Xiaoli Zhang1,2, Yunpeng Dong3, Guoying Sun1, Ahmed A Hasan2,4, Mei Tian1,5, Suimin Zeng1,5, Jing Li1, Shiyu Zeng1, Jun Ma1, Jian Li1,5, Berthold Hocher6,7,8,9. 1. Department of Basic Medicine, Hunan Normal University, School of Medicine, Changsha, China. 2. Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany. 3. Department of Otolaryngology Head and Neck Surgery, Institute of Otology, the Second Xiangya Hospital, Central South University, Changsha, China. 4. Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. 5. Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China. 6. Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany, berthold.hocher@medma.uni-heidelberg.de. 7. Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China, berthold.hocher@medma.uni-heidelberg.de. 8. LADR GmbH, MVZ Neuruppin, Neuruppin, Germany, berthold.hocher@medma.uni-heidelberg.de. 9. Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China, berthold.hocher@medma.uni-heidelberg.de.
Abstract
BACKGROUND/AIMS: Paternal exposure to adverse environmental conditions can act on offspring's phenotype and influence offspring's later life disease risk. Our study was designed to examine the effect of feeding male rats before mating a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on their offspring's (F2) liver function and gut microbiome composition. METHODS: Male F0 rats and male F1 rats were fed either control diet or HFSSD before mating. Liver function of F2 offspring was investigated, and their gut microbiome composition was analyzed by 16S rRNA gene sequencing in the F2 offspring of rats whose fathers and grandfathers were fed with control diet (CD) (F0CD+F1CD-F2 group) or HFSSD prior to mating (F0HD+F1HD-F2 group). RESULTS: F2 offspring had higher serum aspartate aminotransferase activity (female, p < 0.05 and male, p < 0.01 respectively) compared with control. Shannon indexes of gut microbiota indicated a significantly higher diversity in the female F0HD+F1HD-F2 as compared to F0CD+F1CD-F2 female offspring (p < 0.01). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria. There were significant differences in gut bacterial community composition at phyla and genus level between the F0CD+F1CD-F2 and F0HD+F1HD-F2. Furthermore, the variation in the relative abundance (percentage) of bacterial genus in the F2 offspring was associated with liver function alterations induced by a paternal pre-conceptional unhealthy diet. Male F0HD+F1HD-F2 offspring had higher serum cholesterol, high density lipoproteins as well as low density lipoproteins concentrations compared to the corresponding male control rats. CONCLUSION: Taken together, our findings suggested that a paternal pre-conceptional unhealthy diet predisposes the offspring to mild liver function alterations and alterations of gut microbiota in later life. Effects on lipids were sex-specific and only seen in male offspring.
BACKGROUND/AIMS: Paternal exposure to adverse environmental conditions can act on offspring's phenotype and influence offspring's later life disease risk. Our study was designed to examine the effect of feeding male rats before mating a high-fat, high-sucrose and high-salt diet (HFSSD) over two generations (F0 and F1) on their offspring's (F2) liver function and gut microbiome composition. METHODS: Male F0 rats and male F1 rats were fed either control diet or HFSSD before mating. Liver function of F2 offspring was investigated, and their gut microbiome composition was analyzed by 16S rRNA gene sequencing in the F2 offspring of rats whose fathers and grandfathers were fed with control diet (CD) (F0CD+F1CD-F2 group) or HFSSD prior to mating (F0HD+F1HD-F2 group). RESULTS: F2 offspring had higher serum aspartate aminotransferase activity (female, p < 0.05 and male, p < 0.01 respectively) compared with control. Shannon indexes of gut microbiota indicated a significantly higher diversity in the female F0HD+F1HD-F2 as compared to F0CD+F1CD-F2 female offspring (p < 0.01). The dominant phyla of all the groups were Bacteroidetes, Firmicutes and Proteobacteria. There were significant differences in gut bacterial community composition at phyla and genus level between the F0CD+F1CD-F2 and F0HD+F1HD-F2. Furthermore, the variation in the relative abundance (percentage) of bacterial genus in the F2 offspring was associated with liver function alterations induced by a paternal pre-conceptional unhealthy diet. Male F0HD+F1HD-F2 offspring had higher serum cholesterol, high density lipoproteins as well as low density lipoproteins concentrations compared to the corresponding male control rats. CONCLUSION: Taken together, our findings suggested that a paternal pre-conceptional unhealthy diet predisposes the offspring to mild liver function alterations and alterations of gut microbiota in later life. Effects on lipids were sex-specific and only seen in male offspring.
Authors: Amy G Huebschmann; Rachel R Huxley; Wendy M Kohrt; Philip Zeitler; Judith G Regensteiner; Jane E B Reusch Journal: Diabetologia Date: 2019-08-27 Impact factor: 10.122