Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host

Wexler, Aaron G.; Guiberson, Emma R.; Beavers, William N.; Shupe, John; Washington, Mary Kay; Lacy, D. Borden; Caprioli, Richard M.; Spraggins, Jeffrey M.; Skaar, Eric P.

doi:10.1016/j.celrep.2021.109683

Cited by 21 publications

(22 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, BAs are important regulators in the life history of Clostridium difficile . For example, the spore germination and outgrowth of Clostridium difficile are promoted by TCA (primary BA) but inhibited by DCA (secondary BA) ( Silverman et al., 2017 ; Abbas and Zackular, 2020 ; Theriot and Petri, 2020 ; Wexler et al., 2021 ). These findings were also supported by the correlation analysis of gut microbiota and BAs in this study.…”

Section: Discussionmentioning

confidence: 99%

Total glycosides contribute to the anti-diarrheal effects of Qiwei Baizhu Powder via regulating gut microbiota and bile acids

Xie

Deng

Zheng

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Qiwei Baizhu Powder (QWBZP) is a traditional Chinese medicine formula for treating diarrhea induced by various causes. It elicits an anti-diarrheal effect by regulating the gut microbiota (diversity, structure, and abundance). However, the contribution of different components in the QWBZP decoction to this effect remains unclear. In this study, we used the QWBZP decoction as a reference standard to investigate the effects of total glycosides (TGs) extracted from QWBZP decoction on the gut microbiota and bile acid metabolism in mice with antibiotic-associated diarrhea (AAD). The results of 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) analysis showed that the effect of total glycosides of Qiwei Baizhu Powder (QWBZP-TG) on specific intestinal bacteria and bile acids was similar to that of the QWBZP decoction, but the intensity of this effect was more significant in the case of QWBZP-TG. The QWBZP decoction and QWBZP-TG promoted the proliferation of Lactobacillus and inhibited the growth of Proteus, Clostridium, Eubacterium, Facklamia, and Escherichia in AAD mice. They also increased the levels of deoxycholic acid and beta-muricholic acid and decreased those of taurocholate acid, tauro-alpha-muricholic acid, and tauro-beta-muricholic acid in AAD mice. Lactobacillus was the key bacterial genus responding to QWBZP-TG. Thus, this study provides novel insights into the bioactive components of QWBZP and their contribution to its effects.

show abstract

Section: Discussionmentioning

confidence: 99%

Total glycosides contribute to the anti-diarrheal effects of Qiwei Baizhu Powder via regulating gut microbiota and bile acids

Xie

Deng

Zheng

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

show abstract

“…The generated DCA signals back to C. difficile to initiate biofilm production and maintenance in the host (Figure 8). Moreover, C. difficile could take advantage of high TA levels during the initial stages of infection not only for germination (63), but for generation of CA that can be used by other bacteria that do not encode BSH enzymes to generate DCA and persist in the gut environment and, potentially, to cause recurring infections.…”

Section: Discussionmentioning

confidence: 99%

“…C. difficile could take advantage of high TA levels during the initial stages of infection not only for germination(63), but for generation of CA that can be used by other bacteria that do not encode BSH enzymes to generate DCA and persist in the gut environment and, potentially, to cause recurring infections. by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

mentioning

confidence: 99%

Clostridioides difficile bile salt hydrolase activity has substrate specificity and affects biofilm formation

Aguirre

Sorg

2022

Preprint

View full text Add to dashboard Cite

The Clostridioides difficile pathogen is responsible for nosocomial infections. Germination is an essential step for the establishment of C. difficile infection (CDI) because toxins that are secreted by vegetative cells are responsible for the symptoms of CDI. Germination can be stimulated by the combinatorial actions of certain amino acids and either conjugated or deconjugated cholic acid-derived bile salts. During synthesis in the liver, cholic acid- and chenodeoxycholic acid-class bile salts are conjugated with either taurine or glycine at the C24 carboxyl. During GI transit, these conjugated bile salts are deconjugated by microbes that express bile salt hydrolases (BSHs). Here, we surprisingly find that several C. difficile strains have BSH activity. We observed this activity in both C. difficile vegetative cells and in spores and that the observed BSH activity was specific to taurine-derived bile salts. Additionally, we find that this BSH activity can produce cholate for metabolic conversion to deoxycholate by C. scindens. The C. scindens-produced deoxycholate signals to C. difficile to initiate biofilm formation. Our results show that C. difficile BSH activity has the potential to influence the interactions between microbes and this could extend to the GI setting.ImportanceBoth primary and secondary bile salts are well-established to impact C. difficile spore germination and vegetative growth. Here, we find that C. difficile vegetative cells, and spores, have bile salt hydrolase activity that is specific to taurine-derived bile salts. When grown in co-culture with the secondary bile salt-producing bacterium, C. scindens, we find that C. difficile-mediated deconjugation of taurocholate, ‘feeds’ C. scindens cholate. C. scindens 7α-dehydroxylates cholate to deoxycholate. The C. scindens-produced deoxycholate then stimulates biofilm formation by C. difficile cells. Thus, this suggests that the bile salt hydrolase activity expressed by several C. difficile strains could be responsible for modulating in vivo biofilm formation and maintenance in a host.

show abstract

“…Regardless, C. difficile encounters bile acid during colonization and its growth in the gut may impact bile acid synthesis in the liver. Taking advantage of MALDI imaging mass spectrometry, Wexler et al 51 found the levels of primary bile acids in the mouse gut increased significantly as early as one-day post-CDI. Additionally, the authors found that the introduction of cholestyramine, a bile-acid sequestering drug, lead to delayed C. difficile colonization.…”

Section: Bile Acid Metabolites and Their Role In C Difficil...mentioning

confidence: 99%

“…Additionally, the authors found that the introduction of cholestyramine, a bile-acid sequestering drug, lead to delayed C. difficile colonization. 51 Their results suggest that primary bile acids are required to efficiently establish C. difficile in a host.…”

Section: Bile Acid Metabolites and Their Role In C Difficil...mentioning

confidence: 99%

Gut associated metabolites and their roles in Clostridioides difficile pathogenesis

Aguirre

Sorg

2022

Gut Microbes

View full text Add to dashboard Cite

The nosocomial pathogen Clostridioides difficile is a burden to the healthcare system. Gut microbiome disruption, most commonly by broad-spectrum antibiotic treatment, is well established to generate a state that is susceptible to CDI. A variety of metabolites produced by the host and/or gut microbiota have been shown to interact with C. difficile . Certain bile acids promote/inhibit germination while other cholesterol-derived compounds and amino acids used in the Stickland metabolic pathway affect growth and CDI colonization. Short chain fatty acids maintain intestinal barrier integrity and a myriad of other metabolic compounds are used as nutritional sources or used by C. difficile to inhibit or outcompete other bacteria in the gut. As the move toward non-antibiotic CDI treatment takes place, a deeper understanding of interactions between C. difficile and the host’s gut microbiome and metabolites becomes more relevant.

show abstract

Clostridioides difficile infection induces a rapid influx of bile acids into the gut during colonization of the host

Cited by 21 publications

References 43 publications

Total glycosides contribute to the anti-diarrheal effects of Qiwei Baizhu Powder via regulating gut microbiota and bile acids

Total glycosides contribute to the anti-diarrheal effects of Qiwei Baizhu Powder via regulating gut microbiota and bile acids

Clostridioides difficile bile salt hydrolase activity has substrate specificity and affects biofilm formation

Gut associated metabolites and their roles in Clostridioides difficile pathogenesis

Contact Info

Product

Resources

About