What is already known
Obesity has become a global health threat, with more than one billion people expected to be affected by it in 2030. Studies in animal models have revealed a link between the gut microbiota and body weight, but a causative relationship in humans remains unclear.
What this research adds
Researchers reviewed the scientific literature for evidence around the contribution of the gut microbiota to the development of obesity in humans. The team summarized findings from animal and human studies and provided an overview of approaches that target gut microbes to curtail obesity.
Conclusions
Although a causative relationship between obesity and gut microbes remains unclear, microbiota-based treatments may help to combat obesity.
Obesity has become a global health threat, with more than one billion people expected to be affected by it in 2030. But although a causative relationship between obesity and gut microbes remains unclear, microbiota-based treatments may help to combat obesity.
That’s the conclusion of a study that reviewed the scientific literature for evidence around the contribution of the gut microbiota to the development of obesity in humans.
Several studies in animal models have revealed a link between gut bacteria and body weight. In humans, scientists observed that infants who receive antibiotics in the first years of life as well as those delivered via C-section, who are seeded with skin microbes rather than gut and vaginal ones, are more often obese than children who do not receive antibiotics in early life or are born through a vaginal birth. “Although these observations are compelling, they provide only limited evidence supporting a causal role for the gut microbiome in the development of obesity,” the authors say.
The team, led by Douwe de Wit at the University of Amsterdam in the Netherlands, set out to summarize the findings from animal and human studies that have linked the microbiota to obesity and provide an overview of approaches that target gut microbes to curtail obesity.
Animal studies
Mouse studies have found a link between the gut microbiota and body weight, and they have shown that transferring gut microbes from lean humans to obese mice reduced obesity in mice. Animals treated with broad-spectrum antibiotics and given a high-fat diet showed weight gain, another study showed, and rodents quickly regained fat mass after dietary restriction as a result of an increased lipid absorption by Lactobacillus bacteria.
What’s more, animal studies suggest that the microbial metabolites short-chain fatty acids (SCFAs) are important for controlling satiety and food intake. But the extent to which SCFAs combat obesity is unclear. Similarly, there’s no evidence yet that other gut-derived metabolites such as bile acids can cause obesity, although these metabolites are involved in energy handling of the host.
“In summary, rodent studies unequivocally link the gut microbiome to energy handling and suggest a role of the gut microbiome in the development of obesity,” the researchers say. However, they add, differences in anatomy and microbiota composition between mice and humans may prevent some findings from being applicable to people.
Human trials
In humans, studies have linked early-life obesity to antibiotic use during pregnancy, and birth mode is known to influence an infant’s gut colonization. In obese people, scientists have consistently found altered expression of genes involved in metabolic function and decreased microbial diversity. However, an obesity-specific microbial or metabolic signature is still lacking.
Twin studies have identified several gut-derived metabolic pathways that appear to be enriched in obesity, but larger sample sizes are needed to validate these findings and elucidate the role of the different pathways.
Other studies in obese individuals showed that antibiotics do not have a major impact on energy handling, and it is unclear to what extent changes in microbiota composition influence weight loss or relapse after bariatric surgery — a surgical procedure used to manage obesity and obesity-related conditions.
Microbial-based therapies
Scientists have known that fecal microbiota transplants may alter the recipient’s gut microbiota composition, and trials have shown that microbiota transplants may help to induce weight loss in obese individuals in combination with bariatric surgery or a healthy diet. A clinical trial in China is ongoing to determine whether fecal microbiota transplants alone can reduce obesity.
Beneficial bacteria such as Lactobacillus and Bifidobacterium species, also known as probiotics, have also shown promise in curtailing obesity. For example, Akkermansia muciniphila can alter body weight in humans, though the mechanisms underlying this effect remain to be determined.
Prebiotics — organic compounds that promote the growth of beneficial bacteria — and postbiotics, which provide beneficial metabolites such as SCFAs and bile acids, may exert positive effects on weight regulation, too. However, larger studies are needed to clarify the role of pre- and post-biotics in reducing obesity.
Finally, bacteria such as Escherichia coli, Bifidobacterium and Lactobacillus species can be genetically engineered to produce favorable metabolites and pharmaceutical compounds. These genetically modified organisms, the authors say, “may have obesity-combatting benefits compared with classical probiotics through the possibility of specifically engineering desired effects combined with more profound insights into their mechanism of action.”
Future research into beneficial species, gut-derived metabolites and dietary components as well as their interactions with the human body may open the door to an era of microbiota-based therapies, the authors add. “In conclusion, although evidence to support a causal role for the gut microbiome in the development of obesity is insufficient, the gut microbiome’s involvement in human energy handling may be a valuable source of therapeutic entities in obesity.”
