Supplementation with a probiotic was reported to alter gene expression by decreasing DNA methylation of 37 gene promoters related to obesity or weight-gain in mothers and 68 in children, said the team writing in the European Journal of Nutrition.
DNA methylation alters gene expression by adding a molecule known as a methyl group to DNA. The addition of this methyl group alters the activity level of the gene’s function through a mechanism known as transcription.
Levels of DNA methylation in several genes known to carry obesity risk, including the single most influential gene, were decreased in the probiotic-supplemented group, said the researchers from the University of Turku, Finland.
“Three of the known risk genes were affected specifically in the mothers and five in the children. The DNA methylation of the promoter of the fat mass and obesity-associated (FTO) gene, the strongest known genetic risk factor for obesity, was decreased in the women in response to the intake of the probiotics,” wrote lead researcher Professor Kirsi Laitinen.
The FTO has been linked with body mass index, obesity risk and type II diabetes in numerous studies, the researchers explained.
Significance
The finding that probiotics induced an epigenetic effect (probiotics given to the mother affected genes in the infant), may eventually provide novel strategies to combat obesity, the researchers suggest.
“Our present results suggest that probiotic supplementation during pregnancy may influence the DNA methylation of obesity and weight gain-related genes also in children,” wrote first author Sanna Vähämiko.
Genetics, together with environment, are both recognised to play a role in obesity, although the relative influence of each remains a matter of debate. Nevertheless, the findings of this study may in future be of relevance in families where obesity is prevalent.
“This highlights the question of whether probiotic supplementation during pregnancy and the resulting changes in DNA methylation and gene activity may evoke long-term health consequences in children,” suggested the scientists.
Study details
The small pilot study of 15 pregnant Finnish women was a double-blinded randomised controlled trial (RCT).
Seven women were randomised to receive one probiotic capsule per day containing Lactobacillus rhamnosus GG (American-type culture collection 53103, Valio Ltd, Helsinki, Finland) and Bifidobacterium lactis Bb12 (C. Hansen, Hoersholm, Denmark), 109 colony forming units/ day (cfu/d) each, while eight received placebo capsules. Dosing started on the first study visit during pregnancy and lasted until the end of exclusive breast-feeding, maximum 6 months.
The DNA methylation status of 623 obesity-related and 433 weight-gain-related gene promoters was evaluated from blood samples. The samples were taken from the mothers before supplementation commenced and between 6-12 months after the birth of their infants. (The scientists drew offspring at the same time). The researchers used a tool called Ingenuity Pathway to analyse the DNA methylation status.
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Future work
The researchers also observed effects of probiotics on the DNA methylation levels of genes involved with metabolic and immunological processes. Therefore, the use of probiotics in pregnancy may have other applications beyond just obesity, suggested the researchers.
However, significant further work is required to establish probiotics as a gene therapy tool.
The scientists stressed that collection of ribonucleic acid (RNA) was important to verify that DNA methylation changes actually translated into variations in gene expression. DNA methylation in tissues may also vary from that occurring in blood cells, they cautioned.
Since the trial size was extremely small, replication of results in larger studies is required, emphasised the researchers. Long-term follow-up assessments of the benefits of probiotics are also needed, as well as identification of which species/ strains are efficacious.
“Specific trials will be needed to clarify the effect of probiotics on the developmental programming of foetus and further on lifelong health effects in children, commented the researchers.
“Probiotics’ clinical effects are known to be dependent on which specific species and strains of probiotic are being used. Furthermore, we propose that each probiotic strain may have an independent effect on DNA methylation.
“The current findings are certainly encouraging; we hope that they will stimulate future investigations to verify these observations in primary tissues, in other populations and with other probiotic strains,” they concluded.
Source: European Journal of Nutrition
Published online, doi: 10.1007/s00394-017-1601-1
“The impact of probiotic supplementation during pregnancy on DNA methylation of obesity-related genes in mothers and their children”
Authors: Sanna Vähämiko, Asta Laiho, Riikka Lund, Erika Isolauri, Seppo Salminen, Kirsi Laitinen