The global prevalence of overweight and obesity has nearly tripled in the past 50 years, and 40% of adults have overweight. The tools used to combat obesity include lifestyle changes, medication and surgery, but others think that probiotics will restore the gut’s natural balance. However, a new study shows that the effects of probiotics on obesity are difficult to predict. Using two different unhealthy diets, the researchers showed that the efficacy of two closely related probiotic lactic acid bacteria strains depended on the diet, with opposite effects with these two diets.
Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus and more.
Probiotics include many types of bacteria, and evidence so far suggests that taking them strengthens people’s health in many ways. However, the evidence from clinical trials is inconsistent and often of low quality. A new study helps to explain this.
“Whether methodological, genetic or environmental factors cause the lack of consistent results in previous studies remains largely unknown. We therefore investigated how various probiotics affect obesity with both low-fat and two high-fat diets. The two high-fat diets had vastly different effects, even with the same type of probiotics. The evidence suggests that specific probiotics should be complemented by a specific diet,” explains Benjamin A.H. Jensen, Associate Professor, Department of Biomedical Sciences, University of Copenhagen.
Classic high-fat or fast food–mimicking diet
Probiotics are live microorganisms that are supposed to improve people’s health when taken in appropriate amounts. The research into which microorganisms and which quantities are appropriate has been intense, especially because some clinical trials have shown promising clinical potential to reduce obesity, insulin resistance and nonalchoholic fatty liver disease.
“However, we were surprised that quite a few studies showed that suggested probiotics were not just ineffective but actually seemed to have negative effects in specific settings. We focus on biological context in our laboratory work. Successful treatment therefore requires improving the understanding of the precise abilities of specific bacteria in a given situation. Since bacteria are very promiscuous and adaptable, our theory is that probiotics must be followed up with a specific diet that fits the chosen treatment,” says Benjamin A.H. Jensen.
To support their hypothesis, the researchers carried out a systematic trial feeding mice for 12 weeks a low-fat reference diet or either a commonly used high-fat diet or a customised fast food–mimicking diet. In addition, the mice were given a daily supplement of one of two closely related but different probiotic strains of Lactobacillus bacteria – Limosilactobacillus reuteri or Lacticaseibacillus paracasei – or a placebo (water).
“The two probiotics had consistent and reproducible effects that differed with the two high-fat diets. L. paracasei prevented weight gain, improved insulin sensitivity and protected against the development of nonalcoholic fatty liver disease in the mice fed the classic high-fat diet but not the fast food–mimicking diet. Conversely, L. reuteri only had an effect with the fast food–mimicking diet by improving glucose control and mitigating the development of nonalcoholic fatty liver disease. These preclinical findings in mice align with similar observations from a randomised controlled trial involving humans published in the same issue of Gut Microbes as our controlled preclinical mouse study,” explains Benjamin A.H. Jensen.
Uncertain how diet changes the effect
This is the first investigation of how effective probiotics are when accompanied by two different high-fat diets that are equal in total energy, and the results emphasise that considering the total energy in the diet is not sufficient and that the composition of the diet is crucial.
“Our study shows that the response to probiotics depended on which diet the mice were fed. It also explains why previous studies have provided apparently contradictory results because of differences in the energy and fibre content of the diets. The new results are therefore important benchmarks for interpreting future results correctly,” says Benjamin A.H. Jensen.
Although what causes the effectiveness of probiotics to depend on diet remains uncertain, one explanation may be that different strains of bacteria require specific nutrients. The new results therefore emphasise the need to consider the effect of diet – when planning clinical trials but probably also ultimately when helping people become healthier and trying to help people with obesity and cardiometabolic diseases.
“Obesity is a leading risk factor for cardiometabolic multimorbidity. Although lifestyle interventions such as dietary restrictions may facilitate acute weight loss, they tend to gradually lose effectiveness. It is therefore important to have several alternatives to medication for treating obesity, including surgical strategies such as gastric bypass that are more successful but also highly invasive. Probiotics may prove to be an important tool for maintaining lifestyle-induced weight loss, since we now hopefully have begun to understand them better,” concludes Benjamin A.H. Jensen.