Abnormal food timing and predisposition to weight gain: Role of barrier dysfunction and microbiota

Transl Res. 2021 May;231:113-123. doi: 10.1016/j.trsl.2020.11.007. Epub 2020 Nov 20.


Obesity has become a common rising health care problem, especially in "modern" societies. Obesity is considered a low-grade systemic inflammation, partly linked to leaky gut. Circadian rhythm disruption, a common habit in modern life, has been reported to cause gut barrier impairment. Abnormal time of eating, defined by eating close to or during rest time, is shown to cause circadian rhythm disruption. Here, using a non-obesogenic diet, we found that abnormal feeding time facilitated weight gain and induced metabolic dysregulation in mice. The effect of abnormal time of eating was associated with increased gut permeability, estimated by sucralose and/or lactulose ratio and disrupted intestinal barrier marker. Analysis of gut microbiota and their metabolites, as important regulators of barrier homeostasis, revealed that abnormal food timing reduced relative abundance of butyrate-producing bacteria, and the colonic butyrate level. Overall, our data supported that dysbiosis was characterized by increased intestinal permeability and decreased beneficial barrier butyrate-producing bacteria and/or metabolite to mechanistically link the time of eating to obesity. This data provides basis for noninvasive microbial-targeted interventions to improve intestinal barrier function as new opportunities for combating circadian rhythm disruption induced metabolic dysfunction.

MeSH terms

  • Animal Husbandry*
  • Animals
  • Biomarkers
  • Blood Glucose
  • Cadherins / metabolism
  • Circadian Rhythm*
  • Colon / metabolism
  • Food
  • Gastrointestinal Microbiome*
  • Glucose / metabolism
  • Insulin / blood
  • Insulin / metabolism
  • Leptin / blood
  • Leptin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism*
  • Random Allocation
  • Time Factors
  • Weight Gain*


  • Biomarkers
  • Blood Glucose
  • Cadherins
  • Insulin
  • Leptin
  • Glucose