The Human Gut Microbe Bacteroides thetaiotaomicron Suppresses Toxin Release from Clostridium difficile by Inhibiting Autolysis

Abstract

Disruption of the human gut microbiota by antibiotics can lead to Clostridium difficile (CD)-associated diarrhea. CD overgrowth and elevated CD toxins result in gut inflammation. Herein, we report that a gut symbiont, Bacteroides thetaiotaomicron (BT), suppressed CD toxin production. The suppressive components are present in BT culture supernatant and are both heat- and proteinase K-resistant. Transposon-based mutagenesis indicated that the polysaccharide metabolism of BT is involved in the inhibitory effect. Among the genes identified, we focus on the methylerythritol 4-phosphate pathway gene gcpE, which supplies the isoprenoid backbone to produce the undecaprenyl phosphate lipid carrier that transports oligosaccharides across the membrane. Polysaccharide fractions prepared from the BT culture suppressed CD toxin production in vitro; the inhibitory effect of polysaccharide fractions was reduced in the gcpE mutant (ΔgcpE). The inhibitory effect of BT-derived polysaccharide fraction was abrogated by lysozyme treatment, indicating that cellwall-associated glycans are attributable to the inhibitory effect. BT-derived polysaccharide fraction did not affect CD toxin gene expression or intracellular toxin levels. An autolysis assay showed that CD cell autolysis was suppressed by BT-derived polysaccharide fraction, but the effect was reduced with that of ΔgcpE. These results indicate that cell wall-associated glycans of BT suppress CD toxin release by inhibiting cell autolysis.

Liver Microbiome in Healthy Rats: The Hidden Inhabitants of Hepatocytes

“…Gut bacteria were largely overlooked until they were found to be closely related with various gut or gut-related disorders, such as irritable bowel syndrome [35][36][37], infectious diarrhea [38], ulcerative colitis, colorectal liver diseases, and obesity-related disorders [39,40]. In addition, gut bacteria can be utilized as a medication strategy [41][42][43][44][45], including fecal microbiota transplantation (FMT) [46][47][48][49][50][51]. Gut bacteria recently became an explosive topic, going through roughly three development stages: (1) Feces microbiome.…”

Liver microbiota in healthy rats: the hidden inhabitants of hepatocytes

“…Gut bacteria were largely overlooked until they were found to be closely related with various gut or gutrelated disorders, such as irritable bowel syndrome [36][37][38], infectious diarrhea [39], ulcerative colitis, colorectal cancer, liver diseases, and obesity related disorders [40,41]. In addition, gut bacteria can be utilized as a medication strategy [42][43][44][45][46], including fecal microbiota transplantation (FMT) [47][48][49][50][51][52]. Gut bacteria recently became an explosive topic, going through roughly three development stages: (1) Feces microbiota.…”

The development of live biotherapeutics against Clostridioides difficile infection towards reconstituting gut microbiota

“… 82 The cell-wall associated glycans of B. thetaiotaomicron were shown to suppress the production of the glycosylated toxins of C. difficile in vitro. 83 As a cephalosporinase-producing anaerobe, the pre-colonized B. thetaiotaomicron produced β-lactamase enzymes to inactivate intraintestinal β-Lactam antibiotics during antibiotic treatment, providing protection for commensal recovery and preventing overgrowth of C. difficile in a mouse model. 84 …”