The Harvard Probiotics Symposium, “Gut health, microbiota & probiotics throughout the lifespan: Metabolic & brain function”, was held on September 15th and 16th at Harvard Medical School in Boston (USA).
The first day of the conference, moderated by Samuel Klein of Washington University School of Medicine (USA), was dedicated to the role of microbiota and probiotics in metabolic function—first in early life, and then in adulthood.
Speakers addressed some of the most pressing issues and questions in the field today:
What are humans’ earliest microbial exposures?
Physicians and researchers have long thought babies in the womb were sterile and that their first microbial exposures occurred during birth. At the symposium, Kjersti Aagaard of Baylor College of Medicine (USA) walked the audience through the growing evidence that microbial exposure starts before birth. Aagaard says her lab, and now seven others, have found evidence of culturable bacteria in the placenta. She noted that the placenta constitutes a microbially sparse habitat compared with other body sites—its bacterial load lies somewhere between a hot tub and the New York subway.
Aagaard showed data suggesting the microbiome of neonatal meconium varies according to the mother’s diet during gestation—namely, her fat intake. This connection underscores the importance of maintaining an appropriate diet and a healthy microbial community during pregnancy.
Josef Neu of University of Florida (USA) continued the theme of early microbial exposure by talking about microbes in the guts of infants who are breastfed. Neu mentioned the advantages of breastmilk for the developing infant and noted that a baby’s microbial dose from human milk is similar to the dose used in some probiotics studies. He predicted that in the future, mothers who cannot breastfeed may have access to more advanced products that approximate breastmilk: potentially beneficial microbes could be added to pasteurized donor milk, for example.
What is the current thinking on gut bacterial composition and obesity?
The importance of the Firmicutes to Bacteroidetes ratio in the gut microbiota of those with obesity has recently been a topic of debate. In the talk by Ronald Kahn of Harvard Medical School (USA), he argued gut microbiota differences between lean and obese individuals go beyond the Firmicutes to Bacteroidetes ratio, and include the metabolites produced by different groups of bacteria. Kahn underscored that, in mice, the gut microbiome appears to be an environmental factor that modifies aspects of obesity and metabolic syndrome, but that composition must be considered in combination with other factors that drive these conditions.
Rob Knight of University of California, San Diego (USA) covered the well-known mouse studies showing obesity can be transferred to germ-free mice through their gut microbiota. He described work showing that a few dozen bacterial species, working together, appear to influence weight.
Knight then asked an important question: even if we knew which bacterial composition would help a person slim down, how would we get the human gut microbiota to shift in that direction? So far scientists lack knowledge about how to manipulate the human microbiota to reliably induce a lean phenotype; in aiming for this, said Knight, next-generation probiotics will be instrumental. The challenge ahead is to develop a deeper understanding of ecological interactions among bacterial species and the dietary strategies that could help microbes establish in the gut.
The lecture by Patrice Cani of Université catholique de Louvain (Belgium) covered an important bacterial species associated with beneficial effects in obesity and diabetes: Akkermansia muciniphila. Cani mentioned different dietary components that, in some contexts, can change microbiota composition and increase levels of A. muciniphila: fish oils, omega 3, polyphenols, oligofructose, and inulin. He said the use of A. muciniphila as a next-generation probiotic is a desirable goal, but he also noted some challenges to address before this becomes a reality.
Eran Elinav of the Weizmann Institute of Science (Israel), highlighted in his talk the need to consider the personal nature of diet-microbiota interactions. His work in collaboration with Eran Segal showed that identical foods elicited drastically different blood glucose responses from person to person, and that gut microbes appeared to drive individuals’ personalized responses. Elinav said one day personalized dietary interventions, derived from microbiome data, may be used to influence health.
How is chronic inflammation implicated in metabolic syndrome?
Even if researchers knew for certain that changes in bacterial composition affected obesity, they would still need to know the involved mechanisms. In answer to this, Andrew Gewirtz of Georgia State University (USA) walked the audience through a possible chain of events leading to metabolic syndrome: when gut microbiome changes occur, they may affect the permeability of the gut barrier as well as food/bile acid metabolism and metabolite signaling; these could change metabolic regulation and chronic immune activation (inflammation), leading to metabolic syndrome.
What are the links between microbial diversity and health?
In keeping with previous research showing that gut microbiota diversity is generally associated with better health, Vincent Quagliarello of Yale University (USA) shared that older adults with low diversity gut microbiota are prone to large compositional changes that could negatively affect health.
Karine Clément of Pierre-and-Marie-Curie University (France) argued that, instead of thinking about diversity of bacterial species, researchers should focus on diversity of bacterial functions as encoded in their genes. Clément talked about research showing gut microbiome gene richness (low gene count vs. high gene count) appears to matter in obesity, and that a low gene count in the microbiota associates with increased risk factors for cardiometabolic disease.
Clément also said dietary pattern was associated with gut microbiota composition and gene richness; she and her colleagues found this gene richness could be modified through a short-term dietary intervention.
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