Search Results (23)

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with escalating global incidence. Conventional therapies face limitations including substantial costs and adverse effects, while live probiotics pose safety risks in vulnerable populations. Postbiotics—inactivated microorganisms conferring health benefits—offer therapeutic potential without viable bacterial risks. This study investigated inactivated Akkermansia muciniphila AKK PROBIO in dextran sulfate sodium (DSS)-induced colitis mice. Inactivated AKK PROBIO significantly ameliorated disease manifestations, restoring body weight and food intake during days 10–14 (p < 0.01) and reducing Disease Activity Index scores (p < 0.0001). Treatment preserved colonic architecture, enhanced tight junction proteins (Claudin-1, Occludin, ZO-1), and elevated mucin 2 expression. Mechanistically, AKK PROBIO modulated inflammatory responses by increasing anti-inflammatory interleukin-10 (p < 0.05) while decreasing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α (all p < 0.05). 16S rRNA sequencing revealed selective microbiota remodeling with enriched beneficial genera (Ligilactobacillus, Lachnospiraceae_NK4A136_group, Bacteroides, Akkermansia) and depleted pathobionts (Escherichia-Shigella). Functional profiling demonstrated enhanced microbial metabolic capacity in carbohydrate and amino acid metabolism pathways. Gas chromatography–mass spectrometry analysis confirmed elevated short-chain fatty acid production, particularly butyrate and isocaproate (p < 0.05). Correlation analyses revealed interconnected relationships among beneficial microbiota, short-chain fatty acids, and anti-inflammatory mediators, while showing inverse associations with pro-inflammatory cytokines. In summary, our findings demonstrate that inactivated AKK PROBIO alleviates colitis, supporting its development as a safe, food-derived postbiotic. Full article

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) encompasses a spectrum of liver conditions and involves gut–liver axis crosstalk. We aimed to evaluate whether oral vancomycin modifies liver injury and the cecal microbiota in a methionine–choline-deficient (MCD) diet model of NASH. Male C57BL/6J mice (n = 28) were block-randomized to four groups (n = 7 each) for 10 weeks: standard diet (STD); MCD diet; STD + vancomycin (VANC); and MCD + VANC (2 mg/mouse ≈ 50 mg/kg, every 72 h). After 10 weeks, liver tissues were analyzed for histological changes, cytokine levels [interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor beta 1 (TGF-β1)], and immunohistochemical markers [ubiquitin and cytokeratin 18 (CK18)]. Cecal microbiota composition was evaluated with 16S ribosomal RNA (rRNA) sequencing. The MCD reproduced key NASH features (macrovesicular steatosis, lobular inflammation). Vancomycin shifted steatosis toward a microvesicular pattern and reduced hepatocyte injury: CK18 and ubiquitin immunoreactivity were decreased in MCD + VANC vs. MCD, and hepatic IL-8 and TGF-β1 levels were lower in MCD + VANC vs. STD. Taxonomically, STD mice had Lactobacillus-rich microbiota. The MCD diet alone reduced alpha diversity (α-diversity), modestly lowered Firmicutes and increased Desulfobacterota/Fusobacteriota. Vancomycin alone caused a much larger collapse in richness, depleting Gram-positive commensals and promoting blooms of Escherichia–Shigella, Klebsiella, Parabacteroides, and Akkermansia. In the MCD + VANC group, vancomycin profoundly remodeled the microbiota, eliminating key commensals (e.g., Lactobacillus) and enriching Desulfobacterota, Fusobacteriota, and Campylobacterota. Oral vancomycin in the MCD model of NASH improved liver injury markers and altered steatosis morphology, but concurrently reprogrammed the gut into a low-diversity, pathobiont-enriched ecosystem with near-loss of Lactobacillus. These findings highlight a therapeutic trade-off—hepatic benefit accompanied by microbiome cost—that should guide microbiota-targeted strategies for NAFLD/NASH. Full article

Objective: Tuo-Min-Ding-Chuan decoction (TMDC), a traditional Chinese prescription, has demonstrated significant clinical efficacy in treating allergic asthma. This study aimed to investigate the mechanism of TMDC in treating asthma from the perspective of Treg cells and gut microbiota across distinct gut segments (jejunum, ileum, cecum, and colon). Methods: An ovalbumin (OVA)-induced asthma model was established in mice, followed by oral administration of TMDC at high, medium, and low dose. Immune cells and lung inflammation were examined to assess asthma severity. Microbial composition was determined by 16S rRNA sequencing. Antibiotic cocktail and Lactobacillus rhamnosus GG (LGG) were administrated to confirm the key role of specific bacteria. Results: TMDC attenuated lung inflammation (p < 0.01) and eosinophilic infiltration (p < 0.01) as well as IL-4 and IL-5 secretion (p < 0.01); it was also associated with an increase in Treg cells in the lung, small intestine (SI), and colon (p < 0.05). Meanwhile, TMDC restored the number of microbiota species and the Shannon index in the hindgut and reinstated beneficial bacteria, such as Allobaculum and Turicibacter, which were diminished in asthmatic mice. Notably, TMDC significantly enriched Bifidobacterium and Lactobacillus, particularly in the hindgut. Lactobacillus abundance was significantly correlated (p < 0.05) with Treg cells, IL-4, IL-5, and eosinophils. Furthermore, LGG supplementation restored elevated lung inflammation (p < 0.05) and decreased Treg cells (p < 0.01) due to antibiotic-induced microbiota depletion. Conclusion: TMDC alleviated asthma by promoting Treg cell expansion in a Lactobacillus-dependent manner across different gut segments, providing new insights into its therapeutic mechanisms. Full article

Ulcerative colitis (UC) is characterized clinically by intestinal inflammation and gut microbiota dysbiosis. The consumption of biologics, although effective in inflammation control, may lead to adverse effects and is inconvenient for at-home administration. Goat milk-derived extracellular vesicles (GMEVs) have been proposed as a supplement to prevent intestinal inflammation. However, their therapeutic potential for colitis remains elusive. This study aimed to explore the preventive effect of GMEVs on colitis and its underlying mechanisms through the microbiota-immune axis using a dextran sodium sulfate (DSS)-induced colitis mouse model. We found that a pre-treatment of 20 mg/kg/d GMEVs effectively prevented body weight loss, colon shortening, the depletion of colonic goblet cells, and the disappearance of crypts, while enhancing the intestinal mucosal barrier. Consistent with these phenotypes, GMEV pre-treatment increased levels of IL-22 and IL-10 and decreased levels of IL-1β, TNF-α, IL-6, and iNOS. However, GMEVs themselves had no effect on normal mice. Paralleling the alleviation of intestinal inflammation, GMEV pre-treatment also restored the reduction in unclassified Muribaculaceae, Dubosiella, and Lactobacillus and suppressed the expansion of Alistipes and Proteobacteria following DSS treatment. Additionally, GMEV intake significantly downregulated the expression of proteins in the NF-κB signaling pathway induced by DSS. In summary, GMEVs could prevent colitis by regulating intestinal inflammation, the intestinal mucosal barrier, gut microbiota, organ damage, and the immune microenvironment. This study demonstrated that GMEVs have potential application prospects for UC prevention. Full article

Crohn’s and ulcerative colitis are common conditions associated with inflammatory bowel disease as well as intestinal flora and epithelial barrier dysfunction. A novel fermented Lactobacillus brevis (AL0035) herein assayed in a trinitro benzene sulfonic acid (TNBS)-induced colitis mice model after oral administration significantly counteracted the body weight loss and improves the disease activity index and histological injury scores. AL0035 significantly decreased the mRNA and protein expression of different pro-inflammatory cytokines (TNFalpha, IL-1beta, IL-6, IL-12, IFN-gamma) and enhanced the expression of IL-10. In addition, the probiotic promoted the expression of tight junction proteins, such as ZO-1, keeping the intestinal mucosal barrier function to attenuate colitis symptoms in mice. Markers of inflammation cascade such as myeloperoxidase (MPO) and PPAR-gamma measured in the colon were also modified by AL0035 treatment. AL0035 was also able to reduce different lymphocyte markers’ infiltration in the colon (GATA-3, T-Bet, NK1.1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), a key chemokine involved in the migration and infiltration of monocytes/macrophages in the immunological surveillance of tissues and inflammation. In colonic microbiota profile analysis through 16S rRNA sequencing, AL0035 increased the microbial diversity depleted by TNBS administration and the relative abundance of the Lactobacillaceae and Lachnospiraceae families, whereas it decreased the abundance of Proteobacteria. Altogether, these data indicated that AL0035 could lower the severity of colitis induced by TNBS by regulating inflammatory cytokines, increasing the expression of tight junction proteins and modulating intestinal microbiota, thus preventing tissue damage induced by colitis. Full article

Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses. Full article

The ketogenic diet (KD) has emerged as a popular weight-loss regimen in recent years. However, it has been confirmed to elicit a mild inflammatory response in the intestinal epithelium and exacerbate various digestive disorders. The severity of acute pancreatitis (AP) is closely associated with the permeability of the intestinal epithelium and gut microbiota, yet the impact of KD on acute pancreatitis remains unclear. In this study, we induced acute pancreatitis using L-arginine in mice fed with KD. The consumption of KD resulted in an elevation of lipopolysaccharide-binding protein (LBP), accompanied by upregulated cytokines (IL-1a, IL-5, IL-12, MIP-1a, and Rantes) and dysfunction of the intestinal barrier both in control and AP groups. The bloom of Lachnospirales and Erysipelotrichales was observed as a specific profile of gut microbiota in KD-fed mice with AP, along with downregulation of carbohydrate metabolism and depletion of short-chain fatty acids (SCFAs). Antibiotic decontamination reduced the cytokine storm and tissue necrosis but did not significantly improve the integrity of the intestinal barrier in KD-fed mice with AP. The overgrowth of Mycoplasmatales in feces and Enterobacterales in colonic tissue appears to explain the limitation of antibiotic treatment to aggravate acute pancreatitis. Butyrate supplementation attenuated the depletion of SCFAs, promoted the intestinal barrier, and reduced the necrotic area in AP mice. The bloom of Bacteroidales and the correlated increase in tryptophan metabolism explain the therapeutic potential of butyrate supplements for acute pancreatitis. In conclusion, our findings suggest that the ketogenic diet exacerbates acute pancreatitis through its impact on the gut microbiota and subsequent disruption of the intestinal barrier, while butyrate supplementation reverses this effect. Full article

Human food-borne infections with the enteropathogen Campylobacter jejuni are becoming increasingly prevalent worldwide. Since antibiotics are usually not indicated in campylobacteriosis, alternative treatment regimens are important. We here investigated potential disease-alleviating effects of menthol and of extracts from tormentil, raspberry leaves, and loosestrife in acute murine campylobacteriosis. Therefore, C. jejuni-infected microbiota-depleted IL-10^−/− mice were orally treated with the compounds alone or all in combination from day 2 until day 6 post-infection. Whereas neither treatment regimen affected gastrointestinal pathogen loads, the combination of compounds alleviated C. jejuni-induced diarrheal symptoms in diseased mice on day 6 post-infection. Furthermore, the therapeutic application of tormentil and menthol alone and the combination of the four compounds resulted in lower colonic T cell numbers in infected mice when compared to placebo counterparts. Notably, pro-inflammatory cytokines measured in mesenteric lymph nodes taken from C. jejuni-infected mice following tormentil, menthol, and combination treatment did not differ from basal concentrations. However, neither treatment regimen could dampen extra-intestinal immune responses, including systemic pro-inflammatory cytokine secretion on day 6 post-infection. In conclusion, the combination of menthol and of extracts from tormentil, raspberry leaves, and loosestrife constitutes an antibiotic-independent approach to alleviate campylobacteriosis symptoms. Full article

The progressively rising food-borne Campylobacter jejuni infections pose serious health problems and socioeconomic burdens. Given that antibiotic therapy is not recommended for most campylobacteriosis patients, novel treatment options include strategies targeting iron homeostasis that impacts both C. jejuni virulence and inflammatory cell damage caused by toxic oxygen species. In our preclinical intervention study, we tested potential disease-alleviating effects upon prophylactic oral application of the iron-chelating compound desferoxamine (DESF) in acute murine campylobacteriosis. Therefore, microbiota-depleted IL-10^−/− mice received synthetic DESF via the drinking water starting seven days before oral infection with C. jejuni strain 81-176. Results revealed that the DESF application did not reduce gastrointestinal pathogen loads but significantly improved the clinical outcome of infected mice at day 6 post-infection. This was accompanied by less pronounced colonic epithelial cell apoptosis, attenuated accumulation of neutrophils in the infected large intestines and abolished intestinal IFN-γ and even systemic MCP-1 secretion. In conclusion, our study highlights the applied murine campylobacteriosis model as suitable for investigating the role of iron in C. jejuni infection in vivo as demonstrated by the disease-alleviating effects of specific iron binding by oral DESF application in acute C. jejuni induced enterocolitis. Full article

Given that human Campylobacter jejuni infections are rising globally and antibiotic treatment is not recommended, infected patients would substantially benefit from alternative therapeutic strategies. Short-chain fatty acids such as butyrate are known for their health benefits, including anti-microbial and anti-inflammatory effects. This prompted us to investigate potential disease-alleviating properties of butyrate treatment during acute murine C. jejuni-induced enterocolitis. Therefore, following gut microbiota depletion IL-10^−/− mice were challenged with 10⁹ viable C. jejuni cells by oral gavage and treated with butyrate via the drinking water (22 g/L) starting on day 2 post-infection. As early as day 3 post-infection, butyrate reduced diarrheal severity and frequency in treated mice, whereas on day 6 post-infection, gastrointestinal C. jejuni burdens and the overall clinical outcomes were comparable in butyrate- and placebo-treated cohorts. Most importantly, butyrate treatment dampened intestinal pro-inflammatory immune responses given lower colonic numbers of apoptotic cells and neutrophils, less distinct TNF-α secretion in mesenteric lymph nodes and lower IL-6 and MCP-1 concentrations in the ileum. In conclusion, results of our preclinical intervention study provide evidence that butyrate represents a promising candidate molecule for the treatment of acute campylobacteriosis. Full article

Human noroviruses (HuNoVs) are the main cause of acute gastroenteritis causing more than 50,000 deaths per year. Recent evidence shows that the gut microbiota plays a key role in enteric virus infectivity. In this context, we tested whether microbiota depletion or microbiota replacement with that of human individuals susceptible to HuNoVs infection could favor viral replication in mice. Four groups of mice (n = 5) were used, including a control group and three groups that were treated with antibiotics to eliminate the autochthonous intestinal microbiota. Two of the antibiotic-treated groups received fecal microbiota transplantation from a pool of feces from infants (age 1–3 months) or an auto-transplantation with mouse feces that obtained prior antibiotic treatment. The inoculation of the different mouse groups with a HuNoVs strain (GII.4 Sydney [P16] genotype) showed that the virus replicated more efficiently in animals only treated with antibiotics but not subject to microbiota transplantation. Viral replication in animals receiving fecal microbiota from newborn infants was intermediate, whereas virus excretion in feces from auto-transplanted mice was as low as in the control mice. The analysis of the fecal microbiota by 16S rDNA NGS showed deep variations in the composition in the different mice groups. Furthermore, differences were observed in the gene expression of relevant immunological mediators, such as IL4, CXCL15, IL13, TNFα and TLR2, at the small intestine. Our results suggest that microbiota depletion eliminates bacteria that restrict HuNoVs infectivity and that the mechanism(s) could involve immune mediators. Full article

Intestinal microbiota-virus-host interaction has emerged as a key factor in mediating enteric virus pathogenicity. With the aim of analyzing whether human gut bacteria improve the inefficient replication of human rotavirus in mice, we performed fecal microbiota transplant (FMT) with healthy infants as donors in antibiotic-treated mice. We showed that a simple antibiotic treatment, irrespective of FMT, resulted in viral shedding for 6 days after challenge with the human rotavirus G1P[8] genotype Wa strain (RVwa). Rotavirus titers in feces were also significantly higher in antibiotic-treated animals with or without FMT but they were decreased in animals subject to self-FMT, where a partial re-establishment of specific bacterial taxons was evidenced. Microbial composition analysis revealed profound changes in the intestinal microbiota of antibiotic-treated animals, whereas some bacterial groups, including members of Lactobacillus, Bilophila, Mucispirillum, and Oscillospira, recovered after self-FMT. In antibiotic-treated and FMT animals where the virus replicated more efficiently, differences were observed in gene expression of immune mediators, such as IL1β and CXCL15, as well as in the fucosyltransferase FUT2, responsible for H-type antigen synthesis in the small intestine. Collectively, our results suggest that antibiotic-induced microbiota depletion eradicates the microbial taxa that restrict human rotavirus infectivity in mice. Full article

The microbiota of the gut–lung axis affects local and far-reaching immune responses and might also trigger chronic and inflammatory diseases. We hypothesized that gut dysbiosis induced by obesity, which coexists in countries with a high tuberculosis burden, aggravates the host susceptibility and the pulmonary damage tolerance. To assess our hypothesis, we used a model of high-fat diet (HFD)-induced obesity, followed by infection of C57BL/6 mice with Mycobacterium tuberculosis. We showed that obesity increased the susceptibility, the pulmonary inflammation and IFN-γ levels in M. tuberculosis-infected mice. During the comorbidity obesity and tuberculosis, there is an increase of Bacteroidetes and Firmicutes in the lungs, and an increase of Firmicutes and butyrate in the feces. Depletion of gut microbiota by antibiotic treatment in the obese infected mice reduced the frequencies of CD4⁺IFN-γ⁺IL-17⁻ cells and IFN-γ levels in the lungs, associated with an increase of Lactobacillus. Our findings reinforce the role of the gut–lung axis in chronic infections and suggest that the gut microbiota modulation may be a potential host-directed therapy as an adjuvant to treat TB in the context of IFN-γ-mediated immunopathology. Full article

Foodborne Campylobacter jejuni infections are on the rise and responsible for worldwide serious health issues. Increasing resistance of C. jejuni strains against antimicrobial treatments, necessitates antibiotics-independent treatment options for acute campylobacteriosis. Activated charcoal (AC) constitutes a long-known and safe compound for the treatment of bacterial enteritis. In this preclinical intervention study, we addressed potential anti-pathogenic and immune-modulatory effects of AC during acute experimental campylobacteriosis. Therefore, microbiota-depleted IL-10^−/− mice were infected with C. jejuni by gavage and challenged with either AC or placebo via the drinking water starting on day 2 post-infection. On day 6 post-infection, AC as compared to placebo-treated mice did not only harbor lower intestinal pathogen loads but also presented with alleviated C. jejuni-induced clinical signs such as diarrhea and wasting symptoms. The improved clinical outcome of AC-treated mice was accompanied by less colonic epithelial cell apoptosis and reduced pro-inflammatory immune responses in the intestinal tract. Notably, AC treatment did not only alleviate intestinal, but also extra-intestinal and systemic immune responses as indicated by dampened pro-inflammatory mediator secretion. Given the anti-pathogenic and immune-modulatory properties of AC in this study, a short-term application of this non-toxic drug constitutes a promising antibiotics-independent option for the treatment of human campylobacteriosis. Full article

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard^®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard^® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10^−/− mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard^® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard^® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard^® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans. Full article