AUTHOR=Zhang Lilong , Zi Liuliu , Kuang Tianrui , Wang Kunpeng , Qiu Zhendong , Wu Zhongkai , Liu Li , Liu Rongqiang , Wang Peng , Wang Weixing 

TITLE=Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1159148

DOI=10.3389/fendo.2023.1159148

ISSN=1664-2392

ABSTRACT=<sec><title>Objective</title><p>There is some evidence for an association between gut microbiota and nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and viral hepatitis, but no studies have explored their causal relationship.</p></sec><sec><title>Methods</title><p>Instrumental variables of the gut microbiota (N = 13266) and gut microbiota-derived metabolites (N = 7824) were acquired, and a Mendelian randomization study was performed to explore their influence on NAFLD (1483 European cases and 17,781 European controls), ALD (2513 European cases and 332,951 European controls), and viral hepatitis risk (1971 European cases and 340,528 European controls). The main method for examining causality is inverse variance weighting (IVW).</p></sec><sec><title>Results</title><p>IVW results confirmed that <italic>Anaerotruncus</italic> (<italic>p</italic> = 0.0249), <italic>Intestinimonas</italic> (<italic>p</italic> = 0.0237), <italic>Lachnoclostridium</italic> (<italic>p</italic> = 0.0245), <italic>Lachnospiraceae NC2004 group</italic> (<italic>p</italic> = 0.0083), <italic>Olsenella</italic> (<italic>p</italic> = 0.0163), and <italic>Peptococcus</italic> (<italic>p</italic> = 0.0472) were protective factors for NAFLD, and <italic>Ruminococcus 1</italic> (<italic>p</italic> = 0.0120) was detrimental for NAFLD. The higher abundance of three genera, <italic>Lachnospira</italic> (<italic>p</italic> = 0.0388), <italic>Desulfovibrio</italic> (<italic>p</italic> = 0.0252), and <italic>Ruminococcus torques group</italic> (<italic>p</italic> = 0.0364), was correlated with a lower risk of ALD, while <italic>Ruminococcaceae UCG 002</italic> level was associated with a higher risk of ALD (<italic>p</italic> = 0.0371). The <italic>Alistipes</italic> (<italic>p</italic> = 0.0069) and <italic>Ruminococcaceae NK4A214 group</italic> (<italic>p</italic> = 0.0195) were related to a higher risk of viral hepatitis. Besides, alanine (<italic>p</italic> = 0.0076) and phenyllactate (<italic>p</italic> = 0.0100) were found to be negatively correlated with NAFLD, while stachydrine (O<italic>p</italic> = 0.0244) was found to be positively associated with NAFLD. The phenylacetate (<italic>p</italic> = 0.0353) and ursodeoxycholate (<italic>p</italic> = 0.0144) had a protective effect on ALD, while the threonate (<italic>p</italic> = 0.0370) exerted a detrimental influence on ALD. The IVW estimates of alanine (<italic>p</italic> = 0.0408) and cholate (<italic>p</italic> = 0.0293) showed their suggestive harmful effects against viral hepatitis, while threonate (<italic>p</italic> = 0.0401) displayed its suggestive protective effect against viral hepatitis.</p></sec><sec><title>Conclusion</title><p>In conclusion, our research supported causal links between the gut microbiome and its metabolites and NAFLD, ALD, and viral hepatitis.</p></sec>