Digestion Speed The Latest Clue In Quest Against Obesity
By Deborah Borfitz
January 19, 2023 | The time it takes food to travel from the mouth to the rectum may change the metabolism of microbes in the gut. That’s one of the intriguing possibilities raised by a stool energy density study on overweight Danes recently completed by researchers at the University of Copenhagen, reports Henrik Roager, associate professor in the department of nutrition, exercise and sports.
The new study intended to estimate the efficiency of gut microbes at extracting energy from food, he says. It used preserved samples and anonymized data from 85 participants between 22 and 66 years of age initially enrolled in two unrelated dietary intervention trials conducted nearly a decade ago. The composition of gut microbes for each participant was also mapped.
As detailed in a recently published article in Microbiome (DOI: 10.1186/s40168-022-01418-5), about 40% of the study population had a so-called B-type composition of gut microbes dominated by Bacteroides bacteria that has been repeatedly associated with a Western lifestyle low in microbiota-accessible carbohydrates. The Bacteroides enterotype (B-type) was found, on average, to extract more energy from food than those with a Prevotella (P-type), strongly linked to a carbohydrate-rich diet and loose stools, or a Ruminococcaceae enterotype (R-type), correlated with the intake of animal proteins and fats and harder stools.
The B-type individuals also had the shorter intestinal transit times and were roughly 10% heavier (an extra nine kilograms on average) than their counterparts despite no observable differences in their eating habits over a four-day period, says Roager. This contradicted the expectation that those with the longer digestive travel times would be the ones who harvested the most nutrients from their food.
The effectiveness of the B-types in extracting energy from food may result in more calories being available from the same amount of food, but that they weighed more was just an observation, Roager stresses. Much work remains to be done to understand the underlying causal mechanism of the added pounds, which might involve differences in calorie absorption as well.
The research team is planning to design a validation study that could potentially also investigate if transplanting feces with variably low and high energy reserves into germ-free mice results in differing weight gain in the animals over time, adds Roager. This approach is reminiscent of older studies that launched the microbiome research field, only the donors would be selected based not on their body size but the relative efficiency of their microbiome at extracting energy.
It would be ideal, but not feasible currently, to collect gut microbiota from different parts of the gastrointestinal tract, Roager says. Not only do the physiological characteristics differ throughout the gastrointestinal sites (e.g, esophagus, stomach, and large and small intestines), but the microbes and their metabolism are site-specific.
New Health Frontier
Beyond early experiments conducted by modern-day microbiome researchers, few studies have been done looking at the microbiota compositions linked to energy extraction in humans, Roager says. Here, the motivation was to explore a possible link between energy extraction—as estimated by dry stool energy density—and specific microbiome compositions.
The microbiome has been a trending topic in the nutrition world over the past year, since it offers the potential to change the way multiple health conditions get managed, says Roager. But it remains a relatively new health frontier for the pharma industry possibly due to concerns that knowledge about the underlying mechanisms by which microbes affect health are still largely elusive and the regulatory environment is complicated.
Pharma companies certainly acknowledge the importance of happenings in the gut and that intestinal microbes could play a role in future commercial products, he adds. Recently, many companies have been most heavily focused on appetite hormones such as GLP-1, which can result in weight loss when combined with insulin (International Journal of Clinical Pharmacy, DOI: 10.1007/s11096-015-0219-8).
The U.S. Food and Drug Administration approved Rybelsus (semaglutide, Novo Nordisk), the first oral GLP-1 treatment for type 2 diabetes, in 2019. It was found to reduce both blood sugar level and body weight when added to insulin with or without metformin in patients with type 2 diabetes (Diabetes Care, DOI: 10.2337/dc19-0898).
Since gut microbes also regulate the secretion of appetite hormones, this could be an area of common interest between the nutrition and pharma industries, says Roager. Progress may depend on microbiologists working more closely with experts in gut physiology to better identify microbes and their signaling molecules in the gut and together learn how they interact with host cells and hunger hormones.
The work being done at the University of Copenhagen supports development of personalized nutrition and improved weight loss strategies, he continues, noting that intestinal transit time is an important but “largely neglected” factor shaping microbiome activity.
With long transit times, he explains, microbes tend to shift from fermenting fibers to fermenting proteins. Better understanding that phenomenon could have an impact on the amount of energy that gets extracted from the food.