Apple polyphenol product, phlorizin or procyanidin B₂, alleviates transplanted obese patient fecal microbiota-induced obesity in mice by modulating the gut microbiota and related phages

Apples are popular fruits worldwide and rich in phenolic compounds that can alleviate obesity and related metabolic diseases. However, the mechanisms underlying the anti-obesity actions of apple polyphenols (AP) like phlorizin (PZ) and procyanidin B₂ (PB2) on transplanted obese patient fecal microbiota (TOPFM)-induced obesity and related syndromes have not yet been fully examined in vivo. Herein, a commercial AP product, PZ compound or PB2 compound was used to ameliorate TOPFM-induced obesity in mice. The results indicated that the AP, PZ or PB2 supplementation markedly alleviate TOPFM-induced obesity in mice through effectively suppressing body weight gain and fat accumulation, alleviating insulin resistance and liver inflammation, regulating gut microecology and lipid synthesis/metabolism, and improving gut barrier function and antioxidant capacity. The gut barrier function and integrity were improved through regulating the expression of intestinal pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6), and gut barrier function-related genes, zonula occludens-1 (ZO-1) and Occludin, and raising the glucagon-like peptide 2 (GLP-2) level via increasing the contents of short-chain fatty acids (SCFAs). Interestingly, the AP, PZ or PB2 supplementation could significantly improve the production of SCFAs and restore the microbial community structure and diversity in mice with TOPFM-induced obesity, in particular, increased the abundance of Lachnospiraceae and Bifidobacteriaceae possibly by inhibiting Blautia and Bifidobacterium phages. The influences of AP, PZ or PB2 on gut microorganisms and phases of the mice upon TOPFM were species-specific. This study was the first report on the ability of an AP, PZ or PB2 supplementation to promote the production of SCFAs by modulating gut microbiota possibly via regulating gut phages.