How diet affects a person’s weight appears to be much more complex than previously thought due to the potential role the gut microbiome plays in nutrient absorption, energy production, inflammation and metabolism.

It’s now well known that diet greatly influences the gut microbiome, and more recently research has shed light on how the gut microbiome is altered in obese vs normal weight individuals.

For this reason, the research team from the University of San Francisco led by Peter Turnbaugh, PhD sought to explore how changes in the gut microbiome upon following a very low-calorie liquid diet (less than 800 calories per day) affect a person’s health beyond weight loss.

Turnbaugh and colleagues study recently published in Nature involves a human randomized intervention in 80 post-menopausal women who were overweight or obese and either followed a medically supervised weight loss program (8 weeks very low-calorie liquid diet followed by 4 weeks conventional low-calorie diet and 4 weeks of weight maintenance) or a control diet. The team then sequenced fecal samples from the participants before, during and after the diet intervention over a period of 16 weeks.

As expected, the liquid low calorie diet resulted in weight loss and metabolic changes for most patients. For example, participants receiving this diet showed a weight reduction of 14 kg and lower adiposity that was still present at week 16.

Beyond its benefits on metabolic health, the very low-calorie diet also caused a reduction in short chain fatty acid production and an increase in bacteria that feed off of glycans, which are a type of polysaccharide, that were present in the liquid low calorie diet.

The researchers further explored if the gut microbiota was responsible for the patients’ weight loss by transferring stool samples obtained from participants before and after 12 weeks of weight loss program into experimental mice that didn’t have a microbiome of their own. The mice lost weight and fat tissue like the human participants, despite the fact that they were not on a low-calorie diet suggesting that the donor gut microbiome likely played a major role in weight loss. The researchers believe the weight loss was caused by a shift in the gut microbiome that led to decreased dietary energy absorption. Surprisingly, Turnbaugh’s team discovered that weight loss was associated with higher levels of the pathogenic bacteria Clostridioides difficile, which is known to cause severe diarrhea and hospitalization.

Interestingly, although weight loss correlated with higher levels of C. difficile toxins, colonization of this pathogen did not cause high levels of inflammation, which it commonly does, suggesting that this bacterium may also play a role in altering metabolism.

Importantly, dietary intervention decreased total bile acid pools. Certain gut bacteria can convert bile into the metabolite secondary bile salts which inhibit the growth of C. difficile in the gut. The authors suggest that the decreased levels of bile salts in the gut do not allow to keep the growth of C. difficile under control.

In conclusion, although following a very low calorie diet may be effective way to lose weight quickly, long-term extreme calorie restriction may have lasting negative consequences for the gut microbiome and overall health.

Even though this study only analyzed the effects of one type of very low-calorie liquid preparations, it sheds light on the possible negative effects calorie restriction can have on the gut microbiota composition which could have other health implications down the road. Therefore, the long-term effects dietary interventions, such as severe calorie restriction, have on the gut microbiota composition and function should be considered in future studies in obese patients. 


Reference: von Schwartzenberg, R.J., Bisanz, J.E., Lyalina, S. et al. Caloric restriction disrupts the microbiota and colonization resistance. Nature 595, 272–277 (2021).