Altering gut microbes prevents obesity, but only with healthy diet
Changing the mix of gut bacteria in mice prevented those destined for obesity from gaining weight and fat or developing related metabolic problems linked to insulin resistance – but only if the mice ate a healthy diet – a new study from Washington University School of Medicine in St. Louis has found.
Researchers said the study, published on 6 September 2013 in the journal Science, showed the “intimate connection” between gut microbes and diet is a key factor in the path to obesity. They said this connection could the stage for development of next-generation probiotics that can be added to foods to treat or prevent the disease.
Researchers used identical and fraternal female human twin pairs, ranging in age from 21 to 32, in which one twin was obese and the other lean – a weight disparity that occurs in about 6 per cent of twins. Gut microbes (captured from fecal samples) from the twins’ guts were transferred into mice that had been raised in a previously microbe-free environment.
Researchers showed that by transplanting entire collections of human microbes into different groups of mice, they could mimic the body composition of each twin. Mice fed low-fat mouse food and given gut microbes from an obese twin gained weight and fat and took on the metabolic dysfunction of the donor, while mice given gut microbes from a lean twin stayed lean.
In a further set of experiments for the study, the twins’ microbes were again transplanted into germ-free mice. In this round, mice with microbes from a lean twin were put in cages with mice carrying microbes form an obese twin. Because mice naturally eat one another’s feces, the researchers said they were able to observe what happened when a mouse carrying a collection of gut microbes from an obese twin was housed with another mouse carrying gut microbes from the lean twin. The animals in this experiment were fed “healthy” or “unhealthy” human diets.
The researchers showed that weight gain, accumulation of fat and development of metabolic problems were only prevented in mice that had “obese” microbes if they ate healthy diets. The prevention of problems was associated with an invasion of a group of bacteria called Bacteroidetes from mice with “lean” microbes into the guts of mice with “obese” microbes. Bacteroidetes are efficient at harvesting calories and nutrients from food and have been associated with leanness.
When the animals were fed a typical “unhealthy” diet – high in saturated fat and low in fruits and vegetables – there was no colonisation of “lean” microbes into the guts of mice carrying microbes from an “obese” twin. These mice gained weight and fat and developed metabolic problems.
If the animals ate a healthy diet low in saturate fat and high in fruits and vegetables, microbes from the lean twin invaded the gut of the mouse with the obese twin’s microbes, preventing weight gain and the development of metabolic problems associated with insulin resistance. In humans, insulin resistance is associated with significant weight gain and typically is the first sign of metabolic problems that eventually can lead to diabetes.
“Eating a healthy diet encourages microbes associated with leanness to quickly become incorporated into the gut,” said Jeffrey I. Gordon, MD, senior author and Director of the Centre for Genome Sciences and Systems Biology at Washington University. “But a diet high in saturated fat and low in fruits and vegetables thwarts the invasion of microbes associated with leanness. This is important as we look to develop next-generation probiotics as a treatment for obesity,” he said.
Diverse gut bacteria makeup vital
In 2009, a study by Dr Gordon and his colleagues indicated that the collections of microbes in the guts of obese people lacked the “diversity and richness” of people who were lean. According to researchers, the 2009 finding has been confirmed by the latest research.
“We think the lack of diversity leaves open niches – or jobs, if you will – that can be filled by microbes associated with leanness,” Dr Gordon said. “Our results underscore the strong interactions between gut microbes and diet and help illustrate how unhealthy diets select against gut microbes associated with leanness,” he said.
Microbes can be grown in lab, good news for treatment development
Throughout their experiments, the researchers found they could transmit an individual’s body composition and associated metabolic dysfunction to the mice regardless of whether a donor’s gut microbes were grown in the laboratory or transferred from a fecal sample.
“That’s good news from a therapeutic standpoint because there’s intense interest in identifying microbes that could be used to treat diseases,” Dr Gordon said. “Ideally, you want to be able to grow these naturally occurring unmodified human gut microbes in a lab and test whether various combinations of these organisms, with or without specified diet ingredients, can treat and/or prevent disease,” he said.
The intestine is home to tens of trillions of microbes that help break down food and synthesise nutrients and vitamins from the diet. Earlier research has established that collections of gut microbes can vary substantially from person to person, even among identical twins. Researchers said this inherent variation has made difficult to know whether diseases are rooted in “sick” gut microbial communities, a person’s own genetic makeup, or both.