A new study investigating how a low-calorie diet alters gut microbial populations is reporting unexpected results. The findings reveal a strange relationship between extreme caloric restriction and increased levels of a pathogenic bacteria linked to inflammatory bowel disease.
The research began by recruiting 80 overweight or obese subjects. Half the cohort were directed to maintain a stable weight for 16 weeks, while the other half completed a medically supervised weight-loss program including eight weeks of a very low calorie diet (800 kcal per day).
At the end of the study period the researchers took fecal samples from the participants and found those in the diet cohort showed substantial gut microbiome alterations, including generally reduced bacterial diversity. Reiner Jumpertz von Schwartzenberg, first author on the new study, says that alongside reducing the overall numbers of gut bacteria present, the dieting seemed to distinctly alter the behavior of the remaining microbes.
"We were able to observe how the bacteria adapted their metabolism in order to absorb more sugar molecules and, by doing so, make them unavailable to their human host,” he explains. “One might say we observed the development of a 'hungry microbiome’.”
Next, the researchers took fecal samples from the five subjects in the trial demonstrating the greatest weight loss and transplanted them into microbiome-free mice. Strikingly, the mice receiving the post-diet fecal transplants quickly lost about 10 percent of their total body mass, despite continuing to eat a regular diet. When mice were administered fecal transplants from the same human subjects before they started dieting no weight loss was detected whatsoever.
The final step in the research was to analyze the microbiomes of the human dieters in detail to try and home in on any specific microbial factor that could account for the weight loss. One particular bacterium quickly stood out: Clostridioides difficile (C. difficile).
Increased volumes of C. difficile have generally been associated with antibiotic use leading to gut inflammation. Severe diarrhea and colitis are often the end result of excessive C. difficile growth, however, none of these negative symptoms were detected in the dieting subjects.
“Ordinarily we would predict increased inflammation or even colitis following an increase in C. difficile,” says senior author Peter Turnbaugh.
Closer examination of the animals receiving the post-diet fecal transplants revealed very mild signs of inflammation, but nothing that would trigger negative colitis-like symptoms. Turnbaugh says this suggests C. difficile plays a metabolic role quite separate from the bacterium’s ability to drive gut inflammation.
... it is becoming increasingly clear there is no straightforward delineation between “good” and “bad” bacteria
It is unclear at this stage exactly how greater levels of C. difficile lead to weight loss without triggering gut inflammation. It is known C. difficile plays a role in fat metabolism and nutrient absorption through the gut wall. But Turnbaugh stresses these findings do not mean people should seek out C. difficile as some kind of weight loss probiotic.
“Let’s be clear; we are definitely not promoting C. difficile as a new weight loss strategy,” says Turnbaugh. “We’ve got a lot of biology left to unpack here.”
This new surprising study serves as another reminder of just how complex the relationship is between our health and microbiome. As scientists learn more it is becoming increasingly clear there is no straightforward delineation between “good” and “bad” bacteria.
Turnbaugh says further work will need to investigate whether these kinds of diet-induced C. difficile changes can lead to gut inflammation. And if they don’t inherently lead to harmful outcomes the million-dollar question is: Why?
“Multiple lines of research shows that the gut microbiome can either hinder or enhance weight loss,” Turnbaugh says. “We want to better understand how common weight loss diets might impact and the microbiome and what the downstream consequences are for health and disease.”
The new study was published in the journal Nature.
