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Journal of Cancer Prevention

Original Article

J Cancer Prev 2021; 26(4): 277-288

Published online December 30, 2021

© Korean Society of Cancer Prevention

Fecal Microbial Enterotypes Differentially Respond to a High-fat Diet Based on Sex in Fischer-344 Rats

Soo In Choi1 , Nayoung Kim1,2 , Ryoung Hee Nam1 , Ji Hyun Park2 , Heewon Nho1 , Jeong Eun Yu1 , Chin-Hee Song1 , Sun Min Lee1 , Dong Ho Lee1,2

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, 2Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

Correspondence to :
Nayoung Kim, E-mail:,

Received: December 13, 2021; Revised: December 23, 2021; Accepted: December 24, 2021

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


The gut microbiota interacts with the host gut environment, which is influenced by such factors as sex, age, and host diet. These factors induce changes in the microbial composition. The aim of this study was to identify differences in the gut microbiome of Fisher-344 (F344) rats fed a high-fat diet (HFD), depending on their age and sex. Fecal microbiomes from 6-, 31-, and 74-week-old, and 2-year-old both male and female rats (corresponding to 5-, 30-, 60-, and 80-year-old humans) were analyzed using 16S rRNA gene sequencing, phylogenetic investigation of communities by reconstruction of unobserved states, and enterotype (E) assessment. Moreover, the effect of an HFD on colonic epithelial cells was measured using real-time quantitative PCR. Alpha diversity decreased in the HFD group regardless of age and sex. Based on the enterotype clustering of the whole fecal microbiome, clusters from male rats were divided into E1 and E2 enterotypes, while clusters from female rats were divided into E1, E2, and E3 enterotypes. The female E3 group showed a significantly high abundance in the Ruminococcus genus and expression of Tlr2 mRNA, which may reflect compensation to the HFD. Moreover, the female E3 group showed a lower ratio of opportunistic pathogenic strains to commensal strains compared to the female E2 group. Administration of an HFD influenced the rat fecal microbiota in all assessed age groups, which could be further differentiated by sex. In particular, female rats showed a compensatory enterotype response to an HFD compared to male rats.

Keywords: Rats, Diet, high-fat, Microbiota, Aging, Sex


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