Background: Alteration of the gut microbiota may contribute to the development of inflammatory bowel disease (IBD). Epigallocatechin-3-gallate (EGCG), a major bioactive constituent of green tea, is known to be beneficial in IBD alleviation. However, it is unclear whether the gut microbiota exerts an effect when EGCG attenuates IBD. Results: We first explored the effect of oral or rectal EGCG delivery on the DSS-induced murine colitis. Our results revealed that anti-inflammatory effect and colonic barrier integrity were enhanced by oral, but not rectal, EGCG. We observed a distinct EGCG-mediated alteration in the gut microbiome by increasing Akkermansia abundance and butyrate production. Next, we demonstrated that the EGCG pre-supplementation induced similar beneficial outcomes to oral EGCG administration. Prophylactic EGCG attenuated colitis and significantly enriched short-chain fatty acids (SCFAs)-producing bacteria such as Akkermansia and SCFAs production in DSS-induced mice. To validate these discoveries, we performed fecal microbiota transplantation (FMT) and sterile fecal filtrate (SFF) to inoculate DSS-treated mice. Microbiota from EGCG-dosed mice alleviated the colitis over microbiota from control mice and SFF shown by superiorly anti-inflammatory effect and colonic barrier integrity, and also enriched bacteria such as Akkermansia and SCFAs. Collectively, the attenuation of colitis by oral EGCG suggests an intimate involvement of SCFAs-producing bacteria Akkermansia, and SCFAs, which was further demonstrated by prophylaxis and FMT. Conclusions: This study provides the first data indicating that oral EGCG ameliorated the colonic inflammation in a gut microbiota-dependent manner. Our findings provide novel insights into EGCG-mediated remission of IBD and EGCG as a potential modulator for gut microbiota to prevent and treat IBD.

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders.

: Background: The microbiota presents a compartmentalized distribution across different gut segments. Hence, the exogenous microbiota from a particular gut segment might only invade its homologous gut location during microbiota transplantation. Feces as the excreted residue contain most of the large-intestinal microbes but lack small-intestinal microbes. We speculated that whole-intestinal microbiota transplantation (WIMT), comprising jejunal, ileal, cecal, and colonic microbiota, would be more effective for reshaping the entire intestinal microbiota than conventional fecal microbiota transplantation fecal microbiota transplantation (FMT).Results: We modeled the compartmentalized colonization of the gut microbiota via transplanting the microbiota from jejunum, ileum, cecum, and colon, respectively, into the germ-free mice. Transplanting jejunal or ileal microbiota induced more exogenous microbes’ colonization in the small intestine (SI) of germ-free mice rather than the large intestine (LI), primarily containing Proteobacteria, Lactobacillaceae, and Cyanobacteria. Conversely, more saccharolytic anaerobes from exogenous cecal or colonic microbiota, such as Bacteroidetes, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae, established in the LI of germ-free mice that received corresponding intestinal segmented microbiota transplantation. Consistent compartmentalized colonization patterns of microbial functions in the intestine of germ-free mice were also observed. Genes related to nucleotide metabolism, genetic information processing, and replication and repair were primarily enriched in small-intestinal communities, whereas genes associated with the metabolism of essential nutrients such as carbohydrates, amino acids, cofactors, and vitamins were mainly enriched in large-intestinal communities of germ-free mice. Subsequently, we compared the difference in reshaping the community structure of germ-free mice between FMT and WIMT. FMT mainly transferred LI-derived microorganisms and gene functions into the recipient intestine with sparse SI-derived microbes successfully transplanted. However, WIMT introduced more SI-derived microbes and associated microbial functions to the recipient intestine than FMT. Besides, WIMT also improved intestinal morphological development as well as reduced systematic inflammation responses of recipients compared with FMT.Conclusions: Segmented exogenous microbiota transplantation proved the spatial heterogeneity of bacterial colonization along the gastrointestinal tract, i.e., the microbiota from one specific location selectively colonizes its homologous gut region. Given the lack of exogenous small-intestinal microbes during FMT, WIMT may be a promising alternative for conventional FMT to reconstitute the microbiota across the entire intestinal tract.

Dietary phenolic acids alleviate intestinal inflammation through altering gut microbiota composition and regulating macrophage activation. However, it is unclear how individual phenolic acids affect the interactions between intestinal microbiota and macrophages in the context of inflammatory bowel disease (IBD). Here, we aim to elucidate the mechanism by which phenolic acids alleviate gut inflammation. Mice with or without depletion of macrophages were administered with four individual phenolic acids including chlorogenic, ferulic, caffeic, and ellagic acids, following dextran sulfate sodium (DSS) treatment. Gut microbiota depletion and fecal microbiota transplantation were further performed in mice to investigate the role of the gut microbiota in phenolic acid-mediated protective effect. Colitis severity was evaluated using histological, serological, and immunological measurements. Absence of intestinal microbiota and macrophage deteriorate the epithelial injury in DSS colitis. Chlorogenic acid mitigated colitis by reducing M1 macrophage polarization through suppression of pyruvate kinase M 2 (Pkm2)-dependent glycolysis and inhibition of NOD-like receptor protein 3 (Nlrp3) activation. However, ferulic acid-mediated reduction of colitis was neutrophil-dependent through diminishing the formation of neutrophil extracellular traps. On the other hand, the beneficial effects of caffeic acid and ellagic acid were dependent upon the gut microbiota. In fact, urolithin A (UroA), a metabolite transformed from ellagic acid by the gut microbiota, was found to alleviate colitis and enhance gut barrier function in an IL22-dependent manner. Overall, our findings demonstrated that the mechanisms by which phenolic acid protected against colitis were resulted from the interaction between gut microbiota and macrophage-neutrophil.

Prophage activation in intestinal environments has been frequently reported to affect host adaptability, pathogen virulence, gut bacterial community composition, and intestinal health. Prophage activation is mostly caused by various stimulators, such as diet, antibiotics, some bacterial metabolites, gastrointestinal transit, inflammatory environment, oxidative stress, and quorum sensing. Moreover, with advancements in biotechnology and the deepening cognition of prophages, prophage activation regulation therapy is currently applied to the treatment of some bacterial intestinal diseases such as Shiga toxin-producing Escherichia coli infection. This review aims to make headway on prophage induction in the intestine, in order to make a better understanding of dynamic changes of prophages, effects of prophage activation on physiological characteristics of bacteria and intestinal health, and subsequently provide guidance on prophage activation regulation therapy.

The aim of this study was to investigate the effects of the high level of xylooligosaccharides (XOS) on growth performance, antioxidant capability, immune function, and fecal microbiota in weaning piglets. The results showed that 28 d body weight exhibited linear and quadratic increases (P < 0.05) with increasing dietary XOS level, as well as average daily feed intake (ADFI) on d 15–28, average daily gain (ADG) on d 15–28 and 1–28. There was a linear decrease (P < 0.05) between XOS levels and feed conversion rate (FCR) on d 1–14 and 1–28. Additionally, glutathione peroxidase (GSH-Px) showed a linear increase (P < 0.05), while the malondialdehyde (MDA) level decreased linearly and quadratically (P < 0.05) with the increasing dietary level of XOS. Moreover, the XOS treatments markedly increased the levels of immunoglobulin A (Ig A) (linear, P < 0.05; quadratic, P < 0.05), IgM (quadratic, P < 0.05), IgG (linear, P < 0.05), and anti-inflammatory cytokine interleukin-10 (IL-10) (quadratic, P < 0.05) in serum, while the IL-1β (linear, P < 0.05; quadratic, P < 0.05) and IL-6 (linear, P < 0.05) decreased with increasing level of XOS. Microbiota analysis showed that dietary supplementation with 1.5% XOS decreased (P < 0.05) the α-diversity and enriched (P < 0.05) beneficial bacteria including Lactobacillus, Bifidobacterium, and Fusicatenibacter at the genus level, compared with the control group. Importantly, linearly increasing responses (P < 0.05) to fecal acetate, propionate, butyrate, and total short-chain fatty acids (SCFAs) were observed with increasing level of XOS. Spearman correlation analyses found that Lactobacillus abundance was positively correlated with ADG, acetate, propionate, and IgA (P < 0.05), but negatively correlated with IL-1β (P < 0.05). Bifidobacterium abundance was positively related with ADFI, total SCFAs, IgG, and IL-10 (P < 0.05), as well as g_Fusicatenibacter abundance with ADFI, total SCFAs, and IL-10. However, Bifidobacterium and Fusicatenibacter abundances were negatively associated with MDA levels (P < 0.05). In summary, dietary supplementation with XOS can improve the growth performance in weaning piglets by increasing antioxidant capability, enhancing immune function, and promoting beneficial bacteria counts.