Manipulation of feeding patterns in high fat diet fed rats improves microbiota composition dynamics, inflammation and gut-brain signaling.

ABSTRACT

Chronic consumption of high fat (HF) diets has been shown to increase meal size and meal frequency in rodents, resulting in overeating. Reducing meal frequency and establishing periods of fasting, independently of caloric intake, may improve obesity-associated metabolic disorders. Additionally, diet-driven changes in microbiota composition have been shown to play a critical role in the development and maintenance of metabolic disorders. In this study, we used a pair-feeding paradigm to reduce meal frequency and snacking episodes while maintaining overall intake and body weight in HF fed rats. We hypothesized that manipulation of feeding patterns would improve microbiota composition and metabolic outcomes. Male Wistar rats were placed in three groups consuming either a HF, low fat diet (LF, matched for sugar), or pair-fed HF diet for 7 weeks (n = 11-12/group). Pair-fed animals received the same amount of food consumed by the HF fed group once daily before dark onset (HF-PF). Rats underwent oral glucose tolerance and gut peptide cholecystokinin sensitivity tests. Bacterial DNA was extracted from the feces collected during both dark and light cycles and sequenced via Illumina MiSeq sequencing of the 16S V4 region. Our pair-feeding paradigm reduced meal numbers, especially small meals in the inactive phase, without changing total caloric intake. This shift in feeding patterns reduced relative abundances of obesity-associated bacteria and maintained circadian fluctuations in microbial abundances. These changes were associated with improved gastrointestinal (GI) function, reduced inflammation, and improved glucose tolerance and gut to brain signaling. We concluded from these data that targeting snacking may help improve metabolic outcomes, independently of energy content of the diet and hyperphagia.