What is it about?
Food withdrawal is a lifestyle intervention that has been practiced in different regions of the world for millennia. It has been shown to have health benefits such as increased life span, disease prevention, and stress resistance. However, such lifestyle intervention is used without a unified standard and often produces contradictory outcomes. In order to evaluate the metabolic impact of food withdrawal on mammals, we conducted a comprehensive study using two groups of mouse models, one subjected to a normal diet and the other to high fat diet (HFD) intervention. In the study we investigated the changes in metabolic phenotypes, the compositions of intestinal microbiota, and the serum metabolomic profiles in response to a 4-day complete food withdrawal intervention. The results showed that food withdrawal decreased body weight, liver weight, and blood glucose levels. Intestinal microbiota and serum metabolome were impacted dramatically with the food withdrawal intervention especially in HFD groups. Beneficial bacterial species, such as Akkermansia muciniphila and Holdemania spp., were significantly elevated and certain metabolites that are positively associated to diabetes progression were decreased. Our results showed that food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and individuals' body fat percentage might be an important factor to be considered for food withdrawal.
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Why is it important?
Food withdrawal as a health enhancing measure has beneficial effects on aging, disease prevention and treatment. However, the cellular and molecular mechanisms involving gut microbial changes and metabolic consequences resulting from food withdrawal are yet to be elucidated. In this study, we subjected lean and obese mice to a dietary intervention that consisted of a four-day complete food withdrawal and eight-day 50% food withdrawal, and studied changes in caecal microbiome and host serum metabolome. The abundances of potentially pathogenic Proteobacteria were decreased and Akkermansia muciniphila was elevated by food withdrawal in HFD mice. Meanwhile, food withdrawal decreased abundance of metabolites in branched chain amino acid, lipid and free fatty acid metabolisms in host serum, more so in HFD mice than in normal mice. Microbial predicted function also showed that food withdrawal decreased the abundances of microbes associated with predicted diseases in the HFD group but not in the normal chow group. Correlation between the microbiome data and metabolomics data revealed strong association between gut microbial and host metabolic changes in response to food withdrawal. In summary, our results showed that food withdrawal was safer and more metabolically beneficial to HFD-induced obese mice than to normal lean mice, and the beneficial effects were primarily derived from the changes of gut microbiota, which closely associated with host metabolome.
Perspectives
There were several limitations in our study. (1) The experiment was designed to mimic the real-world situation when food withdrawal and dietary change most likely co-occur. The purpose of the experiment was to evaluate the collective effects of these lifestyle changes. We are cognizant that such experimental design did not allow us to tease apart the effects of caloric restriction from those of dietary change. In future studies, we will consider treating HFD mice with normal chow, with and without concurrent caloric restriction, to separate the effects of dietary change and caloric restriction. (2) Food withdrawal significantly decreased liver weight in HFD mice. We did not perform further analysis in the liver, and therefore what had changed in the liver and whether these changes contributed to metabolic improvement in the HFD mice remain unknown. (3) To further delineate the relationship between microbiome and metabolome, and their separate, additive, or synergistic effects on metabolic health, we will also consider use of germ free or commensal depleted animal models to study food withdrawal. (4) Human metabolic system is far more complex than that of mice, and therefore results generated from this mouse study only reflect food withdrawal-induced microbiota and metabolism alterations in mouse, not in human. Carefully designed clinical studies are required to reliably evaluate the effects of prolonged food withdrawal in people with different BMI, dietary habit, and metabolic health status.
Wei Jia
University of Hawaii Cancer Center
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This page is a summary of: Food withdrawal alters the gut microbiota and metabolome in mice, The FASEB Journal, September 2018, Federation of American Societies For Experimental Biology (FASEB),
DOI: 10.1096/fj.201700614r.
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