Wenfei Qin’s research while affiliated with Shanghai Jiao Tong University and other places

The role of mast cells (MCs) in ulcerative colitis (UC) development is controversial. FcεRI, the IgE high-affinity receptor, is known to activate MCs. However, its role in UC remains unclear. In our study, Anti-FcεRI showed highly diagnostic value for UC. FcεRIα knockout in mice ameliorated DSS-induced colitis in a gut microbiota-dependent manner. Increased Lactobacillus abundance in FcεRIα deficient mice showed strongly correlation with the remission of colitis. RNA sequencing indicated activation of the NLRP6 inflammasome pathway in FcεRIα knockout mice. Additionally, Lactobacillus plantarum supplementation protected against inflammatory injury and goblet cell loss, with activation of the NLRP6 inflammasome during colitis. Notably, this effect was absent when the strain is unable to produce lactic acid. In summary, colitis was mitigated in FcεRIα deficient mice, which may be attributed to the increased abundance of Lactobacillus. These findings contribute to a better understanding of the relationship between allergic reactions, microbiota, and colitis.

Lactiplantibacillus plantarum is selective for carbohydrate utilization, which is primarily regulated by the catabolic control protein A (ccpA). To investigate the impact of carbohydrate metabolism on the in vivo colonization of L. plantarum AR113, we constructed a ccpA knockout strain (AR113ΔccpA). In vitro assays showed that AR113ΔccpA had a 0.34 decrease in maximum biomass, and a 2.63 h increase in hysteresis time compared to AR113. In a single administration, there was no significant difference in the number of AR113 and AR113ΔccpA in the mucus layers, and the number of AR113 was approximately 34‐times higher than AR113ΔccpA at 48 h in the intestinal lumen. Notably, the knockout of the ccpA gene did not affect the colonization time of AR113 in the intestine during continuous administration. Therefore, the present work demonstrated that the ccpA did not play a crucial role in the in vivo colonization time of AR113 and provided valuable insights into the role of carbohydrate metabolism in bacterial colonization time in vivo.

Fecal microbiota transplantation (FMT) is a promising therapy for inflammatory bowel disease (IBD) via rectifying gut microbiota. The aim of this study was to identify a mechanism of how specific bacteria-associated immune response contributes to alleviated colitis. Forty donors were divided into high (donor H) and low (donor L) groups according to the diversity and the abundance of Bacteroides and Faecalibacterium by 16S rRNA sequencing. FMT was performed on dextran sulfate sodium (DSS)-induced colitis in mice. Mice with colitis showed significant improvement in intestinal injury and immune imbalance after FMT with group donor H (P < 0.05). Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii were identified as targeted strains in donor feces by real-time PCR and droplet digital PCR. Mice with colitis were treated with mono- or dual-bacterial gavage therapy. Dual-bacterial therapy significantly ameliorated intestinal injury compared with mono-bacterial therapy (P < 0.05). Dual-bacterial therapy increased the M2/M1 macrophage polarization and improved the Th17/Treg imbalance and elevated IL-10 production by Tregs compared with the DSS group (P < 0.05). Metabolomics showed increased abundance of lecithin in the glycerophospholipid metabolism pathway. In conclusion, B. thetaiotaomicron and F. prausnitzii, as the key bacteria in donor feces, alleviate colitis in mice. The mechanism may involve increasing lecithin and regulating IL-10 production of intestinal Tregs. NEW & NOTEWORTHY We demonstrate that donors with high abundance of Bacteroides and Faecalibacterium ameliorate dextran sulfate sodium (DSS)-induced colitis in mice by fecal microbiota transplantation (FMT). The combination therapy of Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii is superior to mono-bacterial therapy in ameliorating colitis in mice, of which mechanism may involve promoting lecithin and inducing IL-10 production of intestinal Tregs.

Lactiplantibacillus plantarum is an important member of the probiotic family and colonization of the host intestinal is essential for its continued probiotic function. The mechanism of L. plantarum intestinal colonization has not been elucidated until now, an important reason being that the colonization process is influenced by a number of factors. In this study, to confirm the influences of adhesion ability and host intestinal environment on L. plantarum intestinal colonization, knockouts of L. plantarum AR113 mucin genes were constructed using CRISPR/Cas9 gene editing technology, and polyethylene glycol was used to reduce the intestinal flora abundance. The knockout of L. plantarum AR113 mucin genes barely altered the strain’s tolerance to acid and bile salts. Notably, the adhesion number of AR113ΔLp_1431ΔLp_2233ΔLp_2792 to HT-29 cells was reduced from 175 to 114 per 100 cells. Through in vivo colonization experiments, an increase in the fluorescence intensity of AR113 and AR113ΔLp_1431&2233&2792 was detected the day after the mice were fed, while the deletion of Lp_1431, Lp_2233 and Lp_2792 genes reduced the intestinal tract colonization time from 14 to 11 days. Both AR113 and AR113ΔLp_1431ΔLp_2233ΔLp_2792 were reproduced in the intestine by labeling with 5-(6)-carboxyfluorescein diacetate N-succinimidyl ester. The results showed that the change in fluorescence intensity was closely dependent on the number of adhesions. Finally, compared to the control group, the prolonged intestinal colonization time of AR113ΔLp_1431ΔLp_2233ΔLp_2792 increased mice intestinal flora abundance, with distributions in the duodenum, jejunum, ileum and colon. Collectively, both the intestinal environment and the adhesion ability of L. plantarum AR113 affected intestinal colonization, and the host’s intestinal genetic background may be a key factor in the intestinal colonization of L. plantarum.