Effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease development.
OBJECTIVE
To study the effects of different diets on intestinal microbiota and nonalcoholic fatty liver disease (NAFLD) development at the same caloric intake.


METHODS
Thirty male Sprague-Dawley rats were randomized into five groups (six rats each). The control diet (CON) group and free high-fat diet (FFAT) group were allowed ad libitum access to a normal chow diet and a high-fat diet, respectively. The restrictive high-fat diet (RFAT) group, restrictive high-sugar diet (RSUG) group, and high-protein diet (PRO) group were fed a high-fat diet, a high-sugar diet, and a high-protein diet, respectively, in an isocaloric way. All rats were killed at 12 wk. Body weight, visceral fat index (visceral fat/body weight), liver index (liver/body weight), insulin resistance, portal lipopolysaccharide (LPS), serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and liver triglycerides were measured. The intestinal microbiota in the different groups of rats was sequenced using high-throughput sequencing technology.


RESULTS
The FFAT group had higher body weight, visceral fat index, liver index, peripheral insulin resistance, portal LPS, serum ALT, serum AST, and liver triglycerides compared with all other groups (P < 0.05). Taking the same calories, the RFAT and RSUG groups demonstrated increased body weight, visceral fat index, peripheral insulin resistance and liver triglycerides compared with the PRO group (P < 0.05). The RFAT group also showed increased portal LPS compared with the PRO group (P < 0.05). Unweighted UniFrac principal coordinates analysis of the sequencing data revealed that the intestinal microbiota structures of the CON, FFAT, RSUG and PRO groups were roughly separated away from each other. Taxon-based analysis showed that, compared with the CON group, the FFAT group had an increased abundance of Firmicutes, Roseburia and Oscillospira bacteria, a higher ratio of Firmicutes to Bacteroidetes, and a decreased abundance of Bacteroidetes, Bacteroides and Parabacteroides bacteria (P < 0.05). The RFAT group showed an increased abundance of Firmicutes and decreased abundance of Parabacteroides bacteria (P < 0.05). The RSUG group showed an increased abundance of Bacteroidetes and Sutterella bacteria, higher ratio of Bacteroidetes to Firmicutes, and a decreased abundance of Firmicutes (P < 0.05). The PRO group showed an increased abundance of Bacteroidetes, Prevotella, Oscillospira and Sutterella bacteria, and a decreased abundance of Firmicutes (P < 0.05). Compared with the FFAT group, the RFAT group had an increased abundance of Bacteroidetes, higher ratio of Bacteroidetes to Firmicutes, and decreased abundance of Firmicutes and Oscillospira bacteria (P < 0.05).


CONCLUSIONS
Compared with the high-protein diet, the NAFLD-inducing effects of high-fat and high-sugar diets are independent from calories, and may be associated with changed intestinal microbiota.
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Jian-Ping
JP
Liu
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Wen-Li
WL
Zou
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Shui-Jiao
SJ
Chen
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Hong-Yun
HY
Wei
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Ya-Ni
YN
Yin
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Yi-You
YY
Zou
Jian-Ping Liu, Hong-Yun Wei, Fang-Gen Lu, Department of Gastroenterology, Second Xiangya Hospital of Central South University, Changsha 410011, Hunan Province, China.
Fang-Gen
FG
Lu
D000818:Animals; D004032:Diet / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects; D004044:Dietary Proteins / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D002149:Energy Intake; D000069196:Gastrointestinal Microbiome; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000378:metabolism / Q000382:microbiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004040:Dietary Carbohydrates; D004044:Dietary Proteins
High-fat diet; High-protein diet; Intestinal microbiota; Nonalcoholic fatty liver disease; Restrictive high-fat diet; Restrictive high-sugar diet