Intermittent Fasting Reshapes the Gut Microbiota and Metabolome and Reduces Weight Gain More Effectively Than Melatonin in Mice

Abstract

Background: Intermittent fasting (IF) can reduce energy intake and body weight (BW). Melatonin has many known functions, which include reducing appetite and preventing excessive weight gain.Objective: This study aimed to investigate the effects of IF on body fat and the gut microbiota and metabolome as well as a potential interaction with melatonin.Methods: Male C57BL/6J mice (23.0 ± 0.9 g, 6 wk old) were randomly assigned into four groups (12 mice/group): control (C), intermittent fasting (F), melatonin (M), and intermittent fasting plus melatonin (MF). The C and M groups mice were provided with ad libitum access to food and water, while the F and MF groups underwent alternative-day feed deprivation (15 cycles total). Melatonin was administered in the drinking water of the M and MF groups. Blood, epididymal fat, liver tissue, and intestinal tissue and contents were collected for lab measurements, histology, and microbiota and metabolome analysis. Main effects and interactions were tested by 2-factor ANOVA.Results: IF significantly reduced BW gain and serum glucose, total cholesterol (TC) and triglyceride (TG) levels. Adipocyte size significantly decreased with IF, then the number of adipocytes per square millimeter significantly increased (P < 0.05). Compared to the C group, the M and MF groups had significantly higher serum melatonin levels (17 and 21%, respectively), although melatonin monotherapy had no effect on serum parameters and adipocytes. There was no interaction between IF and melatonin on BW gain and serum parameters except for on adipocyte area and number per square millimeter, Bacteroidetes and Akkermansia bacterial abundance, and the levels of the intestinal metabolites alanine, valine and isoleucine. IF changed the intestinal microbiota structure, with the F and MF groups clearly separating from the C and M groups. Metabolomic analysis showed that there was obvious separation between all four groups.Conclusions: IF, but neither melatonin nor the interaction between IF and melatonin, could alter intestinal microbiota and metabolism and prevent obesity by reducing BW gain, serum glucose, TC, and TG, and adipocyte size in mice.

Fasting and refeeding triggers specific changes in bile acid profiles and gut microbiota

“…Consistent with the effects of sustained CR 42 , 43 and IF, 44 , 45 , 46 our study showed overnight fasting significantly increased α‐diversity of gut microbiota. Our results demonstrated that 24‐h fasting stimulated shifts in the abundance of several bacteria in feces, and these alterations were reversed upon refeeding.…”

“…In terms of the effect of diets on the abundance of Lactobacillus , previous studies have shown inconsistent results, with some studies suggesting that CR and IF interventions led to an increase in the abundance of Lactobacillus 42–45 and others showing that IF led to a decrease in the Lactobacillus 45 . Liu et al found that mice underwent IF (alternative‐day feed deprivation, 15 cycles total) had a significant increase in the abundance of Lactobacillus and Akkermansia compared with the control mice 44 . Zhang et al investigated the effects of three CR regimens (20% CR, 40% CR, and 60% CR) for 4 weeks on the gut microbiome composition in mice, and they found that CR dose‐dependently reduced the relative abundances of Bifidobacterium and remarkably increased the relative abundances of Lactobacillus and Akkermansia compared with the mice fed ad libitum 42 .…”

Effects of Ramadan and Non-ramadan Intermittent Fasting on Gut Microbiome

“…They found that IF compared to the control group led to a significant increase in the abundance of Lactobacillus , Ruminococcus , and Akkermansia strains. Also, they found a significant reduction in the abundance of Helicobacter , Prevotella , and Parasutterella in the IF group ( 14 ). In another study on farmed mink (Neovision vision), the gut microbiota load and diversity showed no change after 3 days of fasting.…”

Mechanisms of Melatonin in Obesity: A Review

“…Surprisingly, Liu et al recently proposed that intermittent fasting could reshape the intestinal microbiota and metabolome, reducing weight gain in mice more effectively than melatonin monotherapy. There was almost no interaction between intermittent fasting and melatonin except for the effect on the area and number of adipocyte area and number, the abundance of Bacteroides and Akkermansia, as well as the intestinal metabolites alanine, valine, and isoleucine [ 20 ]. Nevertheless, it still cannot deny the beneficial effects of melatonin in reshaping or improving the gut microbiota.…”