“Our results show participant-specific effects of a probiotic supplement on improving parameters of metabolic syndrome and suggest that dietary factors may enhance stability and efficacy of the supplement,” wrote the team of researchers led by Dr. Justin Sonnenburg, professor of microbiology and immunology at Stanford University.
Published in the journal Gut Microbes, the study was supported by a sponsored research agreement with The Clorox Company, which entered the vitamins, minerals and supplements sector with the acquisition of RenewLife in 2016.
Probiotics and metabolic syndrome
Noting the established connection between the gut microbiome and an individual’s immune and metabolic status, as well as the promise of probiotics for host health, the researchers set out to evaluate the effects of a proprietary probiotic blend on elevated parameters of metabolic syndrome.
This blend contained three probiotic strains (Limosilactobacillus reuteri NCIMB 30242, Lactiplantibacillus plantarum UALp-05 and Bifidobacterium animalis subsp. lactis B420), each previously correlated with improved features of metabolic syndrome including glucose metabolism, weight loss and blood lipid profiles in clinical trial.
“Benefit from probiotic supplementation has been strongest for gut-specific diseases such as diarrhea, irritable bowel syndrome and Clostridioides difficile infection,” the researchers wrote. “The ability of probiotics to impact metabolic syndrome in human subjects has shown only modest benefits in clinical characteristics and inflammatory markers.”
The randomized, double-blind, placebo-controlled study recruited 39 adults with central obesity and other parameters of metabolic syndrome including elevated blood pressure, elevated fasting blood sugar, low HDL cholesterol and elevated triglycerides, or who were prescribed medication to control these conditions. Over the 10-week test period, participants either consumed one probiotic capsule (n=26) or a microcrystalline cellulose placebo (n=13) daily.
All participants provided blood and stool samples during the four weeks prior to the intervention (baseline), the 10-week intervention period and the 4-week washout period. Five participants in the probiotic group were excluded as they met only two of the three required parameters for metabolic syndrome as defined by the International Diabetes Foundation.
Analysis revealed that the probiotic did not have group-wide effects in metabolic syndrome or immune parameters but divided the probiotic group into what the research team termed probiotic responders and non-responders.
“While we did not see changes in metabolic syndrome markers in response to the probiotic across the entire cohort, there were significant improvements in triglycerides and diastolic blood pressure in a subset of probiotic arm participants,” the researchers noted. “Conversely, the non-responders had increased blood glucose and insulin levels over time.”
Responders and non-responders
To explain the variation in the effects of probiotic treatment, the study pointed to the distinct microbiome profile and increased beta diversity of responders at the end of the intervention compared to placebo and probiotic non-responders, with diet as a key differentiating factor between responders and non-responders.
“An analysis of participants’ diets revealed a difference in the consumption of certain nutrients such as sugars, lactose and folate, all of which were consumed in greater quantities in responders relative to non-responders throughout the study,” the researchers wrote.
While acknowledging that the effect of increased sugar consumption might be counter-intuitive given the link with poor metabolic health, the study suggests that “consumed sugars may have functioned as a prebiotic that in combination with the probiotic supplement could have produced a synbiotic effect.”
The Sonnenburg Lab also identified a change in homovanillic acid (HVA) – a metabolite of dopamine – as predictive of responder status with a fairly-high level of accuracy (71%), with HVA levels declining in non-responders over the study period.
In addition, Akkermansia muciniphila was enriched in the non-responders relative to responders. Several studies have linked the mucin-degrading bacterium with improved metabolic health, but a recent review highlights associations with poor glycemic control, colitis and pathogen-induced inflammation among other negative outcomes.
The study calls for investigation into how differences in Akkermansia or other taxa between groups mediate outcome and encourages further research into how baseline characteristics might inform a personalized approach to treating conditions like metabolic syndrome.