Abstract
Gut microbiota, an important component that affects host health, change rapidly and directly in response to altered diet composition. Recently, the role of diet–microbiome interaction on the development of colon cancer has been the focus of interest. Colon cancer occurs more frequently in an aged population, and in males. However, the effect of dietary changes on the gut microbiome has been studied mainly in young males, even though it may vary with age and sex. The aim of this study was to investigate microbial changes and host response in the colons of male and female 6-week-old (young) and 2-year-old (old) Fisher-344 rats exposed to a high-fat diet (HFD). Our results showed that exposure to HFD for 8 weeks decreased the species richness of microbiota (Chao1) and increased Firmicutes/Bacteroidetes ratio only in aged rats, and not in young rats. Sex differences underlying the alteration by HFD in the gut microbiome were observed in the microbiome of aged rats. For instance, the abundance ratio of Akkermansia muciniphila and Desulfovibrio spp. increased in response to HFD in young rats and female aged rats, but not in male aged rats. Histological inflammation and cell proliferation of colon mucosa (indexed by Ki67) were significantly increased by HFD even in young rats; aged rats showed significantly higher cell proliferation in the HFD group than in the control. The HFD-induced decrease of species richness and the increase in specific species (Desulfovibrio spp. and Clostridium lavalense), which produce carcinogenic compounds such as H2S and N-nitroso compounds, were significantly correlated with Ki67 index. In colon mucosa, the concentration of myeloperoxidase was increased by HFD only in males, and not in females. In conclusion, the results suggest a link between HFD-induced gut dysbiosis (particularly the low species richness and high abundance ratios of Desulfovibrio spp. and C. lavalense) and cell proliferation of colon mucosa (indicated by Ki67 IHC). In addition, sex differences influence the response of gut microbiome to HFD particularly in old age. Such sex differences in the gut microbiota might be related to sex differences in inflammation in the colon mucosa.
Highlights
Gut Microbial Changes Occurring in Rats of Different Sex and Age Following a High-Fat DietMicrobiota composition changes with age (Bischoff, 2016) and gut dysbiosis influences aged guts by promoting gut permeability and inflammation (Thevaranjan et al, 2017)
The weight gain of 6-week-old rats and 2-year-old female rats was significantly higher in high-fat diet (HFD)-fed rats than in rats fed with control diet; by contrast, it was not increased by HFD in 2year-old male rats (p < 0.001 to Kruskal–Wallis test; 6-weekold male: p = 0.010; 6-week-old female: p = 0.010; 2-year-old male: p = 0.243; 2-year-old female: p = 0.014)
The Ki67 cell proliferation index in colonic mucosa was increased with HFD, and the rate was higher in aged male rats than in young male rats
Summary
Gut Microbial Changes Occurring in Rats of Different Sex and Age Following a High-Fat DietMicrobiota composition changes with age (Bischoff, 2016) and gut dysbiosis influences aged guts by promoting gut permeability and inflammation (Thevaranjan et al, 2017). Recent studies have reported sex differences in gut microbiota composition with varying results (Lay et al, 2005; Mueller et al, 2006; Li et al, 2008; Kovacs et al, 2011; Bolnick et al, 2014; Shastri et al, 2015; Org et al, 2016). In 8week-old mice of 89 different strains, the role of sex differences in gut microbiota composition was demonstrated by grouping microbial communities based on the effects of gonadectomy and hormone treatment (Org et al, 2016). The effects of dietary change on gut microbiota were sex-dependent in fish and mice aged 9 months and 8 weeks, respectively (Bolnick et al, 2014)
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