Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.

Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning‐induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti‐inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin’s effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin‐treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets’ fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin‐treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin‐shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.

During weaning transition, mammalian newborns suffer severe enteric infections and thus induced gut microbiota dysbiosis, which in turn aggravates enteric disorder. The synthetic dipeptide glycyl-glutamine (GlyGln) has been used as a diet supplement to improve the weaning transition of newborns. However, the effect of dietary GlyGln supplementation on the gut microbiota of piglets with enteric infection remains unclear. Here, weaned piglets received a basal diet or a basal diet supplemented with 0.25% GlyGln for 3 weeks. Five piglets in each group received an intraperitoneal injection of lipopolysaccharide (LPS) (100 μg per kg BW) (LPS and GlyGln + LPS groups) and meanwhile five piglets in a control group received an intraperitoneal injection of saline (Ctrl group). The results showed that dietary GlyGln supplementation improved the LPS induced inflammation response and damage to the ileum morphology by increasing interleukin 10, tight junction proteins, villus height, and the ratio villus height/crypt depth, but decreasing the crypt depth. For the oxidative status, dietary GlyGln supplementation increased the ileal superoxide dismutase and meanwhile reduced the malondialdehyde and nitric oxide synthase activity (NOS) (total NOS and inducible NOS), compared with that in the LPS group. LPS challenge reduced the diversity of gut microbiota and enriched the facultative anaerobic Escherichia coli. The GlyGln restored alpha diversity and the structure of the gut microbiota by enriching obligate anaerobes and short-chain fatty acid (SCFA)-producing bacteria, including Clostridium, Lachnospira, Phascolarctobacterium, Roseburia, Lachnospiraceae, and Synergistetes. GlyGln enriched the gut microbiota function of carbohydrate metabolism and elevated the ileal SCFA concentrations of propionic acid and butyric acid that had been decreased by the LPS challenge. The beneficial effects of dietary GlyGln supplementation are closely associated with its enriched bacteria and SCFAs. Taken together, dietary GlyGln supplementation improved the gut microbiota dysbiosis induced by LPS challenge and enriched obligate anaerobes and SCFA-producing bacteria, which contributed to the amelioration of intestinal integrity, inflammatory responses, and oxidative status.

Intestinal oxidative stress triggers gut microbiota dysbiosis, which is involved in the etiology of post-weaning diarrhea and enteric infections. Ellagic acid (EA) can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis. Therefore, we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage, oxidative stress, and dysbiosis of gut microbiota in weanling piglets. A total of 126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 mL saline orally (Ctrl group), or the basal diet supplemented with 0.1% EA and 2 mL saline orally (EA group), or the basal diet and 2 mL fecal microbiota suspension from the EA group orally (FEA group), respectively, for 14 d. Compared with the Ctrl group, EA group improved growth performance by increasing average daily feed intake and average daily weight gain (P < 0.05) and decreasing fecal scores (P < 0.05). EA group also alleviated intestinal damage by increasing the tight junction protein occludin (P < 0.05), villus height, and villus height-to-crypt depth ratio (P < 0.05), while decreasing intestinal epithelial apoptosis (P < 0.05). Additionally, EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity (P < 0.01), catalase (P < 0.05), and glutathione/oxidized glutathione (P < 0.05), but decreased the oxidative metabolite malondialdehyde (P < 0.05) compared to the Ctrl group. Compared with the Ctrl group, EA and FEA groups increased alpha diversity (P < 0.05), enriched beneficial bacteria (Ruminococcaceae and Clostridium ramosum), and increased metabolites short-chain fatty acids (P < 0.05). Correspondingly, FEA group gained effects comparable to those of EA group on growth performance, intestinal damage, and intestinal antioxidant capacity. In addition, the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices (P < 0.05). Overall, dietary EA supplementation could improve growth performance and attenuate intestinal damage and oxidative stress by regulating the gut microbiota in weanling piglets.

Gut microbiota plays a crucial role in diet nutrient metabolism and maintaining host health. The synthetic dipeptides glycyl-glutamine (Gly-Gln) used as diet supplementation to improve the weaning transition of newborns could be metabolized by certain bacteria in vitro. However, the effect of diet Gly-Gln supplementation on gut microbiota in vivo remains largely unknown. 240 piglets at the age of 28 days (day 28) were randomly assigned to two groups that received a basal diet (Ctrl group) or a basal diet supplemented with 0.25% Gly-Gln (Gly-Gln group) for 3 weeks. Five piglets from each group were euthanized for sampling after overnight fasting on day 38 and day 49, respectively. We determined their structure shifts of the gut microbiota using 16S rDNA-based high-throughput sequencing analysis. Microbial metabolites short-chain fatty acids (SCFAs) in the ileum and the colon were determined with high-performance gas chromatography. The concentrations of endocrine peptides including epidermal growth factor, glucagon-like peptide-1, and glucagon-like peptide-2 in ileal mucosa, as well as the serum concentration of interleukin 1 beta, interleukin 6, interleukin 10, and tumor necrosis factor alpha were determined using Enzyme-Linked Immunosorbent Assay. In addition, we also checked the diarrhea ratio, growth performance, and intestinal morphology to assess the favorable effect of dietary Gly-Gln supplementation during the weaning transition. Dietary Gly-Gln supplementation beneficially altered the gut microbiota by increasing bacterial loading, elevating alpha diversity, and increasing the relative abundance of anaerobes and fiber-degrading bacteria (Phylum Fibrobacteres). Accordingly, the microbial metabolites SCFAs in both colon and ileum, as well as the downstream endocrine peptides in the ileum increased. Meanwhile, dietary Gly-Gln’s favorable weaning transition was reflected in the increase of growth performance indices and the reduced inflammatory response in a time dependent manner. There were significant correlations among the bacteria which responded to dietary Gly-Gln supplementation and these checked indices. Taken together, dietary Gly-Gln supplementation selectively modulated the gut microbiota, which may favor piglets’ weaning-transition. These findings suggest that gut microbiota targeted approaches can be potentially used to improve weaning transition of piglets by dietary functional amino acid.

Cortex Phellodendri extract (CPE) has been used in China to treat diarrhea whereas the underlying mechanisms remain poorly understood. Given that dysbiosis of gut microbiota is a potential reason for diarrhea, and that oral CPE has a low absorption rate in intestine, we hypothesized that modification of gut microbiota is an important factor in CPE's anti-diarrhea effect. To test this hypothesis, we established a diarrhea model by challenging post-weaning mice with oral Enterotoxigenic-Escherichia coli (ETEC), and then the mice were treated with two doses of CPE (80 mg/kg bodyweight and 160 mg/kg bodyweight) or the vehicle control (phosphate buffered saline). Diarrhea indices, inflammatory factors, morphology of jejunum, short-chain fatty acids (SCFAs), and serum endocrine were determined. Modification of gut microbiota was analyzed using 16S rDNA high-throughput sequencing. The changes in functional profiles of gut microbiota were predicted using software PICRUSt. We then explored the association between CPE-responding bacteria and the symptoms indices with the spearman's rank correlation coefficient and significance test. Compared with diarrheal mice, CPE decreased Gut/Carcass ratio and water content of stool, increased goblet cell density and villus height/crypt depth of jejunum, as well as decreased inflammatory indices (Tumour Necrosis Factor-α, Myeloperoxidase and Interleukin-1α). CPE shifted the gut microbiota significantly by increasing alpha diversity (observed species, ace, Shannon, and Simpson) and restoring the gut microbiota. CPE increased Firmicutes and decreased Bacteroidetes. The reduced genus Prevotella, Acinetobacter, and Morganella were positively associated with the diarrhea indices, whereas increased genus Odoribacter, Rikenella, and Roseburia were negatively associated with the diarrhea indices. The abundance of carbohydrate metabolism-related gene and SCFAs-producing bacteria were increased, which was evidenced by increased butyric acid and total SCFAs concentration in the caecum. Consequently, endocrine peptides glucagon-like peptide-1, epidermal growth factor, and peptide tyrosine tyrosine in serum were elevated. CONCLUSIONS: CPE shows a shift function on the gut microbiota in alleviating the diarrhea of mice in a dose-dependent manner. In addition, the microbial metabolites SCFAs may mediate CPE's anti-diarrhea effect by enhancing endocrine secretion in mice.