Abstract
There is evidence that nonalcoholic fatty liver disease (NAFLD) is affected by gut microbiota, glucose, and lipid. However, the function of water-electrolyte metabolism remains undefined in children with NAFLD. Therefore, the aim of this case-control study was to better understand these interactions. The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without NAFLD. These groups were matched by age, sex, and body mass index. Data were collected between June, 2019 and December, 2019 at the Hunan Children’s Hospital, in China. Microbiome composition in fecal samples was assessed using 16S ribosomal RNA amplicon sequencing. In the clinical indices, 12 glucose and lipid metabolism indices were included, and six water-electrolyte metabolism indices were included. The results indicated that microbiomes of NAFLD children had lower alpha diversity but higher beta diversity index than the other two groups. Specifically, anti-inflammatory and probiotics abundance (e.g., Faecalibacterium, Akkermansia, and Bifidobacterium_adolescentis) was significantly decreased in NAFLD, whereas the abundance of harmful bacteria (e.g., Staphylococcaceae) was increased. Moreover, the abundance of butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia_inulinivorans, Roseburia_intestinalis, and Coprococcus_comes) was significantly decreased in NASH. The abundance of these bacteria were associated with glucose, lipid, and water-electrolyte metabolism (e.g., glucose, triglyceride, cholesterol, inorganic salt, total body water, etc.), implying that the NAFLD and its severity were associated with glucose, lipid, and water-electrolyte metabolism dysbiosis. Therefore, these findings suggest that the gut microbiome, especially butyrate-producing bacteria, play an important role in the development of NAFLD in children.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in children worldwide (Schwimmer et al, 2019b)
The sample consisted of 75 children, aged between 7 and 16, of whom 25 had nonalcoholic fatty liver (NAFL), 25 had nonalcoholic steatohepatitis (NASH), and 25 were obese and without nonalcoholic fatty liver disease (NAFLD)
For the NAFL cases and controls, abundance of the Verrucomicrobia at the phylum level; Verrucomicrobiae at the class level; Verrucomicrobiales and Pasteurellales at the order level; three bacteria (e.g., Akkermansiaceae and Pasteurellaceae) at the family level; seven bacteria (e.g., Akkermansia and Haemophilus) at the genus level; and Clostridium_unclassified at the species level was lower in the cases, whereas abundance of the Enterococcaceae and Staphylococcaceae at the family level and Novosphingobium and Peptoniphilus at the genus level was lower in the controls
Summary
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease in children worldwide (Schwimmer et al, 2019b). A comprehensive understanding as to why certain children develop NAFLD is lacking, which has spurred multidisciplinary research to better understand the intricate NAFLD pathogenesis. Recent studies have proposed high blood pressure as a potentially key player in the development of NAFLD (Schwimmer et al, 2014). This is due to the fact that hypertension may lead to altered intrahepatic splanchnic circulation and increased intrahepatic vascular resistance, which could induce NAFL to develop into NASH, cirrhosis and portal hypertension (Aneni et al, 2015). Gutliver axis (GLA) dysfunction (e.g., gut ecosystem dysbiosis, alteration of mucosa permeability, and bacterial overgrowth) may contribute to the rising portal pressure in the earliest stages of NAFL, albeit the mechanism of these changes remains unclear (Baffy, 2019; Schwimmer et al, 2019a)
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