Double-blind randomized placebo-controlled supplementation of a standardized Terminalia chebula fruit extract alters the gut microbiome, phageome, and increases short chain fatty acids in High-BMI, borderline diabetic females

Abstract

Terminalia chebula (TC) is an Ayurvedic herb containing polyphenolic compounds that interact with gut microbiota to modulate bioactivity. To examine how TC supplementation modulates the gut microbiome and associated metabolic pathways, a double-blind, randomized, placebo-controlled study that screened 58 and enrolled 43 females aged 25–55 with a BMI of 25–35 kg/m2 and HbA1C between 5.5–7. Subjects were randomized to standardized preparation of TC (250 mg, Synastol® TC) capsules or oral placebo twice daily for 8 weeks. Stool sample collections and venipuncture were performed. Α-diversity of the gut microbiome increased in the TC group at week 8 versus placebo (p < 0.05). Akkermansia muciniphila, Alistipes_putredinis, Bacteroides_u_s, Ruminococcaceae_u_s, Waltera_intestinalis, Lachnospira_eligens, Parabacteroides phage YZ-2015b and Uncultured_crAssphage increased at week 8 versus baseline following TC supplementation. Circulating acetic acid (p < 0.05), propionic acid (p < 0.01), and butyric acid (p = 0.12) increased at week 8 in the TC group versus placebo. Chenodeoxycholate and tauro-beta-muricholate increased following TC supplementation (p < 0.05). TC supplementation increases beneficial gut bacteria, phages, and circulating SCFAs, which may modulate bile acid synthesis. Future studies on how TC extract supplementation influences the metabolome in an expanded population are warranted.