Dissecting the impact of dietary fiber type on atherosclerosis in mice colonized with different gut microbial communities

Abstract

Dietary fiber consumption has been linked with improved cardiometabolic health, however, human studies have reported large interindividual variations in the observed benefits. We tested whether the effects of dietary fiber on atherosclerosis are influenced by the gut microbiome. We colonized germ-free ApoE−/− mice with fecal samples from three human donors (DonA, DonB, and DonC) and fed them diets supplemented with either a mix of 5 fermentable fibers (FF) or non-fermentable cellulose control (CC) diet. We found that DonA-colonized mice had reduced atherosclerosis burden with FF feeding compared to their CC-fed counterparts, whereas the type of fiber did not affect atherosclerosis in mice colonized with microbiota from the other donors. Microbial shifts associated with FF feeding in DonA mice were characterized by higher relative abundances of butyrate-producing taxa, higher butyrate levels, and enrichment of genes involved in synthesis of B vitamins. Our results suggest that atheroprotection in response to FF is not universal and is influenced by the gut microbiome.

The gut microbiome modulates the impact of Anaerobutyricum soehngenii supplementation on glucose homeostasis in mice

“…S1c). These findings are consistent with engraftments reported in previous studies using human fecal samples to colonize mice 31 , 32 and indicate that cohousing recipient mice for 8 weeks was successful in achieving uniform microbial colonization within each donor group.…”

“…Groups of germ-free (GF) C57BL/6 mice were placed on a high-fat diet (HFD, 45% kcal from fat) at 5 weeks of age and colonized via oral gavage with fecal slurries generated from one of four human donor samples (R65, R55, N96, or N40; n = 9–10 mice per donor group). A common challenge with experiments involving GF mice colonized with complex microbial communities is inconsistent colonization between individual recipient mice, especially when mice are housed in separate cages 31 . Variable colonization is a confounding factor that can limit interpretation of treatment effects; therefore, it is important to confirm that the microbial communities are similar between all mice within each donor group prior to starting treatment.…”

“…Cecal levels of SCFAs were measured by headspace gas chromatography as previously described 31 . Briefly, frozen cecal contents (20–50 mg) were weighed and added to vials (Restek, Bellefonte, PA) containing 2.0 g of H 2 SO 4 and a volume a water such that the total volume was equal to 300 mL (Cecal content [mg] + water [mL] = 300).…”

Shaping human gut community assembly and butyrate production by controlling the arginine dihydrolase pathway

“…The column used was an SH-Stabilwax (30 m, 0.25 mm internal diameter, 0.10 µM film thickness). The GC protocol used is described in Hutchison et al (2023) 67 . Standards for acetate, propionate, isobutyrate, butyrate, isovalerate, and valerate were combined and serially diluted to generate a standard curve.…”

Systems genetics approach uncovers associations between host amylase locus, gut microbiome and metabolic traits in hyperlipidemic mice

“…Dietary compounds that cannot be digested by host enzymes, including plant polysaccharides and resistant starches, reach the distal gut where they are broken down and fermented by resident bacteria 9 . Consumption of different carbohydrates can influence the gut microbiota and its association with the host 10,11 . Non-digestible carbohydrates such as dietary fibers resist host digestion and can therefore serve as substrates for microbiota in the distal gut.…”