This study indicated thatC. butyricumprovided a prevention effect against colitis mice, which involved protection of the intestinal barrier and positively regulating gut microbiota. Furthermore, we confirmed that the gut microbiota and metabolites that were induced byC. butyricumalso contributed to the attenuation of DSS-induced colitis. Importantly,C. butyricum-derived EVs showed an effective impact in alleviating colitis.

Increasing studies have shown that obesity is the primary cause of cardiovascular diseases, non-alcoholic fatty liver diseases, type 2 diabetes, and a variety of cancers. The dysfunction of gut microbiota was proved to result in obesity. Recent research indicated ANGPTL4 was a key regulator in lipid metabolism and a circulating medium for gut microbiota and fat deposition. The present study was conducted to investigate the alteration of gut microbiota and ANGPTL4 expression in the gastrointestinal tract of mice treated by the high-fat diet. Ten C57BL/6J mice were randomly allocated to two groups and fed with a high-fat diet (HFD) containing 60% fat or a normal-fat diet (Control) containing 10% fat. The segments of ileum and colon were collected for the determination of ANGPTL4 expression by RT-qPCR and immunohistochemical analysis while the ileal and colonic contents were collected for 16S rRNA gene sequencing. The results showed HFD significantly increased mice body weight, epididymal fat weight, perirenal fat weight, liver weight, and the lipid content in the liver (P < 0.05). The relative expression of ANGPTL4 and the ANGPTL4-positive cells in the ileum and colon of mice was significantly increased by HFD treatment. Furthermore, 16S rRNA gene sequencing of the ileal and colonic microbiota suggested that HFD treatment changed the composition of the gut microbiota. The ratio of Firmicutes to Bacteroidetes and the abundance of Allobaculum was significantly higher in the HFD group than in the Control group while the abundance of Adlercreutzia, Bifidobacterium, Prevotellaceae UCG-001, and Ruminococcus was significantly decreased. Interestingly, the abundance of Allobaculum was positively correlated with the expression of ANGPTL4. These findings provide a theoretical foundation for the development of strategies to control the obesity and related diseases by the regulation of ANGPTL4 and gut microbiota.

Diarrheic disease is a common intestinal health problem worldwide, causing great suffering to humans and animals. Precise manipulation strategies based on probiotics to combat diarrheic diseases have not been fully developed. The aim of this study was to investigate the molecular mechanisms by which probiotics manipulate macrophage against diarrheic disease. Metagenome reveals gut microbiome profiles of healthy and diarrheic piglets. Fecal microbial transplantation (FMT) was employed to explore the causal relationship between gut microbes and diarrhea. The protective role of probiotics and their derived extracellular vesicles (EVs) was investigated in ETEC K88-infected mice. Macrophage depletion was performed to assess the role of macrophages in EVs against diarrhea. Execution of in vitro cell co-culture and transcriptome analyses elucidated the molecular mechanisms by which EVs modulate the macrophage and intestinal epithelial barrier. Escherichia coli was enriched in weaned diarrheic piglets, while Lactobacillus johnsonii (L. john) showed a negative correlation with Escherichia coli. The transmission of diarrheic illness symptoms was achieved by transferring fecal microbiota, but not metabolites, from diarrheic pigs to germ-free (GF) mice. L. john's intervention prevented the transmission of disease phenotypes from diarrheic piglets to GF mice. L. john also reduces the gut inflammation induced by ETEC K88. The EVs secreted by L. john demonstrated enhanced efficacy in mitigating the adverse impacts induced by ETEC K88 through the modulation of macrophage phenotype. In vitro experiments have revealed that EVs activate M2 macrophages in a manner that shuts down ERK, thereby inhibiting NLRP3 activation in intestinal epithelial cells. Our results reveal that intestinal microbiota drives the onset of diarrheic disease and that probiotic-derived EVs ameliorate diarrheic disease symptoms by modulating macrophage phenotypes. These findings can enhance the advancement of innovative therapeutic approaches for diarrheic conditions based on probiotic-derived EVs.

Pig gastrointestinal tracts harbor a heterogeneous and dynamic ecosystem populated with trillions of microbes, enhancing the ability of the host to harvest energy from dietary carbohydrates and contributing to host adipogenesis and fatness. However, the microbial community structure and related mechanisms responsible for the differences between the fatty phenotypes and the lean phenotypes of the pigs remained to be comprehensively elucidated. Herein, we first found significant differences in microbial composition and potential functional capacity among different gut locations in Jinhua pigs with distinct fatness phenotypes. Second, we identified that Jinhua pigs with lower fatness exhibited higher levels of short‐chain fatty acids in the colon, highlighting their enhanced carbohydrate fermentation capacity. Third, we explored the differences in expressed carbohydrate‐active enzyme (CAZyme) in pigs, indicating their involvement in modulating fat storage. Notably, Clostridium butyricum might be a representative bacterial species from Jinhua pigs with lower fatness, and a significantly higher percentage of its genome was dedicated to CAZyme glycoside hydrolase family 13 (GH13). Finally, a subsequent mouse intervention study substantiated the beneficial effects of C. butyricum isolated from experimental pigs, suggesting that it may possess characteristics that promote the utilization of carbohydrates and hinder fat accumulation. Remarkably, when Jinhua pigs were administered C. butyricum, similar alterations in the gut microbiome and host fatness traits were observed, further supporting the potential role of C. butyricum in modulating fatness. Taken together, our findings reveal previously overlooked links between C. butyricum and CAZyme function, providing insight into the basic mechanisms that connect gut microbiome functions to host fatness.

Deoxynivalenol (DON) is a common environmental pollutant that poses a serious health risk to humans worldwide. This study was aim to explore whether gut microbiota is involved in DON-induced intestinal toxicity as well as to reveal effect of probiotics derived from gut microbiota in protecting intestinal barrier and to elucidate mechanism. We found that DON caused disturbed gut microbiota, particularly Lactobacillus murinus (L. murinus) deficiency. DON enhanced M1 macrophage polarization and decreased tight junction protein expression. Microbiota transplantation experiments showed that transfer of DON-disrupted microbiota to healthy mice resulted in delivery of DON-induced intestinal toxicity. Besides, DON lost its damaging effect on macrophage and intestinal barrier in antibiotic-treated mice. Further intervention experiments revealed that L. murinus induce macrophage conversion from M1 to M2 phenotype through secreted extracellular vesicles (EVs) to alleviate DON-induced intestinal barrier disruption. Mechanistically, EVs activate TLR2 to promote M2 macrophage polarization and release IL-10, which in turn enhances intestinal barrier function. Upon successful translation of its efficacy into clinical practice, EVs created from L. murinus could be a novel possible treatment strategy for DON-induced gut disease.