Sex-specific association between the gut microbiome and high-fat diet-induced metabolic disorders in mice

Abstract

Background Accumulating evidence indicates that high-fat diet (HFD)-induced metabolic disorders are associated with dysbiosis of the gut microbiota. However, the sex-specific characteristics of the gut microbiota and its association with a sexually dimorphic response to a HFD remain unclear. Methods Male and female mice were randomly assigned to receive a chow diet (CD) or HFD for 12 weeks. A group of HFD mice were pretreated with antibiotic cocktails for 4 weeks. Body weight, insulin sensitivity and the levels of serum metabolic parameters (blood glucose and insulin) were evaluated. 16S rRNA gene sequencing was performed to analyze the composition of the gut microbiota. Results HFD-induced body weight gain (BWG) was higher in male mice than in female mice. While insulin resistance was increased in the HFD group compared to CD group in male mice, there was no difference in insulin resistance among female mice. Antibiotic-pretreatment alleviated HFD-induced insulin resistance in male mice and elevated fasting blood glucose in female mice. The composition of the gut microbiota in male mice was remarkably different from that in female mice independent of diet. A higher abundance of the genera Parabacteroides, Lactobacillus, Bacteroides, and Bifidobacterium was observed in females than inmales. HFD feeding also influenced the structure of the gut microbiota, as it decreased the abundance of short-chain fatty acids-producing bacteria including Roseburia and Lachnospiraceae_NK4A136_group. Alterations in the gut microbiota in response to antibiotics followed by HFD were different between males and females, indicating sex-dependent sensitivity to antibiotics. Conclusions We identified that sex had a greater impact on the composition of gut microbiota than environmental factors (HFD and antibiotics). The enrichment of beneficial microbes in female mice may be associated with the resistance of female mice to HFD-induced metabolic disorders, which was weakened by antibiotic pretreatment.

Relationship between gut environment, feces-to-food ratio, and androgen deficiency-induced metabolic disorders

“…5,6 Sex-related differences have been reported in the composition of gut microbiota for both rodents and humans. [7][8][9][10][11][12][13][14][15][16] Decrease in αdiversity of microbiota in the gut is associated with obesity, 17,18 and α-diversity is lower on average in males compared to females, [10][11][12]14 especially in young adults (ages 20 to 45 years) compared to middle-aged adults. 10 The effect of sex on gut microbiota composition is larger than that observed in response to a high-fat diet (HFD) or treatment with antibiotics, 8 but is smaller than effects due to genotype.…”

“… 14 , 15 Sex differences in gut microbiota are also suggested to play a role in the development of other diseases that show a sex bias, including rheumatoid arthritis, 19 anxiety disorder, 20 hepatocellular carcinoma, 21 and inflammatory bowel disease. 11 , 22 Sex-by-diet interactions in gut microbiota have been observed in C57BL/6 J mice 7 , 8 and humans, 9 and gut microbiota play a critical role in HFD-induced obesity and insulin resistance. 23 The combinatorial effects of androgen and diet may therefore induce pathological conditions that have a sex bias through modulation of gut microbiota.…”

Modulation of Gut Microbiota in Korean Navy Trainees following a Healthy Lifestyle Change

“…Holdemanella spp. has been reported to be positively associated with chronic kidney disease [65] and the android fat ratio in male [66], and Turicibacter spp. were positively associated with inflammation [67].…”

Ear wound healing in MRL/MpJ mice is associated with gut microbiome composition and is transferable to non-healer mice via microbiome transplantation

“…Previous studies have highlighted a reduction in OA histopathologic severity in female mice, in both young and old animals [43,44]. Although not evaluated directly in the context of OA, sex-specific differences in the gut microbiome have been described in association with known OA risk factors, including high fat diet-induced obesity [45,46] and advanced age [47]. In the present study, our 16S analysis identified 18 sex-associated microbiome clades; among these, 7 overlapped with our MRL vs. B6 comparison.…”