Decreased Abundance of Lachnospira spp. Associated with Hepatitis and Increased HOMA-IR in Pediatric Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) in children is associated with severe metabolic syndrome and chronic liver disease. This study aimed to link gut dysbiosis with pediatric NAFLD and associated hepatitis. Children were divided into NAFLD and non-NAFLD groups using the noninvasive ultrasonographic fatty liver indicator (US-FLI) score. The abundance of Lachnospira spp., Faecalibacterium spp., Oscillospira spp., and Akkermansia spp. was significantly decreased in the NAFLD group, and Lachnospira spp. was concomitantly less abundant in children with NAFLD and hepatitis than in the respective control groups. Both NAFLD patients and NAFLD patients with hepatitis exhibited a decrease in the proportion of sequences associated with flavone and flavonol biosynthesis. Lachnospira spp. were positively correlated with flavone and flavonol biosynthesis and inversely correlated with insulin levels and HOMA-IR. Moreover, the body weight, BMI, and total cholesterol were negatively correlated with flavone and flavonol biosynthesis. This study revealed a lower abundance of Lachnospira spp. and flavone and flavonol biosynthesis-related pathways in children with NAFLD and in those with NAFLD with hepatitis. Decreased Lachnospira spp. may increase insulin resistance by negatively modulating flavone and flavonol biosynthesis-related functional pathways in pediatric NAFLD and contribute to chronic inflammation.