Sex is associated with differences in gut microbial composition and function in hepatic encephalopathy
| Autor: | Douglas M. Heuman, Patrick M. Gillevet, Andrew Fagan, Melanie B. White, Edith Gavis, Ravishankar K. Iyer, Krishnakant Saboo, Mihir V. Iyer, Jasmohan S. Bajaj, Michael Fuchs, Masoumeh Sikaroodi, Amirhossein Shamsaddini, Chang Hu |
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| Rok vydání: | 2021 |
| Předmět: |
Liver Cirrhosis
Male 0301 basic medicine Cirrhosis medicine.drug_class Physiology Disease Article Rifaximin End Stage Liver Disease 03 medical and health sciences chemistry.chemical_compound Lactulose Liver disease Sex Factors 0302 clinical medicine Gastrointestinal Agents RNA Ribosomal 16S Brain-Gut Axis medicine Humans Hormone metabolism Correlation of Data Hepatic encephalopathy Hepatology Sequence Analysis RNA business.industry Middle Aged medicine.disease Androgen Gastrointestinal Microbiome Cross-Sectional Studies 030104 developmental biology chemistry Hepatic Encephalopathy Female 030211 gastroenterology & hepatology business medicine.drug |
| Zdroj: | J Hepatol |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/j.jhep.2020.06.046 |
| Popis: | Background & Aims Altered microbiota can affect the gut-liver-brain axis in cirrhosis and hepatic encephalopathy (HE), but the impact of sex on these changes is unclear. We aimed to determine differences in fecal microbiota composition/functionality between men and women with cirrhosis and HE on differing treatments. Methods Cross-sectional stool microbiome composition (16s rRNA sequencing) and microbial functional analyses were performed in men and women with cirrhosis, and controls. Patients with HE on rifaximin+lactulose (HE-Rif), patients with HE on lactulose only (HE-Lac) and those with cirrhosis without HE (No-HE) were compared to controls using random forest classifier. Men and women were also compared. Results A total of 761 individuals were included, 619 with cirrhosis (466 men, 153 women) and 142 controls (92 men, 50 women). Men were older and more frequently used proton pump inhibitors (PPIs), but model for end-stage liver disease score, No-HE (n = 319), HE-lac (n = 130) and HE-Rif (n = 170) proportions were similar. PPI/age-adjusted AUC of differentiation between controls vs. all cirrhosis, and controls vs. No-HE were higher within women than men, but the adjusted AUC for No-HE vs. HE-Rif was higher in men. Control vs. HE-Rif differentiation was similar across sexes. Men vs. women were different in all cirrhosis, No-HE and HE-Lac but not HE-Rif on PERMANOVA and AUC analyses. Autochthonous taxa decreased and pathobionts increased with disease progression regardless of sex. In men, Lactobacillaceae were higher in HE-Lac but decreased in HE-Rif, along with Veillonellaceae. Pathways related to glutamate and aromatic compound degradation were higher in men at all stages. Degradation of androstenedione, an estrogenic precursor, was lower in men vs. women in HE-Rif, likely enhancing feminization. Conclusions There are differences in gut microbial function and composition between men and women with cirrhosis, which could be implicated in differential responses to HE therapies. Further studies linking these differences to sex-specific outcomes are needed. Lay summary Patients with cirrhosis develop changes in their brain function, and men often develop feminization with disease progression. However, the interaction between sex, microbiota and disease severity is unclear. We found that as disease progressed in men, their microbial composition began to approach that observed in women, with changes in specific microbes that are associated with male hormone metabolism. |
| Databáze: | OpenAIRE |
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