Caloric restriction disrupts gut microbiota, study says

CDC/Janice Carr

A very low calorie diet significantly alters the composition of the microbiota present in the human gut, according to new research from Charité Universitätsmedizin Berlin and the University of California in San Francisco published in the journal Nature.

In the study, the researchers report that dieting results in an increase of specific bacteria, notably Clostridioides difficile, which is associated with antibiotic-induced diarrhea and colitis. These bacteria apparently affect the body's energy balance by exerting an influence on the absorption of nutrients from the gut.

The human gut microbiome consists of trillions of microorganisms and differs from one person to the next. In persons who are overweight or obese, for instance, its composition is known to be different to that found in individuals with a normal body weight, the researchers said, though little is known about the effect dieting or weight loss has.

To explore the effects of dieting, the team studied 80 older post-menopausal women whose weight ranged from slightly overweight to severely obese for a duration of 16 weeks. The women either followed a medically supervised meal replacement regime, consuming shakes totaling less than 800 calories a day, or maintained their weight for the duration of the study.

The participants were examined at the Experimental and Clinical Research Center, a facility jointly operated by Charité and the Max Delbrück Center for Molecular Medicine. Regular stool sample analysis showed that dieting reduced the number of microorganisms present in the gut and changed the composition of the gut microbiome. 

Stool samples, which had been collected before and after dieting, were then transferred into mice, which had been kept under germ-free conditions and, as a result, lacked all gut microbiota. They found animals that received post-dieting stools lost more than 10 percent of their body mass. Pre-diet stools had no effect whatsoever. 

When the researchers studied stool composition in greater detail, they said they were particularly struck by signs of increased colonization by Clostridioides difficile. While this microorganism is commonly found in the natural environment and in the guts of healthy human beings and animals, its numbers in the gut can increase in response to antibiotic use, potentially resulting in severe inflammation of the gut wall. It is also known as one of the most common hospital-associated pathogens. Increased quantities of the bacterium were found both in participants who had completed the weight loss regimen and in mice which had received post-dieting gut bacteria.

The researchers concluded a very low-calorie diet severely modifies the gut microbiome and appears to reduce the colonization-resistance for the hospital-associated bacterium Clostridioides difficile. These changes render the absorption of nutrients across the gut wall less efficient, notably without producing relevant clinical symptoms. Further research is needed to determine the extent this type of asymptomatic colonization by Clostridioides difficile might impair or potentially improve a person's health, they said.

The researchers also said the study might give rise to treatment options for metabolic disorders such as obesity and diabetes. The researchers said they will now explore how gut bacteria might be influenced to produce beneficial effects on the weight and metabolism of their human hosts.