Numerous studies have accelerated the knowledge expansion on the role of gut microbiota in inflammatory bowel disease (IBD). However, the precise mechanisms behind host-microbe cross-talk remain largely undefined, due to the complexity of the human intestinal ecosystem and multiple external factors. In this review, we introduce the interactome concept to systematically summarize how intestinal dysbiosis is involved in IBD pathogenesis in terms of microbial composition, functionality, genomic structure, transcriptional activity, and downstream proteins and metabolites. Meanwhile, this review also aims to present an updated overview of the relevant mechanisms, high-throughput multi-omics methodologies, different types of multi-omics cohort resources, and computational methods used to understand host-microbiota interactions in the context of IBD. Finally, we discuss the challenges pertaining to the integration of multi-omics data in order to reveal host-microbiota cross-talk and offer insights into relevant future research directions.

Joint inflammation is the most common extraintestinal manifestation of Crohn's disease (CD). Although alterations in the enteric microbiota are described in CD with spondyloarthritis (CD-SpA), it is not known whether distinct taxa serve as markers for clinical subtypes of axial (AxSpA) or peripheral SpA (pSpA) in CD. Moreover, it is not yet known whether these taxa generate a specific systemic IgG response. Here, we sequenced the fecal microbiome from 106 individuals (44 CD, 39 CD-SpA, 14 CD-AxSpA, and 9 healthy controls [HC]). This unique cohort revealed distinct taxonomic compositions of CD and CD-SpA compared to HC and demonstrates that the composition of the CD-AxSpA microbiome is distinct from that of CD-pSpA. Using autologous serum, we identified enteric bacteria recognized by serum IgG and demonstrate differences in the IgG coating index of specific bacterial genera associated with CD-SpA. The IgG coating index of Mediterraneibacter gnavus differentiated patients with CD-pSpA and is positively associated with joint disease activity. This work illustrates divergent microbiome compositions in CD-SpA subtypes, as well as the recognition of distinct enteric bacteria by serum IgG with the potential to serve as a marker of joint inflammation in CD.

In the gut, microRNAs (miRNAs) produced by intestinal epithelial cells are secreted into the lumen and can shape the composition and function of the gut microbiome. Crosstalk between gut microbes and the host plays a key role in irritable bowel syndrome (IBS) and inflammatory bowel diseases, yet little is known about how the miRNA-gut microbiome axis contributes to the pathogenesis of these conditions. Here, we investigate the ability of miR-21, a miRNA that we found decreased in fecal samples from IBS patients, to associate with and regulate gut microbiome function. When incubated with the human fecal microbiota, miR-21 revealed a rapid internalization or binding to microbial cells, which varied in extent across different donor samples. Fluorescence-activated cell sorting and sequencing of microbial cells incubated with fluorescently labeled miR-21 identified organisms belonging to the genera Bacteroides, Limosilactobacillus, Ruminococcus, or Coprococcus, which predominantly interacted with miR-21. Surprisingly, these and other genera also interacted with a miRNA scramble control, suggesting that physical interaction and/or uptake of these miRNAs by gut microbiota is not sequence-dependent. Nevertheless, transcriptomic analysis of the gut commensal Bacteroides thetaiotaomicron revealed a miRNA sequence-specific effect on bacterial transcript levels. Supplementation of miR-21, but not of small RNA controls, resulted in significantly altered levels of many cellular transcripts and increased transcription of a biosynthetic operon for indole and L-tryptophan, metabolites known to regulate host inflammation and colonic motility. Our study identifies a novel putative miR-21-dependent pathway of regulation of intestinal function through the gut microbiome with implications for gastrointestinal conditions.

The mammalian gut represents one of the largest and most dynamic host-microbe interfaces. Host-derived microRNAs (miRNAs), released from the gut epithelium into the lumen, have emerged as important contributors to host-microbe crosstalk. Levels of several miRNAs are altered in the stool of patients with irritable bowel syndrome or inflammatory bowel disease. Understanding how miRNAs interact with and shape gut microbiota function is crucial as it may enable the development of new targeted treatments for intestinal diseases. This study provides evidence that the miRNA miR-21 can rapidly associate with diverse microbial cells form the gut and increase levels of transcripts involved in tryptophan synthesis in a ubiquitous gut microbe. Tryptophan catabolites regulate key functions, such as gut immune response or permeability. Therefore, this mechanism represents an unexpected host-microbe interaction and suggests that host-derived miR-21 may help regulate gut function via the gut microbiota.

Lactobacillus fermentum has been shown to improve intestinal health and treat colitis; however, its precise efficacy and mechanisms in inflammatory bowel disease remain unclear.

This study aimed to evaluate whether L fermentum and its metabolites, extracellular vesicles, and other components could modulate intestinal barrier function and gut microbiota to alleviate dextran sulfate sodium (DSS)-induced colitis in mice.

Forty-eight mice were randomly assigned to 6 groups: control, DSS, L fermentum+DSS group (LF+DSS), heat-inactivated L fermentum+DSS group (LHF+DSS), L fermentum supernatant solution+DSS group (LSF+DSS), and L fermentum extracellular vesicles+DSS group (LEV+DSS). After a 1-wk acclimation, mice were gavaged daily for 3 wk. Fresh cultures, including live (LF+DSS), heat-inactivated (LHF+DSS), supernatant (LSF+DSS), and extracellular vesicles (LEV+DSS), were prepared daily. During the final 7 d, the control group received normal water, and the other groups received 3% DSS. Data were collected daily, followed by sample collection from the mice.

In this study, significant reductions (P < 0.05) in body weight changes, disease activity index, intestinal damage, and histology scores were observed in the treatment groups, especially LEV+DSS and LF+DSS. Additionally, compared with the DSS group, colonic mucus secretion, as well as claudin-1 and occludin expression, increased significantly (P < 0.05) in the LEV+DSS and LF+DSS groups, whereas proinflammatory cytokines IL-1β and TNF-α decreased (P < 0.05) and IL-10 increased (P < 0.05) in the LEV+DSS group. L fermentum and its components significantly regulated gut microbiota α-diversity and β-diversity, affecting overall composition. Linear discriminant analysis effect size analysis revealed an enrichment of beneficial bacteria including Prevotellaceae_UCG-001, Romboutsia, and Ruminococcus species in the LF+DSS group and Akkermansia, Odoribacter, and Marvinbryantia species in the LEV+DSS group. Both L fermentum and its extracellular vesicles significantly downregulated the gene expression of TNF-α and IL-1β, whereas the expression of IL-10 was upregulated, thereby contributing to the alleviation of colitis symptoms.

This study reveals that L fermentum alleviates colitis through modulation of the gut microbiota and reinforcement of the intestinal mucosal barrier, with its extracellular vesicles potentially playing a key role in this regulatory process.

Understanding the role of the gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD) has been an area of intense research over the past decades. Patients with IBD exhibit alterations in their microbial composition compared to healthy controls. However, studies focusing solely on taxonomic analyses have struggled to deliver replicable findings across cohorts regarding which microbial species drive the distinct patterns in IBD. The focus of research has therefore shifted to studying the functionality of gut microbes, especially by investigating their effector molecules involved in the immunomodulatory functions of the microbiota, namely metabolites. Metabolic profiles are altered in IBD, and several metabolites have been shown to play a causative role in shaping immune functions in animal models. Therefore, understanding the complex communication between the microbiota, metabolites, and the host bears great potential to unlock new biomarkers for diagnosis, disease course and therapy response as well as novel therapeutic options in the treatment of IBD. In this review, we primarily focus on promising classes of metabolites which are thought to exert beneficial effects and are generally decreased in IBD. Though results from human trials are promising, they have not so far provided a large-scale break-through in IBD-therapy improvement. We therefore propose tailored personalized supplementation of microbiota and metabolites based on multi-omics analysis which accounts for the individual microbial and metabolic profiles in IBD patients rather than one-size-fits-all approaches.

The benefits of regular physical activity (PA) on disease prevention and treatment outcomes have been recognized for centuries. However, only recently has interorgan communication triggered by the release of "myokines" from contracting skeletal muscles emerged as a putative mechanism by which exercise confers protection against numerous disease states. Cross-talk between active skeletal muscles and the gut microbiota reveal how regular PA boosts host immunity, facilitates a more diverse gut microbiome and functional metabolome, and plays a positive role in energy homeostasis and metabolic regulation. In contrast, and despite the large interindividual variation in the human gut microbiome, reduced microbial diversity has been implicated in several diseases of the gastrointestinal (GI) tract, systemic immune diseases, and cancers. Although prolonged, intense, weight-bearing exercise conducted in extreme conditions can increase intestinal permeability, compromising gut-barrier function and resulting in both upper and lower GI symptoms, these are transient and benign. Accordingly, the gut microbiome has become an attractive target for modulating many of the positive effects of regular PA on GI health and disease, although the precise dose of exercise required to induce favourable changes in the microbiome and enhance host immunity is currently unknown. Future efforts should concentrate on gaining a deeper understanding of the factors involved in exercise-gut interactions through the generation of functional 'omics readouts (ie, metatranscriptomics, metaproteomics, and metabolomics) that have the potential to identify functional traits of the microbiome that are linked to host health and disease states, and validating these interactions in experimental and preclinical systems. A greater understanding of how PA interacts with the GI tract and the microbiome may enable targeted therapeutic strategies to be developed for individuals and populations at risk for a variety of GI diseases.

The gastrointestinal microbiome influences physiological functions and is altered in a variety of diseases. The causality of "dysbiosis" in the pathogenesis is not always proven; association studies are often involved. Patients with IBD, bacteria, fungi, bacteriophages, and archaea show disease-typical patterns associated with metabolome disturbances. Fecal microbiome transfer (FMT) for treating various diseases is the subject of numerous clinical studies. Currently, recurrent Clostridioides difficile infection (rCDI) is the only confirmed indication recommended in medical guidelines. In Germany, the FMT is subject to the Medicines Act and may only be carried out as part of individual healing attempts or clinical studies. For patient safety, repeated donor screening, ideally with the construction of a chair bench, is necessary. This significantly limits the nationwide availability of the FMT in Germany. Microbiota-based therapeutics prepared from the stool of tested donors have recently been approved by the US Food and Drug Administration (FDA) for the prevention of rCDI. More microbiome-based medicines can be expected in the future.

Much of life on Earth is at the mercy of currents and flow. Residence time (τ) estimates how long organisms and resources remain in a system based on the ratio of volume (V) to flow rate (Q). Short τ should promote immigration but limit species establishment, while long τ should favour species that survive on limited resources. Theory suggests these opposing forces shape the abundance, diversity and function of flowing systems. We experimentally tested how residence time affects a lake microbial community by exposing chemostats to a τ gradient spanning seven orders of magnitude. Microbial abundance, richness and evenness increased non-linearly with τ, while functions like productivity and resource consumption declined. Taxa formed distinct clusters of short- and long-τ specialists consistent with niche partitioning. Our findings demonstrate that residence time drives biodiversity and community function in flowing habitats that are commonly found in environmental, engineered and host-associated ecosystems.

This editorial, inspired by a recent study published in the World Journal of Gastrointestinal Oncology, covers the research findings on microbiota changes in various diseases. In recurrent colorectal polyps, the abundances of Klebsiella, Parvimonas, and Clostridium increase, while those of Bifidobacterium and Lactobacillus decrease. This dysbiosis may promote the formation and recurrence of polyps. Similar microbial changes have also been observed in colorectal cancer, inflammatory bowel disease, autism spectrum disorder, and metabolic syndrome, indicating the role of increased pathogens and decreased probiotics in these conditions. Regulating the gut microbiota, particularly by increasing probiotic levels, may help prevent polyp recurrence and promote gut health. This microbial intervention strategy holds promise as an adjunctive treatment for patients with colorectal polyps.

The term "gut microbiota" primarily refers to the ecological community of various microorganisms in the gut, which constitutes the largest microbial community in the human body. Although adequate bowel preparation can improve the results of colonoscopy, it may interfere with the gut microbiota. Bowel preparation for colonoscopy can lead to transient changes in the gut microbiota, potentially affecting an individual's health, especially in vulnerable populations, such as patients with inflammatory bowel disease. However, measures such as oral probiotics may ameliorate these adverse effects. We focused on the bowel preparation-induced changes in the gut microbiota and host health status, hypothesized the factors influencing these changes, and attempted to identify measures that may reduce dysbiosis, thereby providing more information for individualized bowel preparation for colonoscopy in the future.

Gut microbiota dysbiosis significantly impacts ulcerative colitis (UC) progression and exacerbation. Probiotics show promise in UC management. This study evaluated the effects of different doses of Bacillus pumilus LV149, an aquatic-derived probiotic, on gut injury repair in male C57BL/6 mice with dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) and investigated the underlying mechanisms.

UC was induced by allowing mice free access to a 3% DSS solution for 7 days, with concurrent daily oral gavage of either a low (LV149-L, 1 × 108 CFU/day/mouse) or high (LV149-H, 1 × 109 CFU/day/mouse) dose of LV149. The effects were assessed through physiological parameters, intestinal barrier integrity, inflammation, gut microbiota composition, and transcriptomic changes.

LV149 significantly improved pathological symptoms, including weight loss and disease activity index (DAI), and reduced colon shortening in a dose-dependent manner and inflammatory damage. The intervention also restored gut barrier function by upregulating mucins, goblet cell counts, and tight junction proteins (ZO-1, occludin, and claudin-1) in colonic tissue, along with reducing serum lipopolysaccharide (LPS) levels. Notably, only the LV149-H significantly decreased the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, while both doses increased the expression of the anti-inflammatory cytokine IL-10 in a dose-dependent in colonic tissue. LV149 further modulated the gut microbiota, increasing beneficial bacteria and reducing pathogenic populations. Transcriptomic analysis indicated that LV149-L may exert gut repair effects via the IL-17 signaling pathway, whereas LV149-H appears to act through the JAK-STAT signaling pathway.

This study demonstrated that LV149, particularly at a higher dose, effectively mitigated DSS-induced colonic injury by modulating gut microbiota, enhancing gut barrier integrity, and reducing inflammation. The dose-dependent effects underscored LV149-H's potential as a therapeutic agent for UC due to its stronger anti-inflammatory properties and gut-protective effects.

Inflammatory bowel disease (IBD) frequently affects women of childbearing age who may consider breastfeeding. Although breastfeeding has numerous benefits, there remain concerns regarding the safety of breastfeeding among women with IBD. Breastfeeding is important in developing the immune system of infants and has been shown to protect against the development of IBD. The risk of developing an increase in disease activity postpartum is the same regardless of breastfeeding status. Most IBD medications are also considered safe in breastfeeding and have no major risks to infants. Despite this, breastfeeding rates remain low among women with IBD, mostly due to concerns about the safety of IBD therapy with breastfeeding. Many women self-discontinue their IBD medications to breastfeed, and there is often uncertainty among health professionals to make recommendations about therapy. Dedicated IBD clinics can greatly support mothers during pregnancy and breastfeeding periods to enhance their knowledge, optimize their medication adherence, and improve their postpartum outcomes. This review aims to provide the most recent evidence-based literature regarding the safety of breastfeeding in women with IBD and the current recommendations about medical therapies with breastfeeding.

Childhood obesity is a significant global health challenge with rising prevalence over the past 50 years, affecting both immediate and long-term health outcomes. The increase in prevalence from 0.7% to 5.6% in girls and 0.9% to 7.8% in boys highlights the urgency of addressing this epidemic. By 2025, it is estimated that 206 million children and adolescents aged 5-19 years will be living with obesity. This review explores the complex interplay of genomics and genetics in pediatric obesity, transitioning from monogenic and polygenic obesity to epigenetics, and incorporating advancements in omics technologies. The evolutionary purpose of adiposity, systemic evaluation of hyperphagia, and the role of various genetic factors are discussed. Technological advancements in genotyping offer new insights and interventions. The integration of genetic screening into clinical practice for early identification and personalized treatment strategies is emphasized.

Ulcerative colitis (UC), one among other refractory diseases worldwide, has shown an increasing trend of progression to colorectal cancer in recent years. In the treatment of UC, traditional Chinese medicine has demonstrated good efficacy, with a high cure rate, fewer adverse effects, great improvement in the quality of patient survival, and reduction in the tendency of cancerous transformation. It shows promise as a complementary and alternative therapy. This review aims to evaluate and discuss the current research on UC, signaling pathways, and gut microbiota. We also summarized the mechanisms of action of various Chinese medicines (active ingredients or extracts) and herbal formulas, through signaling pathways and gut microbiota, with the expectation that they can provide references and evidence for treating UC and preventing inflammation-associated colorectal cancer by traditional Chinese medicine. We illustrate that multiple signaling pathways, such as TLR4, STAT3, PI3K/Akt, NF-[Formula: see text]B, and Keap1/Nrf2, can be inhibited by Chinese herbal treatments through the combined regulation of signaling pathways and gut microbiota, which can act individually or synergistically to inhibit intestinal inflammatory cell infiltration, attenuate gut oxidative responses, and repair the intestinal barrier.

The search for alternatives to antibiotic growth promoters in poultry production has increased interest in probiotics. However, the complexity of the interactions between probiotics, gut microbiome, and the host hinders the development of effective probiotic interventions. This study explores metabolic modelling to examine the possibility of designing informed probiotic interventions within poultry production.

Genomic metabolic models of fungi were generated and simulated in the context of poultry gut microbial communities. The modelling approach correlated with short-chain fatty acid production, particularly in the caecum. Introducing fungi to poultry microbiomes resulted in strain-specific and diet-dependent effects on the gut microbiome. The impact of fungal probiotics on microbiome diversity and pathogen inhibition varied depending on the specific strain, resident microbiome composition, and host diet. This context-dependency highlights the need for tailored probiotic interventions that consider the unique characteristics of each poultry production environment.

This study demonstrates the potential of metabolic modelling to elucidate the complex interactions between probiotics, the gut microbiome, and diet in poultry. While the effects of specific fungal strains were found to be context-dependent, the approach itself provides a valuable tool for designing targeted probiotic interventions. By considering the specific characteristics of the host microbiome and dietary factors, this methodology could guide the deployment of effective probiotics in poultry production. However, the current work relies on computational predictions, and further in vivo validation studies are needed to confirm the efficacy of the identified probiotic candidates. Nonetheless, this study represents a significant step in using metabolic models to inform probiotic interventions in the poultry industry. Video Abstract.

Toluene diisocyanate (TDI) is a major industrial compound that induces occupational asthma with steroid-resistant properties. Recent studies suggest that the gastrointestinal tract may be an effective target for the treatment of respiratory diseases. However, the alterations of the gut-lung axis in TDI-induced asthma remain unexplored. Therefore, in this study, a model of stable occupational asthma caused by TDI exposure was established to detect the alteration of the gut-lung axis. Exposure to TDI resulted in dysbiosis of the gut microbiome, with significant decreases in Barnesiella_intestinihominis, Faecalicoccus_pleomorphus, Lactobacillus_apodemi, and Lactobacillus_intestinalis, but increases in Alistipes_shahii and Odoribacter_laneus. The largest change in abundance was in Barnesiella_intestinihominis, which decreased from 12.14 per cent to 6.18 per cent. The histopathological abnormalities, including shorter length of intestinal villi, thinner thickness of muscularis, reduced number of goblet cells and inflammatory cell infiltration, were found in TDI-treated mice compared to control mice. In addition, increased permeability (evidenced by significantly reduced levels of ZO-1, Occludin and Claudin-1) and activation of TLR4/NF-κB signaling were observed in the intestine of these TDI-exposed mice. Concurrently, exposure to TDI resulted in airway hyperresponsiveness, overt cytokine production (e.g., IL-4, IL-5, IL-13, IL-25, and IL-33), and elevated IgE level within the respiratory tract. The expression of tight junction proteins is reduced and TLR4/NF-κB signaling is activated in the lung following TDI treatment. In addition, correlation analyses showed that changes in the gut microbiota were correlated with TDI exposure-induced airway inflammation. In conclusion, the present study suggests that the immune gut-lung axis may be involved in the development of TDI-induced asthma, which may have implications for potential interventions against steroid-resistant asthma.

The prevalence of many chronic noncommunicable diseases has been steadily rising over the past six decades. During this time, over 350,000 new chemical substances have been introduced to the lives of humans. In recent years, the epithelial barrier theory came to light explaining the growing prevalence and exacerbations of these diseases worldwide. It attributes their onset to a functionally impaired epithelial barrier triggered by the toxicity of the exposed substances, associated with microbial dysbiosis, immune system activation, and inflammation. Diseases encompassed by the epithelial barrier theory share common features such as an increased prevalence after the 1960s or 2000s that cannot (solely) be accounted for by the emergence of improved diagnostic methods. Other common traits include epithelial barrier defects, microbial dysbiosis with loss of commensals and colonization of opportunistic pathogens, and circulating inflammatory cells and cytokines. In addition, practically unrelated diseases that fulfill these criteria have started to emerge as multimorbidities during the last decades. Here, we provide a comprehensive overview of diseases encompassed by the epithelial barrier theory and discuss evidence and similarities for their epidemiology, genetic susceptibility, epithelial barrier dysfunction, microbial dysbiosis, and tissue inflammation.

This study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC vs healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups, and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified five bacterial guilds dominated by Prevotella, Enterobacteriaceae, Akkermansia, Clostridiales, or Bacteroides. The Bacteroides and Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls, whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes, and very few differentially abundant taxa were observed. Non-negative matrix factorization analysis of the oral microbiota samples identified seven guilds dominated by Veillonella, Prevotella, Gemellaceae, Haemophilus, Neisseria, Propionibacterium, and Streptococcus; however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis.

Emerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC), and none have characterized these microbiomes in women with ductal carcinoma in situ (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.

Inflammatory bowel disease (IBD) is an idiopathic gastrointestinal disease with drastically increasing incidence rates. Due to its multifactorial etiology, a precise investigation of the pathogenesis is extremely difficult. Although reductionist cell culture models and more complex disease models in animals have clarified the understanding of individual disease mechanisms and contributing factors of IBD in the past, it remains challenging to bridge research and clinical practice. Conventional 2D cell culture models cannot replicate complex host-microbiota interactions and stable long-term microbial culture. Further, extrapolating data from animal models to patients remains challenging due to genetic and environmental diversity leading to differences in immune responses. Human intestine organ-on-chip (OoC) models have emerged as an alternative in vitro model approach to investigate IBD. OoC models not only recapitulate the human intestinal microenvironment more accurately than 2D cultures yet may also be advantageous for the identification of important disease-driving factors and pharmacological interventions targets due to the possibility of emulating different complexities. The predispositions and biological hallmarks of IBD focusing on host-microbiota interactions at the intestinal mucosal barrier are elucidated here. Additionally, the potential of OoCs to explore microbiota-related therapies and personalized medicine for IBD treatment is discussed.

Many genitourinary tract disorders could be attributed partly to the microbiota. This study sought to conduct a systematic review of the role of the microbiota in urinary chronic pelvic pain syndrome (UCPPS).

We searched Embase, Scopus, Web of Science, and PubMed with no time, language, or study type restrictions until December 1, 2023. The JBI Appraisal Tool was used to assess the quality of the studies. Study selection followed the PRISMA statement. Studies addressing microbiome variations among patients suffering from interstitial cystitis/bladder pain syndrome (IC/BPS) or chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and a control group were considered eligible.

A total of 21 studies (1 UCPPS, 12 IC/BPS, and 8 CP/CPPS) comprising 1125 patients were enrolled in our final data synthesis. It has been shown that the reduced diversity and discrepant composition of the gut microbiota may partly be attributed to the UCPPS pathogenesis. In terms of urine microbiota, some operational taxonomic units were shown to be elevated, while others became less abundant. Furthermore, various bacteria and fungi are linked to specific clinical features. Few investigations denied UCPPS as a dysbiotic condition.

Urinary and intestinal microbiota appear to be linked with UCPPS, comprising IC/BPS and CP/CPPS. However, given the substantial disparity of published studies, a battery of prospective trials is required to corroborate these findings.

This study was conducted to explore the protective effects of inulin against lipopolysaccharide (LPS)-induced inflammatory response and intestinal barrier dysfunction in broilers. 108 broilers were allocated to 3 treatments: 1) non-challenged broilers (Control, CON); 2) LPS-challenged broilers (LPS); 3) LPS-challenged broilers fed the basal diet supplemented with 15 g/kg of inulin (Inulin + LPS). At 21 d of age, the LPS-challenged groups received an intraperitoneal injection of LPS, and the CON group received an equal volume of saline. After 4 h of LPS exposure, samples of blood, intestinal mucosa and cecal digesta were collected. The results showed that LPS challenge induced systemic inflammation and damaged intestinal barrier function, whereas inulin attenuated LPS-induced production of pro-inflammatory cytokines by inhibiting the activation of TLR4 and NF-κB p65, and enhanced intestinal barrier function. In addition, LPS stimulation caused cecal microbial dysbiosis as shown by increased abundance of pathogenic bacteria including Ruminococcus_torques_group, Escherichia-Shigella and Subdoligranulum, while supplementation of inulin increased abundance of beneficial bacteria Faecalibacterium and Anaeroplasma, and metabolite production including propionate and butyrate concentrations. In conclusion, dietary supplementation of inulin could partially alleviate LPS-induced inflammation and intestinal barrier injury by modulating intestinal microbiota, thereby minimizing growth retardation of broilers. Our results provide a basis for the rational utilization of inulin in alleviating immune stress in broiler production.

The mammalian intestine is colonized by trillions of microorganisms that are collectively referred to as the gut microbiota. The majority of symbionts have co-evolved with their host in a mutualistic relationship that benefits both. Under certain conditions, such as in Crohn's disease, a subtype of inflammatory bowel disease, some symbionts bloom to cause disease in genetically susceptible hosts. Although the identity and function of disease-causing microorganisms or pathobionts in Crohn's disease remain largely unknown, mounting evidence from animal models suggests that pathobionts triggering Crohn's disease-like colitis inhabit certain niches and penetrate the intestinal tissue to trigger inflammation. In this Review, we discuss the distinct niches occupied by intestinal symbionts and the evidence that pathobionts triggering Crohn's disease live in the mucus layer or near the intestinal epithelium. We also discuss how Crohn's disease-associated mutations in the host disrupt intestinal homeostasis by promoting the penetration and accumulation of pathobionts in the intestinal tissue. Finally, we discuss the potential role of microbiome-based interventions in precision therapeutic strategies for the treatment of Crohn's disease.

Background/Objectives: The cause of ulcerative colitis (UC) may be related to commensal bacteria in genetically susceptible patients. We previously demonstrated that triple antibiotic combination therapy induces remission in patients with active UC in randomized controlled trials (RCTs). Now, we investigate changes in the gut microbiota of patients who responded to the antibiotic combination therapy. Methods: Thirty-one patients with UC given ATM/AFM (amoxicillin, metronidazole, and tetracycline or fosfomycin) therapy for two weeks were enrolled in this study. The clinical conditions of these UC patients were evaluated by the partial Mayo score. The gut microbiota was compared via the metagenomic shot gun analysis of fecal samples. Results: Of the 31 patients, 16 and 8 experienced complete and partial remission, respectively, over three months in response to ATM/AFM therapy, whereas ATM/AFM showed no efficacy in 7 patients. The dysbiosis before treatment in the active stage could be associated with increased populations of Bacteroides, Parabacteroides, Rickenella, Clostridium, Flavonifractor, Pelagibacter, Bordetella, Massilia, and Piscrickettsia species. Metagenomic analysis revealed dramatic changes in the gut microbiota at an early stage, that is, just two weeks after starting ATM/AFM therapy. After treatment in the responder group, the populations of bifidobacterium and lactobacilli species were significantly increased, while the population of bacteroides decreased. Conclusions: These results suggest that metagenomic analysis demonstrated a marked change in the gut microbiota after antibiotic combination treatment. In the triple antibiotic combination therapy, remission was associated with an increase in bifidobacterium and lactobacilli species.

Background: Current treatments for inflammatory bowel disease (IBD) are relatively futile and the extended use of drugs may reduce effectiveness. Several probiotic strains have shown promise in relieving/treating IBD symptoms. Objectives: The current study investigated the impact of fermented soymilk with a mixture of probiotic starter cultures containing Lactobacillus rhamnosus, L. casei, L. plantarum, L. acidophilus, Bifidobacterium longum, and B. animalis subsp. lactis in rats with dextran sulfate sodium (DSS)-induced colitis compared to control. Methods: Rats were randomly assigned to five groups (5 rats/group; n = 25): G1: negative normal control; G2: positive control (DSS); G3: DSS with sulfasalazine (DSS-Z); G4: DSS with soymilk (DSS-SM), and G5: DSS with fermented soymilk (DSS-FSM). Parameters monitored included the following: the disease activity index (DAI), macroscopic and histological assessments of colitis, and a fecal microbial analysis performed to assess the severity of inflammation and ulceration. Results: The DSS-FSM rats group exhibited lower DAI scores (p < 0.05) than other treated groups during the induction period. A macroscopical examination revealed no ulceration or swelling in the intestinal mucosa of rats in the DSS-FSM-treated group, resembling the findings in the negative control group. In the positive control (DSS group), the colon tissue showed increased inflammation (p < 0.05), whereas those in the DSS-SM- and DSS-FSM-treated rats groups did not show significant macroscopic scores of colitis. The positive DSS control and DSS-Z groups had crypt erosion and ulceration areas, severe crypt damage, and epithelial surface erosion, which were absent in the negative control and DSS-FSM groups. The counts of Lactobacillus spp. and Bifidobacterium spp. remained stable in both G1 and G5 over 4 weeks. The consumption of fermented soymilk with a mixture of probiotics could minimize the severity of DSS-induced colitis in rats. Conclusion, it was found that fermented soymilk containing Lactobacilli and Bifidobacterium might be an effective vehicle for reducing the severity of DSS-induced colitis in rats.

Faecal microbiota transplantation (FMT) is a developing therapy for disorders related to gut dysbiosis. Despite its growing application, standardised protocols for FMT filtrate preparation and quality assessment remain undeveloped. The viability of bacteria in the filtrate is crucial for FMT's efficacy and for validating protocol execution. We compared two methods-in vitro cultivation and membrane integrity assessment-for their accuracy, reproducibility and clinical applicability in measuring bacterial viability in frozen FMT stool filtrate.

Bacterial viability in stool filtrate was evaluated using (i) membrane integrity through fluorescent DNA staining with SYTO9 and propidium iodide, followed by flow cytometry and (ii) culturable bacteria counts (colony-forming units, CFU) under aerobic or anaerobic conditions.

Using different types of samples (pure bacterial culture, stool of germ-free and conventionally bred mice, native and heat-treated human stool), we refined the bacterial DNA staining protocol integrated with flow cytometry for assessment of bacterial viability in frozen human stool samples. Both the membrane integrity-based and cultivation-based methods exhibited significant variability in bacterial viability across different FMT filtrates, without correlation. The cultivation-based method showed a mean coefficient of variance of 30.3%, ranging from 7.4% to 60.1%. Conversely, the membrane integrity approach yielded more reproducible results, with a mean coefficient of variance for viable cells of 6.4% ranging from 0.2% to 18.2%.

Bacterial viability assessment in stool filtrate using the membrane integrity method offers robust and precise data, making it a suitable option for faecal material evaluation in FMT. In contrast, the cultivation-dependent methods produce inconsistent outcomes.

Inflammatory bowel disease (IBD) and food allergy (FA) increase in tandem, but the potential impact of IBD on FA remains unclear. We sought to determine the role of IBD on FA. We first assessed the changes of FA-related risk factors in dextran sulphate sodium salt (DSS) induced colitis mice model. Then, we evaluated the role of IBD on FA in mice. FA responses were determined using a clinical allergy score, body temperature change, serum antibody levels, cytokines level and mouse mast cell protease 1 (MMCP-1) concentration. Accumulation of regulatory T cells was tested using flow cytometry. Intestinal changes were identified by histology, immunohistochemistry, gene expression and gut microbial community structure. In DSS-induced colitis mice model, we found the intestinal damage, colonic neutrophil infiltration, and downregulation of splenic Th2 cytokines and Tregs in mesenteric lymph nodes (MLN). Moreover, we also found that IBD can alleviate the FA symptoms and lead to the significant downregulation of Th2 cytokines, serum IgE and MMCP-1. However, IBD exacerbates intestinal injury and promotes the gene expression levels of IL-33 and IL-5 in the small intestine, damages the intestinal tissue structure and aggravates intestinal dysbiosis in FA. IBD functions as a double-edged sword in FA. From the perspective of clinical symptoms and humoral immune responses, IBD can reduce FA response by downregulating Th2 cytokines. But from the perspective of the intestinal immune system, IBD potentially disrupts intestinal tolerance to food antigens by damaging intestinal tissue structure and causing intestinal dysbiosis.

Epidemiological and preclinical studies have indicated a factual association between gut microbiota dysbiosis and high incidence of colitis. Dietary polysaccharides can specifically shift the composition of gut microbiome response to colitis. Here we validated the preventive role of polysaccharides from Pericarpium Citri Reticulatae 'Chachiensis' (PCRCP), a well-known traditional Chinese medicine, in colitis induced by dextrose sodium sulfate (DSS) in both rats and mice. We found that treatment with PCRCP not only significantly reduced DSS-induced colitis via down-regulating colonic inflammatory signaling pathways including PI3K-Akt, NLRs and NF-κB, but also enhanced colonic barrier integrity in rats. These protective activities of PCRCP against DSS-induced injuries in rats were in part due to the modulation of the gut microbiota revealed by both broad-spectrum antibiotic (ABX)-deleted bacterial and non-oral treatments. Furthermore, the improvement of PCRCP on colitis was impaired by intestinal neomycin-sensitive bacteria in DSS-exposed mice. Specifically, in vivo and in vitro treatment with PCRCP led to a highly sensible enrichment in the gut commensal Parabacteroides goldsteinii. Administration of Parabacteroides goldsteinii significantly alleviated typical symptoms of colitis and suppressed the activation of PI3K-Akt-involved inflammatory response in DSS-exposed mice. The anti-colitic effects of Parabacteroides goldsteinii were abolished after the activation of PI3K-Akt signaling pathway by lipopolysaccharide treatment in mice exposed to DSS. This study provides new insights into an anti-colitic mechanism driven by PCRCP and highlights the potential prebiotic of Parabacteroides goldsteinii for the prevention of ulcerative colitis.

Intake of dietary fiber is associated with a reduced risk of inflammatory bowel disease. β-Glucan (BG), a bioactive dietary fiber, has potential health-promoting effects on intestinal functions; however, the underlying mechanism remains unclear. Here, we explore the role of BG in ameliorating colitis by modulating key bacteria and metabolites, confirmed by multiple validation experiments and loss-of-function studies, and reveal a novel bacterial cross-feeding interaction.

BG intervention ameliorates colitis and reverses Lactobacillus reduction in colitic mice, and Lactobacillus abundance was significantly negatively correlated with the severity of colitis. It was confirmed by further studies that Lactobacillus johnsonii was the most significantly enriched Lactobacillus spp. Multi-omics analysis revealed that L. johnsonii produced abundant indole-3-lactic acid (ILA) leading to the activation of aryl hydrocarbon receptor (AhR) responsible for the mitigation of colitis. Interestingly, L. johnsonii cannot utilize BG but requires a cross-feeding with Bacteroides uniformis, which degrades BG and produces nicotinamide (NAM) to promote the growth of L. johnsonii. A proof-of-concept study confirmed that BG increases L. johnsonii and B. uniformis abundance and ILA levels in healthy individuals.

These findings demonstrate the mechanism by which BG ameliorates colitis via L. johnsonii-ILA-AhR axis and reveal the important cross-feeding interaction between L. johnsonii and B. uniformis. Video Abstract.

Composed of an elaborate ecosystem of bacteria, fungi, viruses and protozoa residing in the human digestive tract, the gut microbiome influences metabolism, immune modulation, bile acid homeostasis and host defence. Through observational and preclinical data, the gut microbiome has been implicated in the pathogenesis of a spectrum of chronic diseases ranging from psychiatric to gastrointestinal in nature. Until recently, the lack of unequivocal evidence supporting a causal link between gut microbiome and human health outcomes incited controversy regarding its significance. However, recent randomised controlled trial (RCT) evidence in conditions, such as Clostridioides difficile infection, cancer immunotherapy and ulcerative colitis, has supported a causal relationship and has underscored the potential of the microbiome as a therapeutic target. This review delineates the RCT evidence substantiating the potential for a causal relationship between the gut microbiome and human health outcomes, the seminal observational evidence that preceded these RCTs and the remaining knowledge gaps.

Inflammatory bowel disease (IBD) is a challenging condition to cure that can occur at any age. The gut microbiome and intestinal epithelial barrier play a crucial role in the development of IBD. 1,3-Dioleoyl-2-palmitoylglycerol (OPO), the predominant triglyceride in breast milk, is a structural lipid with multiple physiological functions. However, the protective effect of OPO on IBD and its underlying mechanism remains unclear. This study showed that oral administration of OPO markedly ameliorated dextran sulfate sodium (DSS)-induced colitis phenotypes. OPO treatment reduced inflammation levels by suppressing the TLR4-MyD88-NF-κB signaling pathway in colitis mice. Furthermore, OPO treatment improved intestinal epithelial barrier function via promoting epithelial cell proliferation and differentiation, inhibiting cell apoptosis, and upregulating tight junction protein expression. The 16S rRNA gene sequencing revealed that OPO treatment restored microbial alpha diversity and reshaped the microbiota of colitis mice. Therefore, our study revealed that OPO exhibited a protective role in DSS-induced colitis via maintaining intestinal epithelial barrier integrity and modulating gut microbiota. Our results highlight that OPO could be used as effective supplements for individuals with IBD or intestinal dysfunctions.

Current therapy for patients suffering from inflammatory bowel diseases (IBD) is focused on inflammatory mechanisms exclusively and not the dysbiotic microbiota, despite growing evidence implicating a role for intestinal microbes in disease.

Ongoing research into the intestinal microbiota of IBD patients, using new technologies and/or deeper application of existing ones, has identified a number of microorganisms whose properties and behaviors warrant consideration as causative factors in disease. Such studies have implicated both bacteria and fungi in the pathogenesis of disease. Some of these organisms manifest mechanisms that should be amenable to therapeutic intervention via either conventional or novel drug discovery platforms. Of particular note is a deeper characterization of microbial derived proteases and their destructive potential.

Given the steady progress on the mechanistic role of the microbiota in inflammatory diseases, it is reasonable to anticipate a future in which therapeutics targeting microbial derived pathogenic factors play an important role in improving the lives of IBD patients.

Although the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), has not been fully elucidated, accumulating researches suggest that intestinal microbiota imbalance contributes to the development of IBD in patients and animal models. RDP58, a peptide-based computer-assisted rational design, has been demonstrated to be effective in protecting against a wide range of autoimmune and inflammatory diseases. However, the underlying mechanism by which RDP58 protects against IBD mediated by intestinal microbiota has yet to be elucidated.

The colitis model was induced by continuously administering 2.5 % (wt/vol) dextran sodium sulfate (DSS) solution for 7 days. The manifestations of colon inflammation were assessed via daily weight changes, colon length, tumor necrosis factor-alpha (TNF-α) level, disease activity index (DAI) score, pathology score, and intestinal barrier permeability. Intestinal microbiota analysis was carried out by 16S-rRNA sequencing. Colonic short chain fatty acids (SCFAs) and regulatory T cells (Tregs) were also detected. To further confirm the protective effect of RDP58 on intestinal microbiota, broad-spectrum antibiotic cocktail (ABX) treatment and fecal microbial transplantation (FMT) experiment were performed.

Oral administration of RDP58 ameliorated DSS-induced mice colitis by altering the diversity and composition of intestinal microbiota. Notably, RDP58 significantly upregulated SCFAs-producing microbiota, thereby promoting the generation of Tregs. ABX and FMT were performed to verify the above mechanism.

RDP58 ameliorated DSS-induced colitis through altering intestinal microbiota and enhancing SCFAs and Tregs production in intestinal microbiota dependent manner, potentially provide a novel therapy for IBD.

Previous studies have shown the harmful effects of nanoscale particles on the intestinal tracts of organisms. However, the specific mechanisms remain unclear. Our present study focused on examining the uptake and distribution of polystyrene nanoplastics (PS-NPs) in zebrafish larvae, as well as its toxic effects on the intestine. It was found that PS-NPs, marked with red fluorescence, primarily accumulated in the intestine section. Subsequently, zebrafish larvae were exposed to normal PS-NPs (0.2-25 mg/L) over a critical 10-day period for intestinal development. Histopathological analysis demonstrated that PS-NPs caused structural changes in the intestine, resulting in inflammation and oxidative stress. Additionally, PS-NPs disrupted the composition of the intestinal microbiota, leading to alterations in the abundance of bacterial genera such as Pseudomonas and Aeromonas, which are associated with intestinal inflammation. Metabolomics analysis showed alterations in metabolites that are primarily involved in glycolipid metabolism. Furthermore, MetOrigin analysis showed a significant correlation between bacterial flora (Pedobacter and Bacillus) and metabolites (D-Glycerate 2-phosphate and D-Glyceraldehyde 3-phosphate), which are related to the glycolysis/gluconeogenesis pathways. These findings were further validated through alterations in multiple biomarkers at various levels. Collectively, our data suggest that PS-NPs may impair the intestinal health, disrupt the intestinal microbiota, and subsequently cause metabolic disorders.

The pathological changes in inflammatory bowel disease (IBD) include the disruption of intestinal barrier function and the infiltration of pathogenic microbes. The application of an artificial protective barrier at the site of inflammation can prevent bacterial infiltration, promote epithelial cell migration, and accelerate wound healing. In this study, dopamine-modified hyaluronic acid (HA-DA) was developed as a bioadhesive self-cross-linkable hydrogel, which acted as an enteroprotective agent to promote the healing of inflamed intestinal tissue. The adhesion strength HA-DA to mouse colon was 3.81-fold higher than HA. Moreover, HA-DA promoted Caco-2 cell proliferation and migration as well as had a strong physical barrier effect after gelation. After oral administration, the HA-DA reduced weight loss and attenuated impaired goblet cell function in mice with dextran sodium sulfate-induced IBD. In addition, HA-DA promoted restoration of the epithelial barrier by the upregulation of tight junction proteins. The results reported herein substantiated that self-cross-linkable hydrogel-based enteroprotective agents are a promising approach for the treatment of IBD.

Bile acids are steroids formed at the interface of host metabolism and intestinal microbiota. While primary bile acids are generated in the liver from cholesterol metabolism, secondary bile acids represent the products of microbial enzymes. Close to 100 different enzymatic modifications of bile acids structures occur in the human intestine and clinically guided metagenomic and metabolomic analyses have led to the identification of an extraordinary number of novel metabolites. These chemical mediators make an essential contribution to the composition and function of the postbiota, participating to the bidirectional communications of the intestinal microbiota with the host and contributing to the architecture of intestinal-liver and -brain and -endocrine axes. Bile acids exert their function by binding to a group of cell membrane and nuclear receptors collectively known as bile acid-regulated receptors (BARRs), expressed in monocytes, tissue-resident macrophages, CD4+ T effector cells, including Th17, T regulatory cells, dendritic cells and type 3 of intestinal lymphoid cells and NKT cells, highlighting their role in immune regulation. In this review we report on how bile acids and their metabolitesmodulate the immune system in inflammations and cancers and could be exploiting for developing novel therapeutic approaches in these disorders.

Diet plays an integral role in the modulation of the intestinal environment, with the potential to be modified for management of individuals with inflammatory bowel disease [IBD]. It has been hypothesised that poor 'Western-style' dietary patterns select for a microbiota that drives IBD inflammation and, that through dietary intervention, a healthy microbiota may be restored. This study aimed to systematically review the literature and assess current available evidence regarding the influence of diet on the intestinal microbiota composition in IBD patients, and how this may affect disease activity.

MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library were searched from January 2013 to June 2023, to identify studies investigating diet and microbiota in IBD.

Thirteen primary studies met the inclusion criteria and were selected for narrative synthesis. Reported associations between diet and microbiota in IBD were conflicting due to the considerable degree of heterogeneity between studies. Nine intervention studies trialled specific diets and did not demonstrate significant shifts in the diversity and abundance of intestinal microbial communities or improvement in disease outcomes. The remaining four cross-sectional studies did not find a specific microbial signature associated with habitual dietary patterns in IBD patients.

Diet modulates the gut microbiota, and this may have implications for IBD; however, the body of evidence does not currently support clear dietary patterns or food constituents that are associated with a specific microbiota profile or disease marker in IBD patients. Further research is required with a focus on robust and consistent methodology to achieve improved identification of associations.

There is agreement that inflammatory bowel diseases are, both in terms of species composition and function, associated with an altered intestinal microbiome. This is usually described by the term "dysbiosis," but this is a vague definition lacking quantitative precision. In this brief narrative review, the evidence concerning the primary or secondary role of this dysbiotic state is critically evaluated. Among others, the following facts argue against a primary etiological impact: 1) There is no specific dysbiotic microbiome in IBD, 2) the presence or absence of mucosal inflammation has a profound impact on the composition of the microbiome, 3) dysbiosis is not specific for IBD but linked to many unrelated diseases, 4) antibiotics, probiotics, and microbiome transfer have a very limited therapeutic effect, 5) the microbiome in concordant twins is similar to disease-discordant twins, and 6) the microbiome in relatives of IBD patients later developing IBD is altered, but these individuals already display subclinical inflammation.

Recent advances in understanding how the microbiome can influence both the physiology and the pathogenesis of disease in humans have highlighted the importance of gaining a deeper insight into the complexities of the host-microbial dialogue. In tandem with this progress, has been a greater understanding of the biological pathways which regulate both homeostasis and inflammation at barrier tissue sites, such as the skin and the gut. In this regard, the Interleukin-1 family of cytokines, which can be segregated into IL-1, IL-18 and IL-36 subfamilies, have emerged as important custodians of barrier health and immunity. With established roles as orchestrators of various inflammatory diseases in both the skin and intestine, it is now becoming clear that IL-1 family cytokine activity is not only directly influenced by external microbes, but can also play important roles in shaping the composition of the microbiome at barrier sites. This review explores the current knowledge surrounding the evidence that places these cytokines as key mediators at the interface between the microbiome and human health and disease at the skin and intestinal barrier tissues.