Meta-analysis reveals Helicobacter pylori mutual exclusivity and reproducible gastric microbiome alterations during gastric carcinoma progression.

Accumulating evidence shows that the gastric bacterial community may contribute to the development of gastric cancer (GC). However, the reported alterations of gastric microbiota were not always consistent among the literature. To assess reproducible signals in gastric microbiota during the progression of GC across studies, we performed a meta-analysis of nine publicly available 16S datasets with standard tools of the state-of-the-art. Despite study-specific batch effect, significant changes in the composition of the gastric microbiome were found during the progression of gastric carcinogenesis, especially when the Helicobacter pylori (HP) reads were removed from analyses to mitigate its compositional effect as they accounted for extremely large proportions of sequencing depths in many gastric samples. Differential microbes, including Fusobacterium, Leptotrichia, and several lactic acid bacteria such as Bifidobacterium, Lactobacillus, and Streptococcus anginosus, which were frequently and significantly enriched in GC patients compared with gastritis across studies, had good discriminatory capacity to distinguish GC samples from gastritis. Oral microbes were significantly enriched in GC compared to precancerous stages. Intriguingly, we observed mutual exclusivity of different HP species across studies. In addition, the comparison between gastric fluid and mucosal microbiome suggested their convergent dysbiosis during gastric disease progression. Taken together, our systematic analysis identified novel and consistent microbial patterns in gastric carcinogenesis.

Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis.

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. Video Abstract.