Abstract
Background
Although we know the key role of gut dysbiosis in nonalcoholic fatty liver disease (NAFLD), it remains unclear what microbe(s) are responsible. This study aims to identify the microbes that cause NAFLD.
Methods
C57BL/6JNarl male mice fed a high-fat diet (HFD) were orally administered Lactobacillus reuteri (L. reuteri) or Lactobacillus rhamnosus GG plus Bifidobacterium animalis subsp. lactis BB12 (LGG plus BB12). Their fecal microbiomes identified by 16S rRNA sequencing were correlated with the severity of fatty liver. We then used a human cohort to confirm the role of the microbe(s). The HFD-fed mice were administrated with the identified bacterium, Desulfovibrio. The histopathological changes in the liver and ileum were analyzed.
Results
Lactobacillus and Bifidobacterium improved hepatic steatosis and fibrosis in HFD-fed mice, which was related to the decreased abundance of Desulfovibrio in feces. Further human study confirmed the amount of D. piger in the fecal microbiota of obese children with NAFLD was increased. We then administered D. piger and found aggravated hepatic steatosis and fibrosis in HFD-fed mice. Hepatic expression of CD36 was significantly increased in HFD-fed mice gavaged with D. piger. In HepG2 cells, overexpression of CD36 increased lipid droplets, whereas knockdown of CD36 decreased lipid droplets. HFD-fed mice gavaged with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 density in the ileum tissue.
Conclusions
Our findings provide novel insights into the role of Desulfovibrio dysregulation in NAFLD. Modulation of Desulfovibrio may be a potential target for the treatment of NAFLD.
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Acknowledgements
We appreciated Dr. Yu-Lun Kuo at BIOTOOLS Co., Ltd in Taiwan for supporting the analysis of 16S rRNA sequencing data, Dr. Yung-Ming Jeng at the Department of Pathology, National Taiwan University Hospital for interpreting the NAS of mouse liver tissues, and all support and equipment from the Core Laboratory and Animal Laboratory of Far Eastern Memorial Hospital, Taiwan. This work was supported by the Ministry of Science and Technology, Executive Yuan, Taiwan under Grant [MOST 107-2314-B-418-012-MY2, MOST 109-2314-B-418-009-MY3]; Far Eastern Memorial Hospital, Taiwan under Grant [FEMH 107-2314-B-418-012-MY2, FEMH 109-2314-B-418-009 -MY3, FEMH-2021-C-012]; and Far Eastern Memorial Hospital—National Taiwan University Hospital Joint Research Program under Grant [107-FTN02, 108-FTN11, 109-FTN07].
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The authors’ responsibilities were as follows — Y-CL and Y-HN designed research; Y-CL, H-FL and C-LC conducted research; Y-CL and C-CW analyzed data; Y-CL wrote the paper; Y-HN had primary responsibility for the final content of the manuscript. All authors read and approved the final manuscript.
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Lin, YC., Lin, HF., Wu, CC. et al. Pathogenic effects of Desulfovibrio in the gut on fatty liver in diet-induced obese mice and children with obesity. J Gastroenterol 57, 913–925 (2022). https://doi.org/10.1007/s00535-022-01909-0
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DOI: https://doi.org/10.1007/s00535-022-01909-0