Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis

Pei-Chang Lee; Kuei-Chuan Lee; Tsung-Chieh Yang; Hsiao-Sheng Lu; Tsung-Yi Cheng; Yu-Jen Chen; Jen-Jie Chiou; Chi-Wei Huang; Ueng-Cheng Yang; Elise Chia-Hui Tan; Shih-Hsuan Chou; Yu-Lun Kuo; Bernd Schnabl; Yi-Hsiang Huang; Ming-Chih Hou

doi:10.1016/j.jhepr.2022.100619

Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis

JHEP Rep. 2022 Oct 29;5(1):100619. doi: 10.1016/j.jhepr.2022.100619. eCollection 2023 Jan.

Authors

Pei-Chang Lee^{1

2}, Kuei-Chuan Lee^{1

2}, Tsung-Chieh Yang^{1

2}, Hsiao-Sheng Lu^{1

2}, Tsung-Yi Cheng^{1

2}, Yu-Jen Chen^{1

2}, Jen-Jie Chiou³, Chi-Wei Huang³, Ueng-Cheng Yang³, Elise Chia-Hui Tan⁴, Shih-Hsuan Chou⁵, Yu-Lun Kuo⁵, Bernd Schnabl⁶, Yi-Hsiang Huang^{1

2

7}, Ming-Chih Hou^{1

2}

Affiliations

¹ Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
² School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁴ Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan.
⁵ Biotools, Co, Ltd, New Taipei City, Taiwan.
⁶ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
⁷ Institute of Clinical Medicine; College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Abstract

Background & aims: Sarcopenia and gut dysbiosis are common in individuals with cirrhosis. However, the association between sarcopenia and microbial alterations, and the subsequent impact on cirrhotic outcomes are poorly understood. This study aimed to identify muscle-dependent microbial changes and related risks of cirrhotic complications.

Methods: From September 2018 to December 2020, 89 individuals with cirrhosis and 16 healthy volunteers were prospectively enrolled. Muscle and nutritional status, serum amino acids, and fecal microbiota were analyzed. The association between microbial signatures of sarcopenia and cirrhotic complications was investigated.

Results: A decline in muscle mass and strength were associated with gut microbial alterations in individuals with cirrhosis. The greatest microbial dissimilarity was observed between those with sarcopenia (both decline in muscle mass and strength) and those with normal-muscle status (p = 0.035). Individuals with sarcopenia had lower serum levels of alanine, valine, leucine, isoleucine, proline, tryptophan and ornithine. Besides, gut microbial functions associated with amino acid biosynthesis were significantly reduced in individuals with sarcopenia and cirrhosis. Depletion of Dialister, Ruminococcus 2, and Anaerostipes were associated with cirrhotic sarcopenia, and significantly correlated with the serum levels of amino acids. Individuals with coexistent depletion of Ruminococcus 2 and Anaerostipes developed more infectious (44.4% vs. 3.0%) and non-infectious (74.1% vs. 3.0%) complications, and more hospitalizations (54 vs. 3) than those with cirrhosis with good microbial signatures (all p <0.001). In contrast, fecal enrichment of Ruminococcus 2 and Anaerostipes independently decreased the risk of 1-year complications.

Conclusions: Sarcopenia-related fecal microbial alterations are associated with cirrhotic complications. These findings may facilitate measures to improve the outcomes of individuals with cirrhosis and sarcopenia by modifying gut microbiota.

Impact and implications: The composition and biosynthetic functions of gut microbiota are significantly changed in individuals with sarcopenic cirrhosis. Those with a sarcopenia-related poor microbial signature, in which Ruminococcus 2 and Anaerostipes were both depleted, had significantly more infectious and non-infectious complications, as well as more hospitalizations. These findings highlight the therapeutic potential of modifying the gut microbiota of individuals with sarcopenic cirrhosis to improve their clinical outcomes.

Keywords: (A)SMI, (appendicular) skeletal muscle index; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Anaerostipes; Cirrhotic complications; HE, hepatic encephalopathy; MNA, mini-nutritional assessment; MUST, malnutrition universal screening tool; Microbiota; OR, odds ratio; PICRUSt2, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States version 2; Ruminococcus 2; SGA, subjective global assessment; Sarcopenia.

Abstract

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