The perturbation of the symbiotic relationship between microbes and intestinal immune system contributes to gut inflammation and Inflammatory Bowel Disease (IBD) development. The host mucosa glycans (glycocalyx) creates a major biological interface between gut microorganisms and host immunity that remains ill-defined. Glycans are essential players in IBD immunopathogenesis, even years before disease onset. However, how changes in mucosa glycosylation shape microbiome and how this impact gut immune response and inflammation remains to be clarified. Here, we revealed that alterations in the expression of complex branched N-glycans at gut mucosa surface, modeled in glycoengineered mice, resulted in dysbiosis, with a deficiency in Firmicutes bacteria. Concomitantly, this mucosa N-glycan switch was associated with a downregulation of type 3 innate lymphoid cells (ILC3)-mediated immune response, leading to the transition of ILC3 toward an ILC1 proinflammatory phenotype and increased TNFα production. In addition, we demonstrated that the mucosa glycosylation remodeling through prophylactic supplementation with glycans at steady state was able to restore microbial-derived short-chain fatty acids and microbial sensing (by NOD2 expression) alongside the rescue of the expression of ILC3 module, suppressing intestinal inflammation and controlling disease onset. In a complementary approach, we further showed that IBD patients, often displaying dysbiosis, exhibited a tendency of decreased MGAT5 expression at epithelial cells that was accompanied by reduced ILC3 expression in gut mucosa. Altogether, these results unlock the effects of alterations in mucosa glycome composition in the regulation of the bidirectional crosstalk between microbiota and gut immune response, revealing host branched N-glycans/microbiota/ILC3 axis as an essential pathway in gut homeostasis and in preventing health to intestinal inflammation transition.

Inflammatory bowel disease (IBD) is characterized by a disruption of intestinal homeostasis, chronic inflammation, and dysbiosis. Prebiotic supplementation may be useful for managing IBD in dogs. The aim of the study is to investigate the effects of two prebiotics, Biolex MB40 or Leiber Beta-S, on the gut microbiota isolated from three dogs with IBD, using the Colon-on-a-plate technology. Biolex MB40 and Leiber Beta-S contain concentrated 1,3-1,6- β-D-glucan isolated from the Saccharomyces cerevisiae cell walls. Biolex MB40 also contains mannan-oligosaccharide (MOS). Wells of the Colon-on-a-plate set up were inoculated with fecal suspensions and supplemented with either Biolex MB40 and Leiber Beta-S, or no test product (blank). Following 48h incubation, bacterial metabolites were measured and 16S rRNA targeted gene sequencing was performed. Colonic supernatants were added to a Caco-2/THP1 co-culture model to evaluate their effects on barrier integrity upon inflammation-induced barrier disruption and interleukin (IL)-10 production. Acetate and propionate concentrations were significantly increased versus blank with Biolex MB40, and biologically relevant numerical increases were observed with Leiber Beta-S supplementation. A donor-dependent, biologically relevant increase in butyrate was observed with both test products versus blank. Alpha diversity and microbiota biomass were increased, as well as the abundance of the five predominant phyla with both test products relative to blank. The greatest increases in abundance were observed for the Bacteroidetes and Firmicutes phyla. Fermentation of both test products had a protective effect on the gut epithelial barrier (measured by transepithelial electrical resistance) that was donor dependent. IL-10 production was significantly increased with Biolex MB40 supplementation for all donors, and with Leiber Beta-S supplementation for one donor. These in vitro findings confirm a prebiotic effect for both products and suggest that supplementation with either Biolex MB40 or Leiber Beta-S may have beneficial effects on the gut microbiota of dogs with IBD.

Administering beneficial bacteria as probiotics to restore the intestinal microbiota and its metabolic functions, such as butyrogenesis, is a promising treatment strategy in ulcerative colitis (UC). This study aimed to investigate the effect of a combination of probiotics, consisting of the lactic acid bacterium Weizmannia coagulans SANK70258 and the lactate-utilizing butyrate-producing bacteria Anaerostipes caccae or Clostridium butyricum, on the colonic environment using an in vitro colonic microbiota culture model with fecal inoculums from seven patients with UC. Co-inoculated W. coagulans and A. caccae neither inhibited each other's growth nor significantly affected the relative abundance of other bacterial species; however, the growth of W. coagulans was significantly inhibited when co-inoculated with C. butyricum. The relative abundance of pro-inflammatory bacteria (Escherichia sp. and unclassified Enterobacteriaceae) and Bifidobacterium spp. significantly decreased in W. coagulans-C. butyricum co-inoculated cultures. Inoculation with any of the probiotics alone did not increase butyrate production, whereas co-inoculation of W. coagulans with A. caccae or C. butyricum significantly increased the butyrate levels. Overall, the results suggested that W. coagulans and lactate-utilizing butyrate-producing bacteria in combination have synergistic effects through cross-feeding and can effectively restore butyrogenesis in the colonic environment of patients with UC. KEY POINTS: • Effects of probiotics were evaluated using in vitro microbiota model of UC colon. • W. coagulans and lactate-utilizing butyrate producers have synergistic effects. • Co-inoculation of W. coagulans with A. caccae or C. butyricum enhanced butyrogenesis.

Beetroot (Beta vulgaris L.) is well known for its medicinal uses, particularly in managing gastrointestinal disorders. This study investigates the protective effects of fresh red beet juice (FBRJ) on gastrointestinal complications caused by co-administration of dextran sulfate sodium (DSS) and loperamide (LOP), which induce ulcerative colitis and constipation, respectively.

Adult rats were divided into groups and subjected to a 7-day treatment with 5% DSS to induce ulcerative colitis, followed by LOP (3 mg/kg, body weight [b.w.]) for 7 days to cause constipation. FBRJ (5 and 10 mL/kg, b.w.) or yohimbine (YOH) (2 mg/kg, b.w.) was administered 1 h after LOP each day for 7 days. Therapeutic outcomes were evaluated based on macroscopic and histological changes in the gastrointestinal tract, gastric emptying, gastrointestinal transit, oxidative stress parameters, and inflammatory markers.

FBRJ significantly alleviated gastrointestinal dysfunctions caused by DSS and/or LOP, improving both gastric emptying and gastrointestinal transit in a dose-dependent manner (p < 0.05). Specifically, compared with the ulcerative/constipated group, the animals treated with the FBRJ showed a significant increase (52.43% ± 4.65% to 66.23% ± 6.78%) of gastric emptying (GE) andgastrointestinal transit (GIT: 48.08% ± 3.32% to 62.46% ± 4.98%) in a dose-dependent manner. It also modulated antioxidant defense systems by inducing enzyme activities and reducing lipid peroxidation, which had been significantly disrupted by the combined effects of DSS and LOP. Furthermore, inflammatory markers, including C-reactive protein (CRP), pro-inflammatory cytokines, and white blood cell counts, were significantly reduced in both plasma and colonic mucosa.

We suggest that FBRJ significantly protects against DSS-induced colitis and LOP-induced constipation, involving several mechanisms such as increasing secretion and peristaltic activity, reducing inflammation, and preserving the antioxidant properties.

The microbiota in humans consists of trillions of microorganisms that are involved in the regulation of the gastrointestinal tract and immune and metabolic homeostasis. The gut microbiota (GM) has a prominent impact on the pathogenesis of metabolic syndrome (MetS). This process is reciprocal, constituting a crosstalk process between the GM and MetS. In this review, GM directly or indirectly inducing MetS via the host-microbial metabolic axis has been systematically reviewed. Additionally, the specifically altered GM in MetS are detailed in this review. Moreover, short-chain fatty acids (SCFAs), as unique gut microbial metabolites, have a remarkable effect on MetS, and the role of SCFAs in MetS-related diseases is highlighted to supplement the gaps in this area. Finally, the existing therapeutics are outlined, and the superiority and shortcomings of different therapeutic approaches are discussed, in hopes that this review can contribute to the development of potential treatment strategies.

Chronic metabolic inflammation is a common mechanism linked to the development of metabolic disorders such as obesity, diabetes, and cardiovascular disease (CVD). Chronic metabolic inflammation often related to alterations in gut homeostasis, and pathological processes involve the activation of endotoxin receptors, metabolic reprogramming, mitochondrial dysfunction, and disruption of intestinal nuclear receptor activity. Recent investigations into homeostasis and chronic metabolic inflammation have revealed a novel mechanism which is characterized by a timing interaction involving multiple components and targets. This article explores the positive impact of tea consumption on metabolic health of populations, with a special focus on the improvement of inflammatory indicators and the regulation of gut microbiota. Studies showed that tea consumption is related to the enrichment of gut microbiota. The relative proportion of Firmicutes/Bacteroidetes (F/B) is altered, while the abundance of Lactobacillus, Bifidobacterium, and A. muciniphila increased significantly in most of the studies. Thus, tea consumption could provide potential protection from the development of chronic diseases by improving gut homeostasis and reducing chronic metabolic inflammation. The direct impact of tea on intestinal homeostasis primarily targets lipopolysaccharide (LPS)-related pathways. This includes reducing the synthesis of intestinal LPS, inhibiting LPS translocation, and preventing the binding of LPS to TLR4 receptors to block downstream inflammatory pathways. The TLR4/MyD88/NF-κB p65 pathway is crucial for anti-metaflammatory responses. The antioxidant properties of tea are linked to enhancing mitochondrial function and mitigating mitochondria-related inflammation by eliminating free radicals, inhibiting NLRP3 inflammasomes, and modulating Nrf2/ARE activity. Tea also contributes to safeguarding the intestinal barrier through various mechanisms, such as promoting the synthesis of short-chain fatty acids in the intestine, activating intestinal aryl hydrocarbon receptor (AhR) and farnesoid X receptor (FXR), and improving enteritis. Functional components that improve chronic metabolic inflammation include tea polyphenols, tea pigments, TPS, etc. Tea metabolites such as 4-Hydroxyphenylacetic acid and 3,4-Dihydroxyflavan derivatives, etc., also contribute to anti-chronic metabolic inflammation effects of tea consumption. The raw materials and processing technologies affect the functional component compositions of tea; therefore, consuming different types of tea may result in varying action characteristics and mechanisms. However, there is currently limited elaboration on this aspect. Future research should conduct in-depth studies on the mechanism of tea and its functional components in improving chronic metabolic inflammation. Researchers should pay attention to whether there are interactions between tea and other foods or drugs, explore safe and effective usage and dosage, and investigate whether there are individual differences in the tea-drinking population leading to different effects of tea intervention. Ultimately, the application of tea drinking could be a universal therapy for regulating intestinal homeostasis, anti-chronic metabolic inflammatory responses, and promoting metabolic health.

Perturbations of the gut microbiota in patients with inflammatory bowel disease (IBD) have been extensively characterised, but changes to the oral microbiome remain understudied. This study aimed to evaluate the oral microbiome of adults with IBD and of matched controls.

Saliva samples and data were obtained from a Canadian population cohort (n = 320). The salivary microbiome was characterised using 16S rRNA gene sequencing and examined for differences between control participants and those with IBD, as well as disease subcategories (Crohn's Disease and Ulcerative Colitis).

Alpha diversity was significantly lower in participants with IBD than controls in unadjusted models and many remained significant after adjusting for covariates. Significant differences in some beta diversity metrics between participants with IBD and controls were found, although these did not remain significant when adjusted for covariates. Ten genera were significantly differentially abundant between cases and controls. Veillonella and Streptococcus were both increased in abundance in IBD cases vs controls (25% vs 22% and 14% vs 12%, respectively).

These results showcase changes in oral microbial diversity and composition in those living with IBD and highlight the potential of using the salivary microbiome as a biomarker for screening or monitoring IBD.

Inflammatory bowel disease (IBD) is a chronic condition with no cure. Probiotics may offer a new strategy for the treatment of IBD. Weissella confusa has been shown to have antibacterial, anti-inflammatory, and antioxidant beneficial effects in animal models. However, the anti-inflammatory effect of W. confusa at host cellular level and their effect on the gut microbiota are unclear. This study aimed to investigate the effects of W. confusa Wc1982 on inflammation and gut microbiota alterations in a dextran sulfate sodium (DSS) induced colitis mouse model.

Female C57BL/6J mice were randomly divided into control, DSS, and Wc1982 groups (n = 6/group). The Wc1982 group was given continuous gavage of W. confusa Wc1982 for 14 days with the last 7 days also treated with 3% DSS. Disease phenotypes including daily body weight, disease activity index (DAI), colon length and histological changes were evaluated. The composition of colon flora, α-diversity and β-diversity were analyzed by 16S rRNA sequencing. The colonic gene expression profile was analyzed by RNA-seq, and serum and colonic proinflammatory cytokines were assessed by enzyme-linked immunosorbent assay. Analysis of variance (ANOVA) was used to analyze the differences among groups, and Spearman rank test was used to calculate the correlation between species relative abundance and pro-inflammatory markers.

Compared with DSS group, W. confusa Wc1982 significantly improved the disease phenotypes of colitis mice including decreased DAI and pathological score and reduced colon shortening, decreased colonic IL-17, IL-6, and TNF-α levels and serum lipopolysaccharide (p < 0.05), and downregulated the expression of key genes of IL-17 pathway (Lcn2, Mmp3, Mmp13, Ptgs2; p < 0.05). W. confusa Wc1982 modified the gut microbiota community of colitis mice, with increased α-diversity, increased abundance of W. confusa and Akkermansia muciniphila, and decreased abundance of Enterococcus faecalis and Escherichia coli (all p < 0.05).

Supplementation with W. confusa Wc1982 offers a promising strategy for alleviating colitis.

Enterohemorrhagic Escherichia coli (EHEC) and dyspeptic diarrhea are significant health concerns in calves, leading to substantial economic losses in the livestock industry. This study investigated the impact of EHEC infection and dyspeptic diarrhea on calf health, focusing on blood parameters, fecal microbiota, and metabolite profiles. Thirty-two holstein calves were divided into three groups: healthy group (C Group), EHEC-infected group (E Group), and indigestion-induced diarrhea group (I Group). Significant alterations in diarrheic calves were noted in peripheral blood parameters, including hematological, biochemical, and blood gas indices. And then fecal microbiota analysis revealed decreased diversity, with reduced Actinobacteria and increased Proteobacteria and Fusobacteriota in E and I group. Metabolomic profiling showed significant reductions in organic acids and lipids in diarrheic calves. The study concludes that microbial and metabolic alterations play critical roles in the pathogenesis of EHEC- and indigestion-induced diarrhea, with Scorzoside identified as a potential biomarker for differentiating healthy calves from those with diarrhea. These findings provide insights for designing targeted interventions to enhance gut health and reduce disease burden in the livestock.

Fecal microbiota transplantation (FMT) has been shown to restore gut microbiome composition with an acceptable safety profile. FMT in inflammatory bowel disease, specifically ulcerative colitis (UC), has been investigated. We aimed to assess the efficacy of FMT in inducing UC remission.

PubMed, Scopus, Google Scholar, and clinicaltrials.gov were searched for randomized control trials that assessed FMT in inducing UC remission. The primary outcome was combined clinical and endoscopic remission. Secondary outcomes were clinical remission, endoscopic remission, post-treatment overall adverse events, and colitis. Sensitivity analyses, meta-regression, bias assessment, and grading of certainty of evidence were performed.

A total of 14 studies including 600 patients (55.8% male; median age 40.7 years) were assessed. FMT was used in 299 patients and associated with significantly higher odds of combined clinical and endoscopic remission (OR 2.25, 95% CI 1.54, 3.3; p < 0.0001), clinical remission (OR 2.02, 95% CI 1.4, 2.93; p = 0.0002), and endoscopic remission (OR 1.95, 95% CI 1.17, 3.28; p = 0.011). The odds of post-treatment overall adverse events (OR 1.24, 95% CI 0.79, 1.95; p = 0.34) and colitis (OR 0.85, 95% CI 0.52, 1.93; p = 0.512) were similar between groups. Compared with baseline, FMT was more effective when biologics (OR 2.71), steroids (OR 2.27), or methotrexate (OR 3.07) were used as pre-FMT treatment. Oral delivery of FMT (OR 3.15) and pooled donors (OR 3.32) led to higher odds of remission. On meta-regression, pooled donors and methotrexate pre-treatment were associated with an increased likelihood of remission.

FMT is promising in inducing UC remission. Administration of medical treatments before FMT may help achieve higher remission rates. Current evidence shows that oral delivery of FMT and multidonor FMT may confer better results.

Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, arise from various factors such as dietary, genetic, immunological, and microbiological influences. The gut microbiota plays a crucial role in the development and treatment of IBD, though the exact mechanisms remain uncertain. Current research has yet to definitively establish the beneficial effects of the microbiome on IBD. Bacteria and viruses (both prokaryotic and eukaryotic) are key components of the microbiome uniquely related to IBD. Numerous studies suggest that dysbiosis of the microbiota, including bacteria, viruses, and bacteriophages, contributes to IBD pathogenesis. Conversely, some research indicates that bacteria and bacteriophages may positively impact IBD outcomes. Additionally, plant metabolites play a crucial role in alleviating IBD due to their anti-inflammatory and microbiome-modulating properties. This systematic review discusses the role of the microbiome in IBD pathogenesis and evaluates the potential connection between plant metabolites and the microbiome in the context of IBD pathophysiology.

Inflammatory bowel disease (IBD) is a multifactorial illness with a climbing prevalence worldwide. While biologics are commonly prescribed especially for severe cases, they may worsen patients' outcomes due to financial burden. Consequently, there has been an increased focus on biosimilars to improve overall disease outcomes by maintaining similar efficacy and safety while minimizing the cost of therapy. Infliximab-dyyb was the first biosimilar approved by US-FDA for IBD. Since that, the US-FDA approved 14 biosimilars with different mechanisms of action and different routes of administration for IBD patients (four infliximab biosimilars, nine adalimumab biosimilars, and most recently one ustekinumab biosimilar). It should be noted that more biologics are in the pipeline as golimumab and natalizumab patents are set to expire in the near future, and biosimilars are now in pre-clinical to phase 3 trials. Different studies have evaluated biologics' effectiveness and safety and concluded that the majority of available biosimilars are efficacious and have similar adverse effect profiles compared to their reference biologics. It is worth mentioningthat post-marketing surveillance reports revealed some risks associated with biosimilars which should be taken into consideration in future research and clinical trials to avoid health hazards. Most biologics and biosimilars are administered parenterally which results in several drawbacks such as raised risk of infections, hypersensitivity, autoimmunity, development of malignancies, liver toxicity as well as worsening of heart failure. Several drug delivery systems based on passive and active targeting mechanisms are under active investigation to overcome these limitations. This review sheds light on the emergence of biologics and biosimilars as alternatives in IBD management, the differences between them, challenges and risks, and future perspectives in IBD therapy and new trends in drug delivery systems.

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.

Irritable bowel syndrome (IBS) is a disorder characterized by microbiota-neuroimmune interaction resulting in disturbance to the gut-brain axis (GBA). The purpose of this review is to garner an overview of the different pathophysiological mechanisms indicated in the development of IBS and the associated sequalae on gut microbiota alongside its role in the GBA. Moreover, we aim to provide an insight into the possibility of utilizing personalized medicine when managing said affected populations.

A comprehensive review was performed of the relevant literature pertaining to the current state of GBA alteration implicated in IBS, comprising microbiota-neuroimmune interaction alongside disturbance and activation, respectively. Different search databases were utilized, including PubMed/MEDLINE and ScienceDirect.

The review demonstrated the most evident etiologies of IBS being the imbalance of microbiota and the alteration to the GBA. Furthermore, the interrelation between microbiota and neuroimmunity was discussed. Promising avenues for IBS prevention and management are offered through emerging research on the pathophysiological mechanisms indicated in IBS-associated GBA alteration. This entails a role for the involved interactions between microbiota modification and neuroimmunity activation.

Promising prospects for symptom prevention and management are signaled by the possibility of personalized therapy specifically designed to address the GBA dysfunction indicated in IBS. Policymakers and developers should encourage further study and allocate available resources to aid researchers in the implementation and identification of novel preventive therapeutics. Furthermore, physicians should advocate and integrate the use of personalized medical approaches of IBS to help ensure a better quality of life.

Crohn's disease (CD) and ulcerative colitis (UC), referred to as inflammatory bowel disease (IBD), pose considerable challenges in treatment because they are chronic conditions that easily relapse. The occurrence of IBD continues to rise in developing countries. Nonetheless, the existing therapies for IBD have limitations and fail to address the needs of the patients thoroughly. There is an increasing need for new, safe, and highly effective alternative medications for IBD patients. Traditional Chinese Medicine (TCM) is employed in drug development and disease management due to its wide-range of biological activities, minimal toxicity, and limited side effects. Extensive research has shown that certain TCM exhibits significant therapeutic benefits for IBD treatments. Honeysuckle (Lonicera japonica) was used in TCM research and clinical settings for the treatment of IBD. Bioactive metabolites in L. japonica, such as luteolin, quercetin, cyanidin, chlorogenic acid (CGA), caffeic acid (CA), and saponin, exhibit significant therapeutic benefits for managing IBD. The honeysuckle flower is a potential candidate in the treatment of IBD due to its anti-inflammatory, immune system-regulating, and antioxidant qualities. This paper reviews the metabolites of the honeysuckle flower as a candidate for the treatment of IBD. It discusses the fundamental mechanism of L. japonica and the potential of its bioactive metabolites in the prevention and treatment of IBD.

T cell metabolism and differentiation significantly shape the initiation, progression, and resolution of inflammatory responses. Upon activation, T cells undergo extensive metabolic shifts to meet distinct functional demands across various inflammatory stages. These metabolic alterations are not only critical for defining different T cell subsets, but also for sustaining their activity in inflammatory environments. Key signaling pathways-including mTOR, HIF-1α, and AMPK regulate these metabolic adaptions, linking cellular energy states with T cell fate decisions. Insights into the metabolic regulation of T cells offer potential therapeutic strategies to manipulate T cell function, with implications for treating autoimmune diseases, chronic inflammation, and cancer by targeting specific metabolic pathways.

Despite advances in cancer treatment, the development of effective therapies remains an urgent unmet need. Here, we investigate the potential of bacteria-derived metabolites as a therapeutic alternative for the treatment of cancer. We detect 3-hydroxydodecanedioic acid in the serum of tumor-bearing mice treated with serum from mice previously supplemented with a mix of Clostridiales bacteria. Further, 3-hydroxydodecanoic acid, an intermediate derivative between dodecanoic and 3-hydroxydodecanedioic acids, exhibits a strong anti-tumor response via GPR84 receptor signaling and enhances CD8+ T cell infiltration and cytotoxicity within tumor tissue in multiple cancer models. Metabolomics analysis of colorectal cancer patient serum reveals an inverse correlation between the abundance of these metabolites and advanced disease stages. Our findings provide a strong rationale for 3-hydroxydodecanoic acid and the GPR84 receptor to be considered as promising therapeutic targets for cancer treatment.

Inflammatory bowel disease (IBD) is a chronic condition that includes two main types, Crohn's disease (CD) and ulcerative colitis (UC), involving inflammation of the gastrointestinal (GI) tract. The exact cause of IBD is unknown but could be a combination of genetic, environmental, and immune system factors. This study investigated the impact of IBD on microbiota diversity by evaluating the differences in microbial composition and the microbiota of a control group (A) of healthy individuals and a group (B) of IBD patients. Sixty biopsies were collected from participants recruited from hospitals in Makkah, Saudi Arabia. Biopsy specimens were taken during colonoscopy examination, and bacterial identification was performed by extracting ribosomal DNA from sigmoid colon biopsies using a DNeasy Blood & Tissue Kit. Metagenomics and bioinformatics analyses were then conducted to analyze and compare the microbiota in the two groups. The results showed that the varieties of core microbiome species were 3.81% greater in the IBD patients than in the members of the control group. Furthermore, the differences between the groups were significantly greater than the variations within each group. Differences between the two groups were detected in the relative abundance of Clostridium nexile, Ruminococcus gnavus, Ruminococcus faecis, and Escherichia coli. These results indicate that microbiota could play a role in the pathogenesis of IBD and suggest that microbial diversity can serve as a biomarker for diagnosing the disease and monitoring its progression.

Background: The role of gut dysbiosis in the pathophysiology of atopic dermatitis (AD) through immune system (IS) imbalance is a novel line of investigation currently under discussion. This study aimed to characterize compare the composition and functional profile of the gut microbiota (GM) between adults with AD and healthy individuals. Methods: Observational cross-sectional study, where fecal samples from 70 adults (38 patients and 32 controls) were analyzed using metagenomics and bioinformatics. Results: Differences between the GM of patients with AD and healthy individuals were demonstrated. Reduced microbial diversity was found in subjects with AD. Bacterial species with lower abundance primarily belonged to the families Ruminococcaceae, Akkermansiaceae, and Methanobacteriaceae. Several microbial metabolic pathways were found to be decreased in patients with AD, including amino acid biosynthesis, vitamin biosynthesis, fatty acids and lipids biosynthesis, and energy metabolism. Conclusion: Adults with AD exhibited a distinct GM compared to healthy individuals. Changes were demonstrated both compositionally and functionally. Further investigation is mandatory to elucidate the potential link and causal relationship between gut dysbiosis and AD, which may be crucial for a deeper understanding of the disease's pathophysiology and the development of novel therapeutic approaches.

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic, environmental, immunological, and microbial factors; however, it remains unclear. Pro-inflammatory interleukin 8 (IL-8), encoded by the CXCL8 gene, assumes a crucial chemotactic role in leukocyte migration.

This study aimed to investigate whether an association exists between IBD and two CXCL8 variants, namely, c.-251A>T (rs4073) and c.91G>T (rs188378669), and IL-8 concentration. We analyzed the distribution of both variants among 353 Polish IBD patients and 200 population subjects using pyrosequencing, competitive allele-specific PCR and Sanger sequencing.

The c.91T stop-gained allele was significantly more frequent in IBD patients (2.12%) than in controls (0.25%) (p = 0.0121), while the c.-251T allele frequencies were similar (54% vs. 51.5%, p = 0.4955). Serum IL-8 concentrations, measured using ELISA, were higher in IBD patients with the c.91 GG genotype compared to healthy controls (mean, 70.02 vs. 51.5 pg/ml, p<0.01) and patients with c.91 GT (mean, 61.73 pg/ml). Moreover, clinical data indicated that carriers of the c.91T variant need more often corticosteroids and surgical treatment of the disease than GG homozygous IBD patients.

This suggest that the CXCL8 c.91T allele may influence IBD manifestation and the course of the disorders in Polish patients, potentially serving as a novel target for future studies and therapeutic approaches.

Background and Aims: Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) with a globally increasing prevalence, partially driven by alterations in gut microbiota. Although biological therapy is the first-line treatment for CD, a significant proportion of patients experience a primary non-response or secondary loss of response over time. This study aimed to explore the differences in gut microbiota among CD patients with divergent long-term responses to biological therapy, focusing on a long disease course. Methods: Sixteen CD patients who applied the biological agents for a while were enrolled in this study and were followed for one year, during which fecal specimens were collected monthly. Metagenomic analysis was used to determine the microbiota profiles in fecal samples. The response to biological therapy was evaluated both endoscopically and clinically. Patients were categorized into three groups based on their response: R (long-term remission), mA (mild active), and R2A group (remission to active). The differences in the gut microbiota among the groups were analyzed. Results: Significant differences in fecal bacterial composition were observed between the groups. The R2A group exhibited a notable decline in gut microbial diversity compared to the other two groups (p < 0.05). Patients in the R group had higher abundances of Akkermansia muciniphila, Bifidobacterium adolescentis, and Megasphaera elsdenii. In contrast, Veillonella parvula, Veillonella atypica, and Klebsiella pneumoniae were higher in the R2A group. Conclusions: Gut microbial diversity and specific bacterial significantly differed among groups, reflecting distinct characteristics between responders and non-responders.

Background: Reduction of Faecalibacterium prausnitzii abundance is related to inflammatory bowel diseases (IBDs), and supplement of it exists protective effects. Aim: This study aimed to establish a F. prausnitzii-colonized mouse model and investigate that the presence of F. prausnitzii in the gut can ameliorate the severity of dextran sulfate sodium (DSS)-induced colitis. Methods: A F. prausnitzii (ATCC 27768) strain was maintained on the PS-BHI agar plates and manipulated in a strictly anaerobic chamber. A F. prausnitzii-colonized C57BL/6 mice model was tested by a rectal enema with 1 × 109 bacteria/day for 3 days. The 5% DSS was added to drinking water for 3 days to induce colitis and diarrhea in experimental mice. The clinical, cytological, and histological severities were compared between groups. Results: The F. prausnitzii-colonized mice model was successfully established via rectal enema with the property of transfer to offspring. DSS treatment altered gut microbiota and significantly attenuated the abundance of F. prausnitzii in colonized mice. Mice with F. prausnitzii colonization had significantly improved weight loss, anal bleeding, stool consistency, cecum weight, colon length, and serum amyloid A (SAA) level than those without after DSS treatment. Furthermore, the F. prausnitzii-colonized mice significantly reduced the transcription levels of TNF-α, INF-γ and IL-18, and epithelial damage and PMN infiltration in the lamina propria and had better preservation of goblet cells than the control group. Conclusion: We have successfully established a mouse model colonized with F. prausnitzii via rectal enema administration and showed colonization of F. prausnitzii in the gut has a protective effect against DSS-induced colitis.

Acute hepatic injury is a severe condition that is always accompanied by oxidative stress and inflammation, seriously threatening the health of the host. Probiotics have been shown to be involved in the regulation of antioxidant system and gut microbiota activity, but studies on the effects of yak derived Bacillus subtilis (B. subtilis) on acute liver injury and oxidative stress remain scarce. Here, we aim to explore the ameliorative effects of B. subtilis isolated from yaks on oxidative stress and hepatic injury caused by D-galactose, as well as the underlying processes. Results indicated that B. subtilis administration, particularly the BS3, significantly mitigated hepatic damage induced by D-galactose in mice as evidenced by ameliorating liver tissue damage as well as decreasing ALT (p < 0.05) and AST (p < 0.05) levels. Additionally, the B. subtilis intervention was demonstrated to enhance the antioxidant system in D-galactose-exposed mice, as manifested by increased T-AOC and SOD, alongside a decrease in MDA levels (p < 0.05). Meanwhile, B. subtilis intervention could effectively mitigate oxidative damage via modulating the Keap1/Nrf2 signaling pathway. Importantly, B. subtilis exhibited a pronounced protective effect against D-galactose-induced intestinal barrier dysfunction through improving tight junction proteins. The gut microbiota results suggest that BS3 alters the abundance of some gut flora such as Firmicutes phylum and Oscillibacter and Lachnospiraceae_NK4A136 genera, which affects the composition of the gut microbiota and reverses the decrease in the microbial richness index in mice. In summary, these findings demonstrated that B. subtilis isolated from yaks serve as a promising candidate to ameliorate oxidative damage and hepatic injury. Meanwhile, the positive regulation effect of B. subtilis on gut microbiota and intestinal mucosal barrier may be one of its underlying mechanisms to alleviate oxidative stress and hepatic injury.

We aimed to evaluate the diagnostic accuracy of fecal calprotectin (FC) and intestinal ultrasound (IUS), independently and in combination, as screening tools for adults with suspected IBD to reduce the number of unnecessary endoscopic procedures.

We conducted a retrospective monocentric study that included consecutive adult patients with (i) ileocolonoscopy for suspected IBD between January 2021 and June 2023 who had either (ii) IUS and/or (iii) a FC test within 6 weeks. Bowel wall thickness (BWT) and the color Doppler signal (CDS) were evaluated for all segments. The presence of lymphadenopathy, loss of stratification, stricture, and fistula were also recorded.

In total, 119 patients with a median age of 32 years (IQR, 24.0-41.0) were included. The most common symptoms were abdominal pain (n = 88, 75 %) and chronic diarrhea (n = 89, 75 %). Among the 119 patients, 74 (62 %) had IUS, 101 (82 %) had a FC test, and 56 (47 %) had both. Forty patients (34 %) had a diagnosis of IBD, including 31 (26 %) with CD and 9 (8 %) with UC. By ROC curve analysis, the best threshold of FC to diagnose IBD was 117 ug/g (Se 97 %, Sp 73 %, PPV 67 %, NPV 98 %, AUC 0.88, 95 %CI [0.81; 0.94], p = 0.006). Using this threshold, only 3 % of patients were misclassified as non-IBD. Screening by measuring FC levels would result in a 48 % reduction in the number of adults requiring endoscopy. Abnomal IUS was significantly associated with a diagnosis of IBD (OR 5.6, 95 %IC [2.1;16.2], P = 0.0008). The association of a BWT>3 mm and a positive CDS was associated with a Se, Sp, PPV, and NPV of 48 %, 100 %, 100 %, and 75 %, respectively, but 52 % of patients were misclassified as non-IBD. The combination of a BWT>3 mm, CDS, and FC>117 ug/g had a Se, Sp, PPV, and NPV of 44 %, 100 %, 100 %, and 69 %, respectively. For patients with a normal IUS and FC<117 ug/g, 4 % were misclassified as non-IBD.

The combination of FC and IUS is a useful screening strategy to identify patients who truly require endoscopy for suspected IBD. Calprotectin is a highly effective test for ruling out IBD. Conversely, relying solely on IUS lacks the discriminative power to safely rule out IBD. However, it shows a high PPV and is a potent tool for diagnosing IBD.

Inflammatory bowel disease (IBD) represents a group of chronic inflammatory disorders of the gastrointestinal tract. Despite substantial advances in our understanding of IBD pathogenesis, the currently available therapeutic options remain limited in their efficacy and often come with significant side effects. Therefore, there is an urgent need to explore novel approaches for the management of IBD. One promising avenue of investigation revolves around the use of histone deacetylase (HDAC) inhibitors, which have garnered considerable attention for their potential in modulating gene expression and curbing inflammatory responses. This review emphasizes the pressing need for innovative drugs in the treatment of IBD, and drawing from a wealth of preclinical studies and clinical trials, we underscore the multifaceted roles and the therapeutic effects of HDAC inhibitors in IBD models and patients. This review aims to contribute significantly to the understanding of HDAC inhibitors' importance and prospects in the management of IBD, ultimately paving the way for improved therapeutic strategies in this challenging clinical landscape.

Irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) are gastrointestinal disorders, which can be triggered by gut microbiota dysbiosis. The development of IBS-like symptoms has been linked to the overgrowth of Candida spp. In addition, the critical role of fungi has been highlighted in the pathogenesis of IBD. This study investigated the association between Blastocystis and selected yeasts in IBS and IBD patients.

This investigation is a cross-sectional study from 2022 to 2024, performed on 91 participants, including 20 healthy individuals, 27 patients with IBS, and 44 IBD patients [39 with ulcerative colitis (UC; 88.63%) and 5 (11.37%) Crohn's disease (CD)], who were also categorized based on the presence of Blastocystis. Total DNA was extracted from stool samples, and the presence and quantity of yeasts including C. albicans, C. tropicalis, C. glabrata, C. parapsilosis, C. krusei, Geotrichum candidum, Rhodotorula spp., Cryptococcus neoformans, and Saccharomyces cerevisiae were evaluated by real-time PCR. Statistical tests were used to assess significant associations between variables.

Saccharomyces cerevisiae and C. albicans were the most prevalent yeasts in all groups. Candida tropicalis and C. neoformans were identified in neither patients nor healthy subjects. The presence/absence of C. albicans was not significantly different between patients with IBD, IBS, and the control groups. This was similar for G. candidum. However, there was a difference in the presence of S. cerevisiae among patients, although it was insignificant (p-value = 0.077). There was a significant difference in the quantity of C. albicans between IBD (880.421 ± 2140.504), IBS (10.307 ± 15.206), and controls (2875.888 ± 8383.889) (p-value = 0.020). Specifically, the source of difference was seen between IBD patients and the control group (p-value = 0.005). In addition, considering the presence of Blastocystis, a statistically significant association was seen between the number of C. albicans and the sample groups (p-value = 0.013). The quantity of C. albicans was significantly different between IBS and IBD patients.

Regarding the presence of Blastocystis, the quantity of C. albicans and S. cerevisiae was increased and decreased in the studied groups, respectively. This is a preliminary study, and eukaryote-eukaryote association in IBS and IBD patients should be considered in further studies.

Inflammatory bowel disease remains a significant challenge in clinical settings. This study investigated the therapeutic potential of sea cucumber ovum hydrolysates (SCH) in a dextran sulfate sodium (DSS)-induced colitis mouse model. SCH, defined by its elevated stability and solubility, with a molecular weight below 1000 Da, significantly alleviated DSS-induced colitis, as evidenced by enhanced splenic index, reduced colonic damage, and diminished serum pro-inflammatory cytokines. Furthermore, macrogenomic analysis demonstrated that SCH increased beneficial gut microbes and decreased pro-inflammatory bacteria. Furthermore, metabolomic analysis of colonic tissues identified elevated levels of anti-inflammatory metabolites, such as Phenyllactate, 2-Hydroxyglutarate, and L-Aspartic acid, in colitis mice after oral administration of SCH. In conclusion, SCH represents a promising candidate for the treatment of colitis.

Despite combination antiretroviral therapy (ART), HIV causes persistent gut barrier dysfunction, immune depletion, and dysbiosis. Furthermore, ART interruption results in reservoir reactivation and rebound viremia. Both IL-21 and anti-α4β7 improve gut barrier functions, and we hypothesized that combining them would synergize as a dual therapy to improve immunological outcomes in SIV-infected rhesus macaques (RMs). We found no significant differences in CD4+ T cell reservoir size by intact proviral DNA assay. SIV rebounded in both dual-treated and control RMs following analytical therapy interruption (ATI), with time to rebound and initial rebound viremia comparable between groups; however, dual-treated RMs showed slightly better control of viral replication at the latest time points after ATI. Additionally, following ATI, dual-treated RMs showed immunological benefits, including T cell preservation and lower PD-1+ central memory T cell (TCM) frequency. Notably, PD-1+ TCMs were associated with reservoir size, which predicted viral loads (VLs) after ATI. Finally, 16S rRNA-Seq revealed better recovery from dysbiosis in treated animals, and the butyrate-producing Firmicute Roseburia predicted PD-1-expressing TCMs and VLs after ATI. PD-1+ TCMs and gut dysbiosis represent mechanisms of HIV persistence and pathogenesis, respectively. Therefore, combining IL-21 and anti-α4β7 may be an effective therapeutic strategy to improve immunological outcomes for people with HIV.

Individuals with inflammatory bowel disease (IBD) are at a higher risk of developing mental disorders, such as anxiety and depression. The imbalance between the intestinal microbiota and its host, known as dysbiosis, is one of the factors, disrupting the balance of metabolite production and their signaling pathways, leading to disease progression. A metabolomics approach can help identify the role of gut microbiota in mental disorders associated with IBD by evaluating metabolites and their signaling comprehensively. This narrative review focuses on metabolomics studies that have comprehensively elucidated the altered gut microbial metabolites and their signaling pathways underlying mental disorders in IBD patients. The information was compiled by searching PubMed, Web of Science, Scopus, and Google Scholar from 2005 to 2023. The findings indicated that intestinal microbial dysbiosis in IBD patients leads to mental disorders such as anxiety and depression through disturbances in the metabolism of carbohydrates, sphingolipids, bile acids, neurotransmitters, neuroprotective, inflammatory factors, and amino acids. Furthermore, the reduction in the production of neuroprotective factors and the increase in inflammation observed in these patients can also contribute to the worsening of psychological symptoms. Analyzing the metabolite profile of the patients and comparing it with that of healthy individuals using advanced technologies like metabolomics, aids in the early diagnosis and prevention of mental disorders. This approach allows for the more precise identification of the microbes responsible for metabolite production, enabling the development of tailored dietary and pharmaceutical interventions or targeted manipulation of microbiota.

The term "inflammatory bowel disease" (IBD) refers to a group of chronic inflammatory gastrointestinal disorders, which include ulcerative colitis and Crohn's disease. The necessity for alternative therapeutic approaches is underscored by the fact that although present medicines are successful, they frequently result in considerable adverse effects. Naturally occurring substances included in fruits and vegetables called polyphenols have been shown to have the capacity to control important inflammatory pathways including NF-κB and JAK/STAT, which are essential for the pathophysiology of IBD. The processes by which polyphenols, such as curcumin, EGCG, resveratrol, and quercetin, reduce inflammation are examined in this article. Polyphenols may have therapeutic advantages by blocking the synthesis of cytokines and the activation of immune cells by targeting these pathways. Preclinical study indicates a reduction in intestinal inflammation, which is encouraging. However, more clinical research is needed to determine the clinical relevance of polyphenols in the therapy of IBD, especially with regard to their long-term safety and bioavailability.

Microorganisms in the gut play a pivotal role in human health, influencing various pathophysiological processes. Certain microorganisms are particularly essential for maintaining intestinal homeostasis, reducing inflammation, supporting nervous system function, and regulating metabolic processes. Short-chain fatty acids (SCFAs) are a subset of fatty acids produced by the gut microbiota (GM) during the fermentation of indigestible polysaccharides. The interaction between GM and SCFAs is inherently bidirectional: the GM not only shapes SCFAs composition and metabolism but SCFAs also modulate microbiota's diversity, stability, growth, proliferation, and metabolism. Recent research has shown that GM and SCFAs communicate through various pathways, mainly involving mechanisms related to inflammation and immune responses, intestinal barrier function, the gut-brain axis, and metabolic regulation. An imbalance in GM and SCFA homeostasis can lead to the development of several chronic diseases, including inflammatory bowel disease, colorectal cancer, systemic lupus erythematosus, Alzheimer's disease, and type 2 diabetes mellitus. This review explores the synergistic interactions between GM and SCFAs, and how these interactions directly or indirectly influence the onset and progression of various diseases through the regulation of the mechanisms mentioned above.

The inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC) is a complex disease with multifactorial etiology. The intestinal dysbiosis have been investigated to play an important role in IBD pathogenesis and disease activity. The aim of our study was to analyze the intestinal microbiota composition in IBD across different severity levels and the impact of biologic therapy on microbiota modulation.

In this study, 27 IBD patients were recruited, including 14 patients undergoing biologic therapy for moderate to severe disease activity and 13 controls with inactive disease. The gut microbial composition was determined by 16 S ribosomal RNA gene sequencing of stool samples.

Biologic therapy led to significant clinical improvement in IBD disease activity after 48 weeks. About species richness, community alpha diversity was significant lower in active CD patients and enriched gradually after biologic therapy. The beta-diversity regard to the difference of bacterial community composition showed significant difference between patients in biologic and control group. A decrease in Firmicutes and increase in Bacteroidetes abundance were observed in patients with active disease, both in CD and UC. Biologic treatment induced shifts in gut microbiota, with increased Firmicutes and decreased Bacteroidetes, as well as improved F/B ratio gradually after treatment, correlating with disease activity.

Our study suggested that gut microbiota differences changed after biologic therapies among IBD with different disease activity, and a rising Firmicutes/Bacteroidetes ratio could be a potential predictor for disease activity and treatment response monitoring.

Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are associated with mucosal barrier disruption and immune suppression. Administration of Lactiplantibacillus plantarum or Bifidobacterium longum subsp. infantis into the SIV-inflamed gut lumen in vivo resulted in rapid reprogramming of microbial TRP metabolism towards indole-3-lactic acid (ILA) production. This shift accelerated epithelial repair and enhanced anti-viral defenses through induction of IL-22 signaling in mucosal T cells and aryl hydrocarbon receptor activation. Additionally, ILA treatment of human colorectal tissue explants ex vivo inhibited HIV replication by reducing mucosal inflammatory cytokine production and cell activation. Our findings underscore the therapeutic potential of microbial metabolic reprogramming of TRP-to-ILA and mechanisms in mitigating viral pathogenic effects and bolstering mucosal defenses for HIV eradication.

Ulcerative colitis (UC) remains an intractable and relapsing disease featured by intestinal inflammation. The anti-UC activity of Akkermansia muciniphila (AKK), an intestinal microorganism, has been widely investigated. The current work is to explore the impacts of AKK on UC and its possible reaction mechanism. In vivo UC model was induced by dextran sulfate sodium (DSS) and phorbol-12-myristate-13-acetate (PMA)-induced THP-1-M0 and raw264.7 macrophages were treated by lipopolysaccharide (LPS). H&E staining evaluated tissue damage. Inflammatory and oxidative stress levels were assessed by relevant kits. The high-throughput analysis of fatty acids was performed by the LC/MS method. RT-qPCR and Western blot detected related gene expression. Flow cytometry measured cell apoptosis and macrophage polarization. Energy metabolism was detected by ELISA, related assay kits, JC-1 staining, and Western blot. AKK reduced the pathological damage of mice colon tissues, alleviated oxidative stress and inflammatory response, upregulated the expression of Occludin-1 and SCFAs receptors, and stimulated M1 to M2 macrophage polarization in vivo. After FFAR2 was silenced, the promoting role of AKK in the viability and M1 to M2 macrophage polarization and the inhibitory role in oxidative stress, inflammation, apoptosis, energy metabolism disorder, necroptosis, and pyroptosis were both reverted. Conclusively, AKK might mediate SCFAs-SLC52A2/FFAR2 pathways to exert protective activities against intestinal inflammatory response in UC, suggesting that AKK might represent a novel and promising candidate for UC therapy.

Rosavin (RSV) is a naturally occurring compound isolated from Rhodiola species. While RSV has been reported with pharmacological activities of anti-oxidation, anti-inflammation, anti-stress and immunomodulation, its effect on colitis and the underlying mechanisms remain unclear.

This study aims to investigate whether and how RSV alleviated colitis in mice.

The protective effect of RSV (50, 100, 200 mg/kg, p.o.) was investigated in dextran sulfate sodium (DSS) mediated mouse models of acute and chronic colitis. Alterations in fecal microbiota were evaluated by 16S rRNA sequencing. Pseudo germ-free mice achieved by antibiotics treatment were applied to assess the RSV-mediated functional role of gut microbiota in colitis. RNA sequencing was performed to determine RSV-induced colonic response. Primary T cell culture was conducted to examine the effect of RSV on Th17 and Treg differentiation. Whole blood assay, dual luciferase reporter assay, and molecular docking methods were applied to investigate the mechanisms and targets of RSV in Th17 regulation.

Oral RSV significantly relieved DSS-mediated acute and chronic colitis in mice, which recovered body weight loss, reduced disease activity index, alleviated colon injury, inhibited inflammation, suppressed the apoptosis of intestinal epithelia, and maintained intestinal barrier function. Moreover, RSV specifically regulated intestinal microbiota by recovering DSS-mediated microbial changes and elevating beneficial microbes such as Lactobacillus and Akkermansia. Antibiotics treatment experiment showed that the protective role of RSV was at least partially dependent on gut microbiota; however, in vitro incubation showed that RSV did not directly promote the growth of Lactobacillus and Akkermansia strains. Further analysis showed that RSV-mediated genetic alterations in colon were enriched in pathways related to lymphocyte regulation. Additionally, RSV regulated the balance of Th17/Treg in colitis mice. Importantly, RSV inhibited the differentiation of Th17 cell in vitro, suppressed the production of IL-17 by Th17 cells, and downregulated Rorc encoding RORγt and its downstream Il17. RSV significantly inhibited the RORγt transcription activity and bound to its ligand binding domain.

RSV alleviates murine colitis through regulating intestinal immunity. Notably, RSV is identified as a novel regulator of Th17 cells that inhibits RORγt-mediated Th17 differentiation. These findings potentiate the Rhodiola-derived natural chemicals as novel anti-colitis agents.

Synbiotics may be useful to mitigate intestinal diseases such as ulcerative colitis. Here we show that combining 13'-carboxychromanol (δT3-13'), a metabolite of vitamin E δ-tocotrienol (δT3) via omega-oxidation, and Lactococcus lactis subsp. cremori (L. cremoris), but neither agent alone, significantly attenuated dextran sulfate sodium (DSS)-induced fecal bleeding and diarrhea, histologic colitis and interleukin 1β in mice. The combination of δT3-13'+L. cremoris also synergistically prevented DSS-caused compositional changes in gut microbiota and enriched beneficial bacteria including Lactococcus and Butyricicoccus. Interestingly, the anti-colitis effect correlated with the concentrations of δT3-13'-hydrogenated metabolite that contains 2 double bonds on the side chain (δT2-13'), instead of δT3-13' itself. Moreover, in contrast to δT3-13', combining δT3 and L. cremoris showed modest anti-colitis effects and did not prevent colitis-associated dysbiosis. In addition, ex vivo anaerobic incubation studies revealed that gut microbes selected by δT3-13' in the animal study could metabolize this compound to δT2-13' via hydrogenation, which appeared to be enhanced by L. cremoris. Overall, our study demonstrates that combining δT3-13' and L. cremoris can synergically prevent dysbiosis, and may be a novel synbiotic against colitis potentially via promoting δT3-13' metabolizers, which in turn contributes to superior beneficial effects of the combination.

Ulcerative Colitis (UC) known as a sub-category of Inflammatory Bowel Diseases (IBD) is a longterm condition that causes inflammation, irritation, and ulcers in the colon and rectum. Though the precise pathogenesis of UC is not fully understood yet, impaired immune responses and imbalanced intestinal microbiome composition have been regarded as two main key players in colitis pathobiology. As conventional treatments are challenged with limitations and side effects, finding a new therapeutic approach has gained increasing attention. Probiotic bacteria with multifunctional health-promoting properties have been considered novel therapeutic options. There is strong evidence indicating that probiotics exert their therapeutic effects mostly by regulating immune system responses and restoring gut microbiome homeostasis. These results validate the rationale behind the clinical application of probiotics in UC management whether prescribed alone or in combination with conventional therapy. This article explores the pathogenesis of UC, concentrating on the influence of immune dysregulation and intestinal microbiome imbalances. Also, it reviews recent in vitro, in vivo, and clinical studies that have demonstrated the efficacy of Lactobacillus species in decreasing UC symptoms by modifying immune responses, restoring gut microbiota balance, and promoting intestinal barrier function.