An elevated deoxycholic acid level induced by high-fat feeding damages intestinal stem cells by reducing the ileal IL-22

Xu, Jingxian; Huang, Dan; Xu, Xiaoquan; Wu, Xiaowan; Liu, Leheng; Niu, Wenlu; Lu, Lungen; Zhou, Hui

doi:10.1016/j.bbrc.2021.09.061

Cited by 14 publications

(11 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous studies have demonstrated that short-term HFD consumption caused increases in faeces and serum bile acids [ 25 , 26 , 27 ] and impaired intestinal barrier function [ 25 ]; however, the exact composition of faecal bile acids is unknown. Therefore, we used bile acid-targeted metabolomics to examine the faecal bile acid composition in mice fed a low-fat diet (LFD) or an HFD.…”

Section: Resultsmentioning

confidence: 99%

“…The HFD induced significant increases in faecal concentrations of unconjugated secondary bile acids, especially cytotoxic DCA. Previous studies have shown that high-fat feeding doubles bile acid levels and that a similar level of bile acid can be achieved by adding 0.2% DCA to the diet [ 9 , 27 , 32 ]. In our study, 0.2% DCA supplementation significantly increased faecal DCA concentrations in mice fed a LFD, while concurrent feeding with CHO reversed the increase in DCA induced by an HFD.…”

Section: Discussionmentioning

confidence: 99%

“…However, excessive bile acids, especially cytotoxic DCA, have been proven to destroy intestinal barrier function [ 7 , 8 , 9 ] and promote colorectal cancer progression by inducing oxidative stress, inhibiting FXR signalling, or activating Wnt and EGFR signalling [ 29 , 35 , 36 , 37 , 38 ]. Several studies have demonstrated that DCA induces the downregulation of intestinal tight junction proteins, such as ZO-1 and occludin, and reduces the number of GCs [ 7 , 8 , 9 , 26 , 27 ]. In addition, our team has confirmed that the DCA-induced dysfunction of PCs leads to gut dysbiosis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Intestinal Stem Cells Damaged by Deoxycholic Acid via AHR Pathway Contributes to Mucosal Barrier Dysfunction in High-Fat Feeding Mice

Liu

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

High-fat exposure leads to impaired intestinal barrier function by disrupting the function of intestinal stem cells (ISCs); however, the exact mechanism of this phenomenon is still not known. We hypothesize that high concentrations of deoxycholic acid (DCA) in response to a high-fat diet (HFD) affect aryl hydrocarbon receptor (AHR) signalling in ISCs and the intestinal barrier. For this purpose, C57BL/6J mice feeding on a low-fat diet (LFD), an HFD, an HFD with the bile acid binder cholestyramine, and a LFD with the DCA were studied. We found that high-fat feeding induced an increase in faecal DCA concentrations. An HFD or DCA diet disrupted the differentiation function of ISCs by downregulating AHR signalling, which resulted in decreased goblet cells (GCs) and MUC2, and these changes were reversed by cholestyramine. In vitro experiments showed that DCA downregulated the differentiation function of ISCs, which was reversed by the AHR agonist 6-formylindolo [3,2-b]carbazole (FICZ). Mechanistically, DCA caused a reduction in indoleamine 2,3-dioxygenase 1 (IDO1) in Paneth cells, resulting in paracrine deficiency of the AHR ligand kynurenine in crypts. We demonstrated for the first time that DCA disrupts intestinal mucosal barrier function by interfering with AHR signalling in ISCs. Supplementation with AHR ligands may be a new therapeutic target for HFD-related impaired intestinal barrier function.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Intestinal Stem Cells Damaged by Deoxycholic Acid via AHR Pathway Contributes to Mucosal Barrier Dysfunction in High-Fat Feeding Mice

Liu

et al. 2022

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Mechanistically, the study reveals that glycodeoxycholic acid (GDCA) induces the secretion of IL-22 by ILC3s through GATA binding protein 3 [93]. Feeding mice with long-term HFD induces an elevated level of DCA, which leads to a decrease of ILC3s in ileal mucosa, along with reduced ileal IL-22 concentration [94]. Thus, in NAFLD patients, the elevated level of DCA indicates the unbalance of GDCA and DCA, which leads to the decreased abundance of ILC3s as well as less secretion of IL-22, and thus promotes the hepatic inflammation and affects the normal lipid metabolism [95].…”

Section: Advanced Gut and Microbiome Researchmentioning

confidence: 98%

Bile Acids: A Bridge Linking Gut Microbiota and NAFLD

Zhang

Wang

et al. 2022

Advanced Gut & Microbiome Research

View full text Add to dashboard Cite

Nowadays, nonalcoholic fatty liver disease (NAFLD) becomes the most common cause of liver disease worldwide. Mounting evidence indicates that dysbiosis contributes to the pathogenesis of NAFLD. Bile acids (BAs), the molecules that are first synthesized in hepatocytes and further metabolized by gut microbes, can either circulate in enterohepatic system or be found in circulations to exert various effects. Dysbiosis brings about the dysregulated BA composition, which is also observed in the pathology of NAFLD. As important signaling molecules, BAs bind to broadly expressed bile acid receptors (BARs) and play diverse roles in biological activity. Energy metabolism, immune system, and intestinal barrier function are affected by changes in BAs and their signaling pathways, which may explain the mechanisms of how altered BA pool affect NAFLD. Several novel NAFLD treatments targeting BA signaling are under development and their challenges and limitations are also discussed in this review.

show abstract

“…Mice fed a diet that increased DCA in the digesta showed damaged ILC3s and suppressed IL-22 production in ileum. 42 Inflammatory intestinal disease, involving diarrhea and ulcerative colitis, leads to increasing disruption of the mucosal barrier function, insulin resistance, altered BA metabolism, and reduced IL-22 secretion. 43 Dysmetabolism of BA in inflammatory bowel diseases is characterized by the enrichment of primary and conjugated BAs and the reduction of secondary BAs such as DCA and LCA.…”

Section: Food and Function Papermentioning

confidence: 99%

Curcumin alleviates LPS-induced intestinal homeostatic imbalance through reshaping gut microbiota structure and regulating group 3 innate lymphoid cells in chickens

Ruan

Fouad

et al. 2022

Food Funct.

View full text Add to dashboard Cite

show abstract

An elevated deoxycholic acid level induced by high-fat feeding damages intestinal stem cells by reducing the ileal IL-22

Cited by 14 publications

References 27 publications

Intestinal Stem Cells Damaged by Deoxycholic Acid via AHR Pathway Contributes to Mucosal Barrier Dysfunction in High-Fat Feeding Mice

Intestinal Stem Cells Damaged by Deoxycholic Acid via AHR Pathway Contributes to Mucosal Barrier Dysfunction in High-Fat Feeding Mice

Bile Acids: A Bridge Linking Gut Microbiota and NAFLD

Curcumin alleviates LPS-induced intestinal homeostatic imbalance through reshaping gut microbiota structure and regulating group 3 innate lymphoid cells in chickens

Contact Info

Product

Resources

About