Variation in the Plasma Levels of Polyunsaturated Fatty Acids in Control vis-à-vis Nonalcoholic Fatty Liver Disease Subjects and Its Possible Association with Gut Microbiome.

Abstract

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are becoming a major cause of chronic liver diseases globally. Polyunsaturated fatty acids (PUFA) have been postulated as a potential treatment for NAFLD. They can be obtained from diet and are also endogenously synthesized by enzymes delta-6-desaturase (D6D), delta-5-desaturase, and elongases. The current study is aimed at investigating the differences in the intake and levels of plasma PUFA between NAFLD patients and controls in Asian Indians. This correlation further propelled a pilot study to check for the differences in the gut microbiome of NASH subjects versus controls. One hundred forty-seven subjects were recruited and were grouped into healthy controls and cases. Subjects filled a food frequency questionnaire to assess PUFA intake. Plasma samples were subjected to gas chromatography analysis. For characterizing the gut microbiome, fecal samples of 20 NASH and healthy controls were analyzed by 16s rRNA gene sequencing. Alpha and beta diversity metrics and taxonomic analysis were carried out. Plasma levels of eicosapentaenoic acid, γ-linoleic acid and D6D enzyme activity were significantly lower in cases. Dietary intake of total n-6 and n-3 PUFA did not differ between the two groups. Relative abundance of Streptococcus and Clostridium ramosum was significantly higher in NASH patients compared with healthy controls. This study demonstrates, for the first time, decreased D6D enzyme activity and plasma PUFA levels in NAFLD patients. Furthermore, it demonstrates gut dysbiosis in histologically proven NASH patients vis-à-vis healthy controls.