The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice

Abstract

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.

Perspective on the Modern Interpretation of the Property Theory of Mild-natured and Sweet-flavored Traditional Chinese Medicine via Gut Microbiota Modulation

“…F. lycii could increase B. fragilis to promote the expression of 1,5-anhydroglucitol (1,5-AG) , upregulate the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ Recombinant Kelch Like ECH Associated Protein 1/(Keap1) pathway, downregulate the TGF-β/Smad pathway, inhibit renal fibrosis, and improve inflammation and intestinal injury. [60] CONCLUSION AND PROSPECT This literature review revealed that the gut microbiota may explain the property theory of TCM from a new perspective. At the genus level, Turicibacter, Parabacteroides, Dubosiella, Bifidobacterium, Bacteroides, Lactobacillus, Oscillospira, and Prevotella were upregulated, whereas Parasutterella, Mucispirillum, LachnoClostridium, Escherichia, Enterococcus, Butyricicoccus, Clostridiales, Blautia, Desulfovibrio, and Oscillibacter were downregulated.…”

“…[61] Moreover, Bifidobacterium and Lactobacillus were increased by Dioscoreae Rhizoma , F. lycii , and Poria and were negatively correlated with endotoxin production. [60] Thus, MS-TCMs can suppress endotoxin production by regulating the gut microbiota.…”

Strategies for applying probiotics in the antibiotic management ofClostridioides difficileinfection

“…154 Zhou et al found that Bacteroides fragilis ameliorated renal fibrosis by decreasing LPS and increasing 1,5-AG levels in mice. 155 Hosomi et al administered Blautia wexlerae orally to mice and confirmed that the strain was sufficient to reduce obesity and alleviate type II diabetes. 120 Huber-Ruano et al found that Odoribacter laneus could improve host glucose tolerance and obesity-associated inflammation by depleting succinate in obese mice.…”

Research Highlights

“…Zhou and coworkers 2 examined and established a causative relationship between the gut microbiota Bacteriodes fragilis ( B. fragilis ) and the progression of renal fibrosis. First, in 2 independent cohorts of CKD patients in China, the authors established that fecal B. fragilis correlated negatively with the stage of CKD assessed by serum BUN and creatinine.…”