Metabolic dysfunction-associated steatotic liver disease exhibits sex-specific microbial heterogeneity within intestinal compartments.

IF 14 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Clinical and Molecular Hepatology Pub Date : 2024-10-11 DOI:10.3350/cmh.2024.0359
Carlos Jose Pirola, Maria Silvina Landa, Mariano Schuman, Silvia Inés García, Adrian Salatino, Silvia Sookoian
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Abstract

Background: Evidence suggests that the gastrointestinal microbiome plays a significant role in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether disparities in the gut microbiome across intestinal tissular compartments between the sexes lead to MASLD pathogenesis.

Methods: Sex-specific analyses of microbiome composition in two anatomically distinct regions of the gut, the small intestine and colon, were performed using an experimental model of MASLD. The study involved male and female spontaneously hypertensive rats and the Wistar-Kyoto control rat strain, which were fed either a standard chow diet or a high-fat diet for 12 weeks to induce MASLD (12 rats per group). High-throughput 16S sequencing was used for microbiome analysis.

Results: There were significant differences in the overall microbiome composition of male and female rats with MASLD, including variations in topographical gut regions. The beta diversity of the jejunal and colon microbiomes was higher in female rats than in male rats (PERMANOVA p-value=0.001). Sex-specific analysis and discriminant features using LEfSe showed considerable variation in bacterial abundance, along with distinct functional properties, in the jejunum and colon of animals with MASLD. Significantly elevated levels of lipopolysaccharide and protein expression of Toll-like receptor 4 were observed in the livers of male rats with MASLD compared with their female counterparts.

Conclusion: This study uncovered sexual dimorphism in the gut microbiome of MASLD and identified microbial heterogeneity within intestinal compartments. Insights into sex-specific variations in gut microbiome composition could facilitate customised treatment strategies.

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代谢功能障碍相关性脂肪肝在肠道内表现出性别特异性微生物异质性。
背景:有证据表明,胃肠道微生物组在代谢功能障碍相关性脂肪性肝病(MASLD)的生物学过程中发挥着重要作用。然而,目前仍不清楚不同性别肠道微生物组之间的差异是否会导致 MASLD 发病:方法:利用一种 MASLD 实验模型,对小肠和结肠这两个解剖学上截然不同的肠道区域的微生物组组成进行了性别特异性分析。该研究涉及雌雄自发性高血压大鼠和 Wistar-Kyoto 对照品系大鼠,它们被喂食标准饲料或高脂肪饲料 12 周以诱导 MASLD(每组 12 只大鼠)。高通量 16S 测序用于微生物组分析:结果:患有 MASLD 的雌雄大鼠的整体微生物组组成存在明显差异,包括肠道地形区域的差异。雌性大鼠空肠和结肠微生物组的贝塔多样性高于雄性大鼠(PERMANOVA p-value=0.001)。使用 LEfSe 进行的性别特异性分析和判别特征显示,MASLD 动物空肠和结肠中的细菌丰度存在相当大的差异,而且功能特性也各不相同。在患有 MASLD 的雄性大鼠肝脏中观察到的脂多糖和 Toll 样受体 4 蛋白表达水平明显高于雌性大鼠:这项研究发现了MASLD肠道微生物组的性别双态性,并确定了肠道内微生物的异质性。了解肠道微生物组组成的性别特异性变化有助于制定个性化的治疗策略。
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来源期刊
Clinical and Molecular Hepatology
Clinical and Molecular Hepatology Medicine-Hepatology
CiteScore
15.60
自引率
9.00%
发文量
89
审稿时长
10 weeks
期刊介绍: Clinical and Molecular Hepatology is an internationally recognized, peer-reviewed, open-access journal published quarterly in English. Its mission is to disseminate cutting-edge knowledge, trends, and insights into hepatobiliary diseases, fostering an inclusive academic platform for robust debate and discussion among clinical practitioners, translational researchers, and basic scientists. With a multidisciplinary approach, the journal strives to enhance public health, particularly in the resource-limited Asia-Pacific region, which faces significant challenges such as high prevalence of B viral infection and hepatocellular carcinoma. Furthermore, Clinical and Molecular Hepatology prioritizes epidemiological studies of hepatobiliary diseases across diverse regions including East Asia, North Asia, Southeast Asia, Central Asia, South Asia, Southwest Asia, Pacific, Africa, Central Europe, Eastern Europe, Central America, and South America. The journal publishes a wide range of content, including original research papers, meta-analyses, letters to the editor, case reports, reviews, guidelines, editorials, and liver images and pathology, encompassing all facets of hepatology.
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