96 and precision of 0.6, indicating that basic formulas can predict at least six out of ten probable relations correctly. To support our findings, we conducted an exact search of the top 20 predictions and found six confirming papers on Google Scholar and Science Direct. Evidence suggests that Lactobacillus jensenii may provide prophylactic and therapeutic benefits for gastrointestinal diseases and that Lactobacillus acidophilus may have potential activity against urologic and female genital illnesses. Further investigation of other predictions through additional preclinical and clinical studies is recommended. Future research may focus on deploying more powerful link prediction algorithms to achieve better and more accurate results.

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.

To sustain host health and provide the microbial community with a nutrient-rich environment, the host and gut microbiota must interact with one another. These interactions between commensal bacterial and intestinal epithelial cells (IECs) serve as the first line of defense against gut microbiota in preserving intestinal homeostasis. In this microenvironment, the post-biotics and similar molecules such as p40 exert several beneficial effects through regulation of IECs. Importantly, post-biotics were discovered to be transactivators of the EGF receptor (EGFR) in IECs, inducing protective cellular responses and alleviating colitis. The transient exposure to post-biotics such as p40 during the neonatal period reprograms IECs by upregulation of a methyltransferase, Setd1β, leading to a sustained increase in TGF- β release for the expansion of regulatory T cells (Tregs) in the intestinal lamina propria and durable protection against colitis in adulthood. This crosstalk between the IECs and post-biotic secreted factors was not reviewed previously. Therefore, this review describes the role of probiotic-derived factors in the sustainability of intestinal health and improving gut homeostasis via certain signaling pathways. In the era of precision medicine and targeted therapies, more basic, preclinical, and clinical evidence is needed to clarify the efficacy of probiotics released as functional factors in maintaining intestinal health and preventing and treating disease.

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".

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.

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.

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.

Metabolic exchanges between strains in gut microbial communities shape their composition and interactions with the host. This study investigates the metabolic synergy between potential probiotic bacteria and Saccharomyces boulardii, aiming to enhance anti-inflammatory effects within a multi-species probiotic community. By screening a collection of 85 potential probiotic bacterial strains, we identified two strains that demonstrated a synergistic relationship with S. boulardii in pairwise co-cultivation. Furthermore, we computationally predicted cooperative communities with symbiotic relationships between S. boulardii and these bacteria. Experimental validation of 28 communities highlighted the role of S. boulardii as a key player in microbial communities, significantly boosting the community's cell number and production of anti-inflammatory effectors, thereby affirming its essential role in improving symbiotic dynamics. Based on our observation, one defined community significantly activated the aryl hydrocarbon receptor-a key regulator of immune response-280-fold more effectively than the community without S. boulardii. This study underscores the potential of microbial communities for the design of more effective probiotic formulations.

Artificial intelligence is increasingly entering everyday healthcare. Large language model (LLM) systems such as Chat Generative Pre-trained Transformer (ChatGPT) have become potentially accessible to everyone, including patients with inflammatory bowel diseases (IBD). However, significant ethical issues and pitfalls exist in innovative LLM tools. The hype generated by such systems may lead to unweighted patient trust in these systems. Therefore, it is necessary to understand whether LLMs (trendy ones, such as ChatGPT) can produce plausible medical information (MI) for patients. This review examined ChatGPT's potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists. From the review of the outputs provided by ChatGPT, this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases. Further studies and refinement of the ChatGPT, possibly aligning the outputs with the leading medical evidence provided by reliable databases, are needed.

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.

Ulcerative colitis (UC) clinical guidelines include the best available evidence, although not all clinical situations are answered, so their management can be controversial. The aim of this study is to identify the situations of mild to moderate UC susceptible to controversy and to evaluate the degree of agreement or disagreement with specific proposals.

Inflammatory bowel disease (IBD) expert discussion meetings were used to identify criteria, attitudes and opinions regarding the management of UC. A Delphi questionnaire was then developed with 60 items regarding antibiotics, salicylates and probiotics; local, systemic and topical corticosteroids; and immunosuppressants.

Consensus was reached in 44 statements (73.3%); 32 in agreement (53.3%) and 12 in disagreement (20.0%). Some of them were: it is not necessary the systematic use of antibiotics despite the severity of the outbreak, being reserved when there is suspicion of infection or systemic toxicity; when faced with a mild-moderate outbreak of UC and in patients who do not respond to aminosalicylates, it is appropriate to use a dose of beclomethasone of 10mg/day for one month and 5mg/day for another month; it is advised that the dose of azathioprine be administered in a single dose.

IBD experts agree on most of the proposals identified for managing mild to moderate UC and there is a need for scientific evidence in some specific situations where expert opinion may be helpful.

Genetically engineered bacteria (GEB) have shown significant promise to revolutionize modern medicine. These engineered bacteria with unique properties such as enhanced targeting, versatility, biofilm disruption, reduced drug resistance, self-amplification capabilities, and biodegradability represent a highly promising approach for targeted drug delivery and cancer theranostics. This innovative approach involves modifying bacterial strains to function as drug carriers, capable of delivering therapeutic agents directly to specific cells or tissues. Unlike synthetic drug delivery systems, GEB are inherently biodegradable and can be naturally eliminated from the body, reducing potential long-term side effects or complications associated with residual foreign constituents. However, several pivotal challenges such as safety and controllability need to be addressed. Researchers have explored novel tactics to improve their capabilities and overcome existing challenges, including synthetic biology tools (e.g., clustered regularly interspaced short palindromic repeats (CRISPR) and bioinformatics-driven design), microbiome engineering, combination therapies, immune system interaction, and biocontainment strategies. Because of the remarkable advantages and tangible progress in this field, GEB may emerge as vital tools in personalized medicine, providing precise and controlled drug delivery for various diseases (especially cancer). In this context, future directions include the integration of nanotechnology with GEB, the focus on microbiota-targeted therapies, the incorporation of programmable behaviors, the enhancement in immunotherapy treatments, and the discovery of non-medical applications. In this way, careful ethical considerations and regulatory frameworks are necessary for developing GEB-based systems for targeted drug delivery. By addressing safety concerns, ensuring informed consent, promoting equitable access, understanding long-term effects, mitigating dual-use risks, and fostering public engagement, these engineered bacteria can be employed as promising delivery vehicles in bio- and nanomedicine. In this review, recent advances related to the application of GEB in targeted drug delivery and cancer therapy are discussed, covering crucial challenging issues and future perspectives.

Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.

Recent evidence demonstrates potential links between mitochondrial dysfunction and inflammatory bowel diseases (IBD). In addition, bidirectional interactions between the intestinal microbiota and host mitochondria may modulate intestinal inflammation. We observed previously that mice deficient in the mitochondrial protein MCJ (Methylation-controlled J protein) exhibit increased susceptibility to DSS colitis. However, it is unclear whether this phenotype is primarily driven by MCJ-/- associated gut microbiota dysbiosis or by direct effects of MCJ-deficiency. Here, we demonstrate that fecal microbiota transplantation (FMT) from MCJ-deficient into germ-free mice was sufficient to confer increased susceptibility to colitis. Therefore, an FMT experiment by cohousing was designed to alter MCJ-deficient microbiota. The phenotype resulting from complex I deficiency was reverted by FMT. In addition, we determined the protein expression pathways impacted by MCJ deficiency, providing insight into the pathophysiology of IBD. Further, we used magnetic activated cell sorting (MACS) and 16S rRNA gene sequencing to characterize taxa-specific coating of the intestinal microbiota with Immunoglobulin A (IgA-SEQ) in MCJ-deficient mice. We show that high IgA coating of fecal bacteria observed in MCJ-deficient mice play a potential role in disease progression. This study allowed us to identify potential microbial signatures in feces associated with complex I deficiency and disease progression. This research highlights the importance of finding microbial biomarkers, which might serve as predictors, permitting the stratification of ulcerative colitis (UC) patients into distinct clinical entities of the UC spectrum.

The consortium of microbes inhabiting the human body, together with their encoded genes and secreted metabolites, is referred to as the "human microbiome." Several studies have established a link between the composition of the microbiome and its impact on human health. This impact spans local gastrointestinal inflammation to systemic autoimmune disorders and neurodegenerative diseases such as Alzheimer's and Autism. Some of these links have been validated by rigorous experiments that identify specific strains as mediators or drivers of a particular condition. Consequently, the development of probiotics to compensate for a missing beneficial microbe(s) has advanced and become popular, especially in the treatment of irritable bowel diseases and to restore disrupted gut flora after antibiotic administration. The widespread use of probiotics is often advocated as a natural ecological therapy. However, this perception is not always accurate, as there is a potential for unexpected interactions when administering live microbial cultures. Here, we designed this research to explore the intricate interactions among probiotics, the host, and microbes through a series of experiments. Our objectives included assessing their immunomodulatory effects, response to oral medications, impact on microbial population dynamics, and mediation of antibiotic resistance. To achieve these goals, we employed diverse experimental protocols, including cell-based enzyme -linked immunosorbent assay (ELISA), antibiotic susceptibility testing, antimicrobial activity assays, computational prediction of probiotic genes responsible for antibiotic resistance, polymerase chain reaction (PCR)-based validation of predicted genes, and survival assays of probiotics in the presence of selected oral medications. Our findings highlight that more than half of the tested probiotics trigger an inflammatory response in the Caco-2 cell line, are influenced by oral medications, exhibit antibacterial activity, and possess genes encoding antimicrobial resistance. These results underscore the necessity for a reevaluation of probiotic usage and emphasize the importance of establishing regulations to govern probiotic testing, approval, and administration.

Ulcerative colitis (UC) is presently considered a multifactorial pathology, which may lead to persistent inflammatory action of the gastrointestinal tract (GIT) because of an improperly managed immunological reactivity to the intestinal microbiota found in the GIT. The immune response to common commensal microbes plays an essential role in intestinal inflammation related to UC synbiotics, and it is an important element in the optimal therapy of UC. Therefore, synbiotics, i.e., a mixture of prebiotics and probiotics, may help control the diseased state. Synbiotics alleviate the inflammation of the colon by lowering the reactive oxygen species (ROS) and improving the level of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). Prebiotic supplementation is not a common practice at the moment, despite numerous research findings proving that the benefits of both probiotics and prebiotics encourage their continued existence and positioning in the GIT, with positive effects on human health by managing the inflammatory response. However, the fact that there have been fewer studies on the treatment of UC with different probiotics coupled with selected prebiotics, i.e., synbiotics, and the outcomes of these studies have been very favorable. This evidence-based study explores the possible role of ROS, SOD, and synbiotics in managing the UC. The proposed review also focuses on the role of alteration of gut microbiota, antioxidant defense in the gastrointestinal tract, and the management of UC. Thus, the current article emphasizes oxidative stress signaling in the GI tract, oxidative stress-based pathomechanisms in UC patients, and UC therapies inhibiting oxidative stress' effects.

Probiotics are microorganisms that confer benefits to the host, and, for this reason, they have been proposed in several pathologic states. Specifically, probiotic bacteria have been investigated as a therapeutic option in ulcerative colitis (UC) patients, but clinical results are dishomogeneous. In particular, many probiotic species with different therapeutic schemes have been proposed, but no study has investigated probiotics in monotherapy in adequate trials for the induction of remission. Lactobacillus rhamnosus GG (LGG) is the more intensively studied probiotic and it has ideal characteristics for utilization in UC patients. The aim of the present study is to investigate the clinical efficacy and safety of LGG administration in an open trial, delivered in monotherapy at two different doses, in UC patients with mild-moderate disease. The UC patients with mild-moderate disease activity (Partial Mayo score ≥ 2) despite treatment with oral mesalamine were included. The patients stopped oral mesalamine and were followed up for one month, then were randomized to receive LGG supplement at dose of 1.2 or 2.4 × 10¹⁰ CFU/day for one month. At the end of the study, the clinical activity was evaluated and compared to that at the study entrance (efficacy). Adverse events were recorded (safety). The primary end-point was clinical improvement (reduction in the Partial Mayo score) and no serious adverse events, while the secondary end-points were the evaluation of different efficacies and safeties between the two doses of LGG. The patients with disease flares dropped out of the study and went back to standard therapy. The efficacy data were analyzed in an intention-to-treat (ITT) and per-protocol (PP) analysis. Out of the 76 patients included in the study, 75 started the probiotic therapy (n = 38 and 37 per group). In the ITT analysis, 32/76 (42%) responded to treatment, 21/76 (28%) remained stable, and 23/76 (30%) had a worsening of their clinical condition; 55 (72%) completed the treatment and were analyzed in a PP analysis: 32/55 (58%) had a clinical response, 21 (38%) remained stable, and 2 (4%) had a light worsening of their clinical condition (p < 0.0001). Overall, 37% of the patients had a disease remission. No severe adverse event was recorded, and only one patient stopped therapy due to obstinate constipation. No difference in the clinical efficacy and safety has been recorded between groups treated with different doses of LGG. The present prospective clinical trial demonstrates, for the first time, that LGG in monotherapy is safe and effective for the induction of remission in UC patients with mild-moderate disease activity (ClinicalTrials.gov identifier: NCT04102852).

It has been hypothesised that the regular consumption of safe, live microbes confers health-promoting attributes, including the prevention of disease. To address this hypothesis, we propose a scoping review approach that will systematically assess the large corpus of relevant literature that is now available on this research topic. This article outlines a protocol for a scoping review of published studies on interventions with live microbes in non-patient populations across eight health categories. The scoping review aims to catalogue types of interventions, measured outcomes, dosages, effectiveness, as well as current research gaps.

The scoping review will follow the six-staged protocol as proposed by Arksey and O'Malley and will include the following stages: defining the research questions (stage 1); defining the eligibility criteria and finalising search strategy (stage 2); selection of studies based on the eligibility criteria (stage 3); development of a data extraction framework and charting of data (stage 4); aggregation of results and summarisation of findings (stage 5); and the optional consultation with stakeholders (stage 6), which will not be performed.

Since the scoping review synthesises information from existing literature, no separate ethical approval is required. The findings of the scoping review will be communicated for publication to an open-access, peer-reviewed scientific journal, presented at relevant conferences, and disseminated at future workshops with all relevant data and documents being available online through the Open Science Framework (https://osf.io/kvhe7).

Inflammatory bowel disease (IBD) patients are accompanied by impaired intestinal barrier integrity and gut microbiota dysbiosis. Strategies targeting the gut microbiota are potential therapies for preventing and ameliorating IBD.

The potential roles of two probiotic stains, Bifidobacterium longum BL986 (BL986) and Lactobacillus casei LC122 (LC122), on intestinal mucosal barrier function and microbiota in IBD zebrafish of different ages were investigated.

BL986 and LC122 treatment promoted the development and increased the microbiota diversity in larval zebrafish. Both probiotic treatment ameliorated mortality, promoted intestinal mucus secretion, and reduced the expression of inflammatory markers, thereby improving intestinal mucosal barrier function in dextran sulfate sodium salt (DSS)-induced ulcerative colitis (UC) and 2,4,6-trinitro-benzenesulfonicacid (TNBS)-induced Crohn's disease (CD) models in zebrafish. Moreover, the composition and function of microbiota were altered in IBD zebrafish, and probiotics treatment displayed prominent microbiota features. BL986 was more potent in the DSS-induced UC model, and increased the abundance of Faecalibaculum and butyric acid levels. LC122 exerted better protection against TNBS-induced CD, and increased the abundance of Enhydrobacter and acetic acid levels. Furthermore, the effect of probiotics was stronger in larval and aged zebrafish.

The impact of probiotics on IBD might differ from the subtypes of IBD and the age of the zebrafish, suggesting the types of disease and age should be taken into full consideration during the practical usage of probiotics.

Bile salt hydrolases are thought to be the gatekeepers of bile acid metabolism. To study the role of BSH in colitis, we investigated the ameliorative effects of different BSH-knockout strains of Lactiplantibacillus plantarum AR113. The results showed that L. plantarum Δbsh 1 and Δbsh 3 treatments did not improve body weight and alleviate the hyperactivated myeloperoxidase activity to the DSS group. However, the findings for L. plantarum AR113, L. plantarum Δbsh 2 and Δbsh 4 treatments were completely opposite. The double and triple bsh knockout strains further confirmed that BSH 1 and BSH 3 are critical for the ameliorative effects of L. plantarum AR113. In addition, L. plantarum Δbsh 1 and Δbsh 3 did not significantly inhibit the increase in pro-inflammatory cytokines or the decrease in an anti-inflammatory cytokine. These results suggest that BSH 1 and BSH 3 in L. plantarum play important roles in alleviating enteritis symptoms.

The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty acids (SCFA) produced by commensal bacteria through fermentation of indigestible fibres are considered key regulators in orchestrating the host immune response to microbial colonization by regulating phagocytosis, chemokine and central signalling pathways of cell growth and apoptosis, thereby shaping the composition and functionality of the intestinal epithelial barrier. Although research of the last decades provided valuable insight into the pleiotropic functions of SCFAs and their capability to maintain human health, mechanistic details on how SCFAs act across different cell types and other organs are not fully understood. In this review, we provide an overview of the various functions of SCFAs in regulating cellular metabolism, emphasizing the orchestration of the immune response along the gut-brain, the gut-lung and the gut-liver axes. We discuss their potential pharmacological use in inflammatory diseases and infections and highlight new options of relevant human three-dimensional organ models to investigate and validate their biological functions in more detail.

Inflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.

Ulcerative colitis (UC) is a chronic inflammatory disease that compromises the colon, affecting the quality of life of individuals of any age. In practice, there is a wide spectrum of clinical situations. The advances made in the physio pathogenesis of UC have allowed the development of new, more effective and safer therapeutic agents.

To update and expand the evaluation of the efficacy and safety of relevant treatments for remission induction and maintenance after a mild, moderate or severe flare of UC.

Gastroenterologists, coloproctologists, general practitioners, family physicians and others health professionals, interested in the treatment of UC.

GADECCU authorities obtained authorization from GETECCU to adapt and update the GETECCU 2020 Guide for the treatment of UC. Prepared with GRADE methodology. A team was formed that included authors, a panel of experts, a nurse and a patient, methodological experts, and external reviewers. GRADE methodology was used with the new information.

A 118-page document was prepared with the 44 GADECCU 2022 recommendations, for different clinical situations and therapeutic options, according to levels of evidence. A section was added with the new molecules that are about to be available.

This guideline has been made in order to facilitate decision-making regarding the treatment of UC, adapting and updating the guide prepared by GETECCU in the year 2020.