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

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

doi:10.1016/j.jhepr.2022.100619

Cited by 10 publications

(7 citation statements)

References 43 publications

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“…Multivariate regression further showed that serum valine was an independent predictor of sarcopenia in liver cirrhosis even when we corrected for the severity of the liver disease. Consistent with our findings, the levels of serum BCAA are significantly reduced in cirrhotic patients with sarcopenia 36 . Additionally, BCAA supplementation improved muscle mass, and muscle strength, and increased skeletal protein synthesis in cirrhotic patients with sarcopenia 37 .…”

Section: Discussionsupporting

confidence: 90%

“…Consistent with our findings, the levels of serum BCAA are significantly reduced in cirrhotic patients with sarcopenia. 36 Additionally, BCAA supplementation improved muscle mass, and muscle strength, and increased skeletal protein synthesis in cirrhotic patients with sarcopenia. 37 In an in vitro gut model, B. ovatus and valine production correlated positively.…”

Section: Discussionmentioning

confidence: 99%

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Altered gut microbiome, bile acid composition and metabolome in sarcopenia in liver cirrhosis

Aliwa,

Horvath,

Traub

et al. 2023

J cachexia sarcopenia muscle

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BackgroundSarcopenia in liver cirrhosis is associated with low quality of life and high mortality risk. The pathogenesis has yet to be fully understood. We hypothesized that gut microbiome, bile acid (BA) composition and metabolites differ between cirrhotic patients with and without sarcopenia and contribute to pathogenesis.MethodsCirrhotic patients with (n = 78) and without (n = 38) sarcopenia and non‐cirrhotic controls with (n = 39) and without (n = 20) sarcopenia were included in this study. Faecal microbiome composition was studied by 16S rDNA sequencing, serum and faecal BA composition by ultra‐high‐performance liquid chromatography–tandem mass spectrometry, and metabolite composition in serum, faeces and urine by nuclear magnetic resonance.ResultsBacteroides fragilis, Blautia marseille, Sutterella spp. and Veillonella parvula were associated with cirrhotic patients with sarcopenia, whereas Bacteroides ovatus was more abundant in cirrhotic patients without sarcopenia. We observed significantly elevated secondary BAs, deoxycholic acid (DCA; P = 0.01) and lithocholic acid (LCA; P = 0.02), and the ratios of deoxycholic acid to cholic acid (DCA:CA; P = 0.04), lithocholic acid to chenodeoxycholic acid (LCA:CDCA; P = 0.03) and 12 alpha‐hydroxylated to non‐12 alpha‐hydroxylated BAs (12‐α‐OH:non‐12‐α‐OH BAs; P = 0.04) in serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia, indicating an enhanced transformation of primary to secondary BAs by the gut microbiome. CA (P = 0.02) and the ratios of CA:CDCA (P = 0.03) and total ursodeoxycholic acid to total secondary BAs (T‐UDCA:total‐sec‐BAs, P = 0.03) were significantly reduced in the stool of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia. Also, valine and acetate were significantly reduced in the serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia (P = 0.01 and P = 0.03, respectively). Multivariate logistic regression further confirmed the association of B. ovatus (P = 0.01, odds ratio [OR]: 12.8, 95% confidence interval [CI]: 168.1; 2.2), the ratios of 12‐α‐OH:non‐12‐α‐OH BAs (P = 0.03, OR: 2.54, 95% CI: 0.99; 6.55) and T‐UDCA:total‐sec‐BAs (P = 0.04, OR: 0.25, 95% CI: 0.06; 0.98) in serum and stool CA:CDCA (P = 0.04, OR: 0.79, 95% CI: 0.62; 0.99), and serum valine (P = 0.04, OR: 1.00, 95% CI: 1.02; 1.00) with sarcopenia in cirrhosis after correcting for the severity of liver disease and sex.ConclusionsOur study suggests a potential functional gut microbiome–host interaction linking sarcopenia with the altered gut microbiomes, BA profiles and amino acids pointing towards a potential mechanistic interplay in understanding sarcopenia pathogenesis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Altered gut microbiome, bile acid composition and metabolome in sarcopenia in liver cirrhosis

Aliwa,

Horvath,

Traub

et al. 2023

J cachexia sarcopenia muscle

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“…Наибольшее микробиологическое различие наблюдалось между пациентами с саркопенией и пациентами с нормальным мышечным статусом (р = 0,035). У лиц с саркопенией были более низкие уровни аланина, валина, лейцина, изолейцина, пролина, триптофана и орнитина в сыворотке крови [29].…”

Section: роль микробиоты кишечника в патогенезе саркопенииunclassified

“…Примечательно, что в исследовании Lee P.C. et al (2022), которое было рассмотрено выше, валин, лейцин, изолейцин -аминокислоты с разветвленной цепью -имели более низкую концентрацию в плазме крови у пациентов с саркопенией [29]. Таким образом, низкий уровень BCAA может быть ассоциирован с саркопенией.…”

Section: аминокислоты в качестве пищевых добавокunclassified

Nutritional support in a comprehensive program of prevention and treatment of sarcopenia

Kurmaev

Bulgakova

Treneva

et al. 2023

Rossiiskii zhurnal geriatricheskoi meditsiny

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Adequate nutrition with a high protein content is one of the main conditions in the complex treatment of sarcopenia. This review article considers strategies for maintaining the dietary derived protein and amino acids value in patients with sarcopenia. The features of nutritious diet in young, middle-aged and older people including those with sarcopenia are compared and outlined. The possibilities of nutritional supplements of proteins and amino acids in the diet of geriatric patients with sarcopenia are given.

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“…Previous studies have revealed that sarcopenia in cirrhosis patients may be attributed to liver metabolic dysfunction, reduced appetite, increased muscle autophagy, elevated serum myostatin levels, catabolic effects of systemic inflammation induced by intestinal bacterial translocation, and low testosterone levels ( 10 ). Sarcopenia in cirrhosis patients is associated with a grim prognosis ( 12 ), such as reduced quality of life, elevated hepatic venous pressure gradients, complications related to portal hypertension (such as ascites and upper gastrointestinal varices), infections (including urinary tract infections and spontaneous peritonitis) and HE ( 10 ). Reduced extrahepatic ammonia clearance in patients with sarcopenia may contribute to HE to some extent ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

Correlation between sarcopenia and cirrhosis: a meta-analysis

Cui,

Zhang,

Guo

et al. 2024

Front. Nutr.

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BackgroundThe relationship between sarcopenia and cirrhosis is unclear. In this research, our aim is to evaluate the prevalence of sarcopenia among individuals with liver cirrhosis and its correlation with survival and mortality risks.MethodsWe conducted searches on PubMed, Web of Science, EMBASE, and Cochrane for English articles published up to July 10, 2023, and additionally manually searched the bibliography of relevant articles. We incorporated research on sarcopenia in patients with cirrhosis to examine the connection between sarcopenia and the likelihood of survival and mortality. Statistical analyses were carried out utilizing the Stata version 15.1 software. Depending on the heterogeneity of the results, we employed either fixed-effects models or random-effects models for data synthesis. To assess publication bias, we employed funnel plots and conducted Egger’s test.ResultsWe included 40 studies involving 8,945 patients with cirrhosis. The overall prevalence of cirrhosis was 41% (95% CI 34%–48%). Male patients and those with liver cirrhosis and hepatic encephalopathy had a higher prevalence of sarcopenia (44% for male patients and 48% for hepatic encephalopathy patients). Sarcopenia emerged as a risk factor for both survival (HR = 2.57, 95% CI 2.02–3.27, p < 0.001) and mortality (HR = 2.13, 95% CI 1.86–2.44, p < 0.001) in patients with cirrhosis. Subgroup analyses consistently yielded the same results for study sites, whether HCC patients were excluded from the cohort, whether patients were from the liver transplant cohort or had undergone tips surgery, the definition of sarcopenia (L3-SMI or other methods), and the diagnostic criteria used by patients. The presence of sarcopenia was also a significant risk factor for hepatic encephalopathy [HR = 2.27, 95% CI (1.76–2.94), p < 0.001].ConclusionThis systematic review and meta-analysis reveal that patients with cirrhosis have a prevalence of sarcopenia of 41% and is associated with survival rate and mortality rate. Therefore, we should attach importance to the screening of sarcopenia in patients with cirrhosis, early detection of susceptible populations, and appropriate measures to reduce the occurrence and adverse outcomes.Systematic review registration:https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

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

Cited by 10 publications

References 43 publications

Altered gut microbiome, bile acid composition and metabolome in sarcopenia in liver cirrhosis

Altered gut microbiome, bile acid composition and metabolome in sarcopenia in liver cirrhosis

Nutritional support in a comprehensive program of prevention and treatment of sarcopenia

Correlation between sarcopenia and cirrhosis: a meta-analysis

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