The abundance of gut bacterial families as an early marker of diet-induced metabolic shift: a study in young pre-obese rats and a hint to a potential prophylactic window

The occurrence of overweight-obesity in youth has increased globally, with growing evidence supporting the relevance of the gut microenvironment as a pathophysiological factor. The time preceding obesity consolidation is particularly relevant to therapeutic management; therefore, we evaluated gut microbiota and inflammatory features in submucosal neurons during a status of diet-induced dysmetabolism prior to obesity. Rats received high-fat (HF) diet (62% calories from fat) from postnatal day 30 (p30) onwards, reaching moderate obesity by p90. At p45, although not overweight, they showed increased fasting glycaemia; between p45-60 they displayed higher adiposity and liver lipid content than rats fed chow (14% calories from fat); however, inflammation-related peptides remained unchanged in colonic submucosal neurons. Next, we investigated the role of microbiota in HF diet-induced metabolic alterations associated with that pre-obese status: caecal microbiota taken from p60 HF-rats was transferred to healthy recipients (orally, p30-45). Controls received vehicle or heat-inactivated HF microbiota. Microbiota transplantation from pre-obese rats increased glycaemia in healthy receptors, compared to those given heat-inactivated material. Next, we broadly characterized bacterial families from HF and control rats (p30-90) using Illumina MiSeq platform to sequence DNA from caecal content. In HF rats, Tannerellaceae and Bacteroidaceae abundances increased early (p45), whereas Muribaculaceae and Lactobacillaceae abundances significantly decreased at p60 and p90, respectively. Pre-obese caecal microbiota induced an increase in glycaemia in healthy rats, possibly contributing to pathology. It may also be an early metabolic shift marker. Characterization at the genus level may provide novel markers for obesity risk, improving the chances for successful interventions.