The bacteria found in some fermented dairy products, such as yogurt, may alter gene expression in human gut microbes, and resultant tweaks to metabolic processes could be behind gastrointestinal benefits often observed in people consuming such probiotic products, according to a study published today (26 October) in Science Translational Medicine. The work was funded by several grants from the National Institutes of Health and from Danone Research, the scientific research arm of Groupe Danone, a Paris-based multinational food products corporation that specializes in dairy products.
Since the 1990s, clinical trials have shown that probiotic bacteria can aid digestion in humans, but the molecular mechanisms involved in conferring those health benefits have proved difficult to pin down. "Nobody really understands how probiotics affect human health," said University of California, Davis, food microbiologist David Mills, who was not involved with the study. "What [this study] has shown is that maybe one of the mechanisms is by shifting the course of expression and how the microbes speak. Maybe that is part of the clue to how these types of foods are healthy."
Jeffrey Gordon, a microbiologist at Washington University in St. Louis, and his team gave a commercially-available probiotic yogurt containing five strains of bacteria to healthy adult volunteers and administered the same five strains to mice that harbored a subset of genetically-characterized human gut microbes. The yogurt bacteria did not significantly alter population structure in any of the entrenched gut microbes, in humans or mice—a result that is not surprising, according to Mills. "To assume that you could eat a yogurt and numerically challenge what's in your gut is kind of like dumping a gallon of Kool-Aid in your swimming pool and expecting it to change color," he said.
But RNA sequencing of the human gut microbes in the mice revealed that the probiotic bacteria changed the expression of gut microbe genes encoding key metabolic enzymes, such as those involved in the catabolism of sugars called xylooligosaccharides, which are found in many fruits and vegetables. Mass spectrometry of metabolites in urine, which result from the ramped up metabolic processes in the probiotic-fed mice, confirmed the alterations, and when the researchers ran similar analyses on gut microbes from the human yogurt eaters, they found upregulation of the same genes.
"The results show that in this particular set of conditions [probiotic] organisms are capable of altering the metabolic properties of a human microbial community," said Gordon.
The fact that Gordon's team could detect a signal of altered gene expression in the mice, which harbored only 15 species of human gut microbe, and that same signal was also apparent in the vastly more complex human gastrointestinal milieu is the start of something big, according to Gregor Reid, a nutritional researcher at the Lawson Health Research Institute in Canada who wasn't involved with the study. "Even with a very simplified model, they could replicate the effects they found in humans," said Reid, who wrote an accompanying opinion piece that was published in the same issue of Science Translational Medicine.
Gordon noted that the mouse model he used in the current study points a way forward to further probe the interactions between entrenched gut microbial communities and probiotic products, which could allow researchers to develop new hypotheses, identify novel biomarkers, and apply findings in preclinical models and eventually clinical uses for such products.
Continued research may also help to elucidate the precise interactions between probiotic bacteria or other dietary inputs and resident gut microbes that lead to alterations in gene expression and metabolism. "We don't know the nature of the molecular communications between these yogurt strains and the entrenched microbial community," Gordon said. "Each member of the [gut] community was able to adjust its metabolism presumably in a way that benefitted itself and the rest of the community as well. These organisms constantly try to find a niche or profession that allows them to survive in these complicated communities."
McNulty et al., "The Impact of a Consortium of Fermented Milk Strains on the Gut Microbiome of Gnotobiotic Mice and Monozygotic Twins," Science Translational Medicine, DOI: 10.1126/scitranslmed.3002701, 2011.