Specific synbiotics in early life protect against diet‐induced obesity in adult mice

Abstract

AimsThe metabolic state of human adults is associated with their gut microbiome. The symbiosis between host and microbiome is initiated at birth, and early life microbiome perturbation can disturb health throughout life. Here, we determined how beneficial microbiome interventions in early life affect metabolic health in adulthood.MethodsPostnatal diets were supplemented with either prebiotics (scGOS/lcFOS) or synbiotics (scGOS/lcFOS with Bifidobacterium breve M‐16 V) until post‐natal (PN) day 42 in a well‐established rodent model for nutritional programming. Mice were subsequently challenged with a high‐fat Western‐style diet (WSD) for 8 weeks. Body weight and composition were monitored, as was gut microbiota composition at PN21, 42 and 98. Markers of glucose homeostasis, lipid metabolism and host transcriptomics of 6 target tissues were determined in adulthood (PN98).ResultsEarly life synbiotics protected mice against WSD‐induced excessive fat accumulation throughout life, replicable in 2 independent European animal facilities. Adult insulin sensitivity and dyslipidaemia were improved and most pronounced changes in gene expression were observed in the ileum. We observed subtle changes in faecal microbiota composition, both in early life and in adulthood, including increased abundance of Bifidobacterium. Microbiota transplantation using samples collected from synbiotics‐supplemented adolescent mice at PN42 to age‐matched germ‐free recipients did not transfer the beneficial phenotype, indicating that synbiotics‐modified microbiota at PN42 is not sufficient to transfer long‐lasting protection of metabolic health status.ConclusionTogether, these findings show the potential and importance of timing of synbiotic interventions in early life during crucial microbiota development as a preventive measure to lower the risk of obesity and improve metabolic health throughout life.

Supplementation of dietary non-digestible oligosaccharides from birth onwards improve social and reduce anxiety-like behaviour in male BALB/c mice

“…The modulatory effects of scGOS:lcFOS likely depends on the already resident mouse microbiota. This is supported by the findings in another mouse study, in which only the combination of scGOS:lcFOS with the probiotic Bifidobacterium breve M-16 V showed a bifidogenic effect in contrast to the intervention containing the prebiotic components only [49]. Possibly, the mice specific bifidobacterial species are inefficient in utilizing scGOS: lcFOS or are outcompeted by other bacterial species.…”

Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease

“…Pre-and pro-biotics and synbiotics are relatively inexpensive alternatives to conventional CVD medications, with fewer side effects (732). Mechanisms by which pre-and pro-bioticmediated changes in the gut microbiota may improve adipose function are still emerging, but may include the promotion of an anti-inflammatory milieu (including reducing intestinal permeability to decrease circulating endotoxins), enhancing fat oxidation, recruitment of beige adipocytes, increased energy expenditure, and improved lipoprotein profile, which collectively could improve insulin sensitivity and reduce ectopic fat to combat T2DM and CVD (733)(734)(735)(736)(737)(738)(739). While it is generally accepted that particular pre-and pro-biotics reduce diet-induced weight and adiposity gain in animal models (736,(740)(741)(742)(743), human intervention studies to date showing efficacy of probiotic treatment are still emerging (744,745), warranting further study (746).…”

Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT)

“…Breastmilk can be considered a synbiotic because it contains both probiotics, such as Bifidobacteria , and prebiotics, including galacto‐oligosaccharides (GOS) . Newborn mice supplemented with a synbiotic of GOS and Bifibacterium breve showed decreased body weight and improved insulin sensitivity and lipid profile while being fed an HFD‐diet throughout life . Breastfeeding is crucial in early childhood and continues to show beneficial effects for preventing childhood obesity .…”

“…41 Newborn mice supplemented with a synbiotic of GOS and Bifibacterium breve showed decreased body weight and improved insulin sensitivity and lipid profile while being fed an HFD-diet throughout life. 31 Breastfeeding is crucial in early childhood and continues to show beneficial effects for preventing childhood obesity. 103 Breastfed infants exhibited different gut microbiota and SCFA concentrations compared to formula-fed infants.…”