Treatment With Multi-Species Probiotics Changes the Functions, Not the Composition of Gut Microbiota in Postmenopausal Women With Obesity: A Randomized, Double-Blind, Placebo-Controlled Study.

Mariusz Kaczmarczyk,Monika Szulińska,Tomasz Kosciolek,Igor Łoniewski,Karolina Skonieczna-Żydecka,Matylda Kręgielska-Narożna,Paweł Bogdański,Valentyn Bezshapkin

doi:10.3389/fcimb.2022.815798

Abstract

Probiotics are known to regulate host metabolism. In randomized controlled trial we aimed to assess whether interventions with probiotic containing following strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Levilactobacillus brevis W63, Lacticaseibacillus casei W56, Ligilactobacillus salivarius W24, Lactococcus lactis W19, and Lactococcus lactis W58 affect gut microbiota to promote metabolic effects. By 16S rRNA sequencing we analyzed the fecal microbiota of 56 obese, postmenopausal women randomized into three groups: (1) probiotic dose 2.5 × 109 CFU/day (n = 18), (2) 1 × 1010 CFU/day (n = 18), or (3) placebo (n = 20). In the set of linear mixed-effects models, the interaction between pre- or post-treatment bacterial abundance and time on cardiometabolic parameters was significantly (FDR-adjusted) modified by type of intervention (26 and 19 three-way interactions for the pre-treatment and post-treatment abundance, respectively), indicating the modification of the bio-physiological role of microbiota by probiotics. For example, the unfavorable effects of Erysipelotrichi, Erysipelotrichales, and Erysipelotrichaceae on BMI might be reversed, but the beneficial effect of Betaproteobacteria on BMI was diminished by probiotic treatment. Proinflammatory effect of Bacteroidaceae was alleviated by probiotic administration. However, probiotics did not affect the microbiota composition, and none of the baseline microbiota-related features could predict therapeutic response as defined by cluster analysis. Conclusions: Probiotic intervention alters the influence of microbiota on biochemical, physiological and immunological parameters, but it does not affect diversity and taxonomic composition. Baseline microbiota is not a predictor of therapeutic response to a multispecies probiotic. Further multi-omic and mechanistic studies performed on the bigger cohort of patients are needed to elucidate the cardiometabolic effect of investigated probiotics in postmenopausal obesity.

Highlights

Cardiometabolic risk factors (CMRFs), including obesity, abnormal lipid profile hypertension, insulin resistance, and aberrant glycemic control, play a role in the pathogenesis of cardiovascular diseases (CVD), which is one of the leading causes of mortality
No serious adverse reactions in the participating postmenopausal women with obesity were reported following the consumption of the multispecies probiotic supplement throughout the study
We found no relevant shifts in the microbiota during the study (Supplementary Figure 2), we examined whether the probiotics could be involved in altering the effect of post-treatment bacterial abundance on parameter changes, that is, whether a three-way interaction by time by post-treatment abundance by intervention exists, after controlling for the pretreatment abundance

Summary

Introduction

Cardiometabolic risk factors (CMRFs), including obesity, abnormal lipid profile hypertension, insulin resistance, and aberrant glycemic control, play a role in the pathogenesis of cardiovascular diseases (CVD), which is one of the leading causes of mortality. Due to the high prevalence of CVD, effective and safe methods to reduce CMRFs are being sought. One such intervention includes probiotic administration, which may have beneficial effects on some CMRFs (Skonieczna-Żydecka et al, 2020). A study by Szulińska et al (2018b) showed favorable effects of the administration of multistrain probiotics (PB) on glucose metabolism, lipid profile, waist circumference, visceral fat, serum uric acid level, and lipopolysaccharide (LPS) concentration in obese, postmenopausal women. One hypothesis explaining mode of action of the investigated bacterial consortium is the modification of the gut microbiota composition, which counteracts the adverse changes associated with CVD risk. The microbiota after PB administration has not been analyzed in individuals suffering from metabolic disorders, and the results observed after the application of this bacterial consortium in other groups of patients are inconclusive (Chahwan et al, 2019; Horvath et al, 2020a)

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