Pirola Carlos Jose, Landa Maria Silvina, Schuman Mariano, García Silvia Inés, Salatino Adrian, Sookoian Silvia
Systems Biology of Complex Diseases, Translational Research in Health Center (CENITRES). Maimónides University, Buenos Aires, Argentin.
National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
Clin Mol Hepatol. 2025 Jan;31(1):179-195. doi: 10.3350/cmh.2024.0359. Epub 2024 Oct 11.
BACKGROUND/AIMS: 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.
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.
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.
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.
背景/目的：有证据表明，胃肠道微生物群在代谢功能障碍相关脂肪性肝病（MASLD）的生物学过程中起重要作用。然而，性别之间肠道组织各部分的肠道微生物群差异是否会导致MASLD发病仍不清楚。
使用MASLD实验模型，对肠道两个解剖学上不同区域（小肠和结肠）的微生物群组成进行性别特异性分析。该研究涉及雄性和雌性自发性高血压大鼠以及Wistar-Kyoto对照大鼠品系，将它们分别喂食标准饲料或高脂饲料12周以诱导MASLD（每组12只大鼠）。采用高通量16S测序进行微生物群分析。
患有MASLD的雄性和雌性大鼠的整体微生物群组成存在显著差异，包括肠道不同区域的变化。雌性大鼠空肠和结肠微生物群的β多样性高于雄性大鼠（PERMANOVA p值=0.001）。使用LEfSe进行的性别特异性分析和判别特征显示，患有MASLD的动物空肠和结肠中的细菌丰度存在相当大的差异，以及不同的功能特性。与雌性MASLD大鼠相比，雄性MASLD大鼠肝脏中的脂多糖水平和Toll样受体4的蛋白表达显著升高。
本研究揭示了MASLD肠道微生物群中的性别二态性，并确定了肠道各部分内的微生物异质性。对肠道微生物群组成中性别特异性差异的深入了解有助于制定个性化治疗策略。
