Could early life synbiotics help protect against obesity later in life?

By Tim Cutcliffe

- Last updated on GMT

Picture credit: © Nutricia Research
Picture credit: © Nutricia Research
A combination of pro- and prebiotics (synbiotics) protected mice against the obesity-inducing effects of a Western diet, new research shows.

Young mice supplemented with synbiotics for the first 6 weeks of life showed reduced fat mass and body weight when faced with a subsequent 8-week Western style Diet (WSD) challenge, found the researchers.

The team was a collaboration between, the Universities of Gothenburg, Copenhagen and Wageningen, together with Nutricia Research, Netherlands. The work was funded by Nutricia Research.

Reduced measures of obesity in the synbiotic-supplemented group (SYN) were apparent at 10 and 14 weeks after birth, said the team writing in Diabetes, Obesity and Metabolism​.

No effect was reported either in mice supplemented with solely prebiotics, or in the control group. The findings were later replicated in a different animal facility in another European country.

The synbiotics also induced improvements in metabolic health parameters compared with controls. This included lower insulin levels, reduced liver weight and lower liver triglycerides.

Additionally, the scientists found that the synbiotics not only reduced total cholesterol levels in the SYN group, but also altered cholesterol metabolism in the ileum of adult mice.

The researchers examined 31 genes relating to biosynthesis, esterification, transport, distribution and regulation of cholesterol. Compared with controls, the analysis revealed significant changes in the expression of six cholesterol-related genes in the SYN group, with similar trends in numerous other genes.

“Early 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,” ​commented Professor Jan Knol, R&D Director at Nutricia Danone Research, Netherlands, also from the Laboratory of Microbiology, Wageningen University.

Changed microbiota

The synbiotic intervention consisted of a combination of short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides and Bifidobacterium breve M-16 V.

The synbiotics produced changes in the microbiome composition of the mice.  Higher levels of the beneficial bacterium Bifidobacterium ​were seen as early as 3 weeks of age, and were still evident at 14 weeks. The adult mice from the SYN group also had significantly lower levels of Bacteroidetes.

“We observed subtle changes in faecal microbiota composition, both in early life and in adulthood, including increased abundance of Bifidobacterium,”​ said Knol.

Microbiota transplant ineffective

In order to see whether a faecal matter transplant would protect recipient mice from the adverse effects of the WSD challenge, the researchers transferred microbiota from SYN and control group mice into 6-week old germ-free (GF) animals.

In this case, no protective effect was seen in the recipients of the SYN group microbiota. The scientists nevertheless speculated that an earlier transplant might have had a different effect.  

“We showed with our transplant experiment that transferring the synbiotics-modified microbial community from adolescent donors (at post-natal day 42 (PN42)) to age-matched GF mice does not confer protection against diet-induced obesity in recipients,”​ observed Knol.

“This implicates the importance of the timing of microbiota modulation; that is, exposure to synbiotics in early life is relevant for achieving long-lasting beneficial and protective metabolic effects.

“Provided that the gut microbiota differed between P21 and P42, we cannot exclude that the microbiota transplant from PN21 donors might have produced a different result,”​ Knol hypothesised.

Health implications

The importance of abundant levels of Bifidobacterium ​for gut and metabolic health is becoming increasingly recognised, suggested the scientists. Findings from this study add to this evidence, they argued.

Further replication in human studies is necessary. Nevertheless, the results could pave the way for early life interventions using synbiotics to help protect against obesity and metabolic disease in adulthood. Such interventions could play a major role in combatting the global obesity epidemic, proposed the scientists.

“This study adds evidence that early colonisation of the digestive tract by symbiotic microbes may be critical for healthy metabolic development, and maintenance of a healthy metabolism in adulthood.

“Obesity in adults and children is on the rise globally and there is no powerful cure, other than bariatric surgery, for this worldwide epidemic and its associated metabolic impairments. Our study provides important insights into the beneficial effects of supplementation with synbiotics in early life, which may lead to the development of preventive strategies; however, validation in humans is warranted,” ​concluded Knol.

Source:  Diabetes, Obesity and Metabolism

Published online ahead of print.  DOI:  10.1111/dom.13240

“Specific synbiotics in early life protect against diet-induced obesity in adult mice”

Authors:  Mona Mischke, Jan Knol et al

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