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One-year supplementation with Lactobacillus reuteri ATCC PTA 6475 counteracts a degradation of gut microbiota in older women with low bone mineral density.
Li, P, Ji, B, Luo, H, Sundh, D, Lorentzon, M, Nielsen, J
NPJ biofilms and microbiomes. 2022;8(1):84
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Osteoporosis is a highly prevalent bone disease in the elderly population and is characterised by decreased bone mineral density, deteriorated bone microarchitecture, reduced bone strength and increased susceptibility to fragility fractures. Due to the lack of awareness about osteoporosis, there is the need to develop a novel and effective intervention for its prevention and treatment. The aim of this study was to gain mechanistic insight into the effect of Lactobacillus reuteri ATCC PTA 6475 on bone metabolism and identify factors important for a good response to the probiotic. This study was based on a placebo-controlled cohort trial where 68 elderly women had been randomised to supplementation with the probiotic strain L. reuteri ATCC PTA 6475 or placebo. For this secondary analysis, 20 out of the 68 elderly women with bone loss who supplemented with probiotic L. reuteri ATCC PTA 6475 were selected. Results showed that after one-year probiotic supplementation, there was decreased inflammation and significantly increased gene richness of the gut microbiota in the good responders, whereas there was altered microbial composition and function, including enrichment of E. coli and its biofilm formation in the poor responders. Authors conclude that L. reuteri ATCC PTA 6475 supplementation might promote bone formation by modulating the gut microbiota composition and function, which could be crucial for the development of novel osteoporosis treatments.
Abstract
Recent studies have shown that probiotic supplementation has beneficial effects on bone metabolism. In a randomized controlled trial (RCT) we demonstrated that supplementation of Lactobacillus reuteri ATCC PTA 6475 reduced bone loss in older women with low bone mineral density. To investigate the mechanisms underlying the effect of L. reuteri ATCC PTA 6475 on bone metabolism, 20 women with the highest changes (good responders) and the lowest changes (poor responders) in tibia total volumetric BMD after one-year supplementation were selected from our previous RCT. In the current study we characterized the gut microbiome composition and function as well as serum metabolome in good responders and poor responders to the probiotic treatment as a secondary analysis. Although there were no significant differences in the microbial composition at high taxonomic levels, gene richness of the gut microbiota was significantly higher (P < 0.01 by the Wilcoxon rank-sum test) and inflammatory state was improved (P < 0.05 by the Wilcoxon signed-rank test) in the good responders at the end of the 12-month daily supplementation. Moreover, detrimental changes including the enrichment of E. coli (adjusted P < 0.05 by DESeq2) and its biofilm formation (P < 0.05 by GSA) observed in the poor responders were alleviated in the good responders by the treatment. Our results indicate that L. reuteri ATCC PTA 6475 supplementation has the potential to prevent a deterioration of the gut microbiota and inflammatory status in elderly women with low bone mineral density, which might have beneficial effects on bone metabolism.
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Gut microbiota alterations associated with reduced bone mineral density in older adults.
Das, M, Cronin, O, Keohane, DM, Cormac, EM, Nugent, H, Nugent, M, Molloy, C, O'Toole, PW, Shanahan, F, Molloy, MG, et al
Rheumatology (Oxford, England). 2019;58(12):2295-2304
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Osteoporosis, characterised by reduced bone density or ‘brittle bones’ affects a significant number of individuals over the age of 50 worldwide. Contributing factors include calcium and vitamin D deficiency and the presence of other inflammatory conditions. The composition of gut bacteria, the gut microbiome, plays an important role in immune activity and changes in composition have been associated with other inflammatory conditions. This cohort study of 181 individuals at high risk of reduced bone density and fractures, aimed to determine whether different gut microbiota composition is associated with bone density. Dexa scans and faecal samples were used as part of the assessment and confounding factors of diet, BMI, supplementation and medication were included in the analysis. The authors of the study found 6 species of gut bacteria that were significantly altered in numbers in the groups with osteoporosis and osteopenia, after controlling for confounding factors, and suggest that they could be used as markers of disease risk or progression and as a therapeutic target. Nutrition Practitioners working with bone density can focus on supporting the gut microbiome as part of their nutrition protocols.
Abstract
OBJECTIVE To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. METHODS Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis of the 16S (V3-V4 region) amplicon dataset classified to the genus level was used to identify significantly differentially abundant taxa. Adjustments were made for potential confounding variables identified from the literature using several statistical models. RESULTS We identified six genera that were significantly altered in abundance in the osteoporosis or osteopenic groups compared with age- and gender-matched controls. A detailed study of microbiota associations with meta-data variables that included BMI, health status, diet and medication revealed that these meta-data explained 15-17% of the variance within the microbiota dataset. BMD measurements were significantly associated with alterations in the microbiota. After controlling for known biological confounders, five of the six taxa remained significant. Overall microbiota alpha diversity did not correlate to BMD in this study. CONCLUSION Reduced BMD in osteopenia and osteoporosis is associated with an altered microbiota. These alterations may be useful as biomarkers or therapeutic targets in individuals at high risk of reductions in BMD. These observations will lead to a better understanding of the relationship between the microbiota and bone homeostasis.