The causal relationship between gut microbiota and bone mineral density: a Mendelian randomization study

Abstract

BackgroundThe gut microbiota has emerged as an intriguing and potentially influential factor in regulating bone health. However, the causal effect of the gut microbiota on bone mineral density (BMD) appears to differ throughout various life stages.MethodsWe conducted a Mendelian randomization (MR) analysis to investigate the potential causal relationship between gut microbiota and BMD in five distinct age groups: 0–15, 15–30, 30–45, 45–60, and 60 years and older. The analysis employed three different methods, namely MR-Egger, weighted median, and Inverse-variance weighting, to ensure the robustness of our findings, a series of sensitivity analyses were also conducted, such as horizontal pleiotropy tests, heterogeneity tests, and leave-one-out sensitivity tests.ResultsIn the age group of 0–15 years, Eubacterium_fissicatena_group and Eubacterium_hallii_group were identified as risk factors for BMD. During the 15–30 age group, Phascolarctobacterium, Roseburia, and Ruminococcaceae_UCG_003 were found to be protective factors for BMD. In the 30–45 age group, Lachnospira genus demonstrated a protective effect on BMD, while Barnesiella and Lactococcus were identified as risk factors for BMD. Moving on to the 45–60 age group, Eubacterium_ventriosum_group, Lachnospiraceae_UCG_004, and Subdoligranulum were observed to be protective factors for BMD, while Eubacterium_coprostanoligenes_group, Fusicatenibacter, and Lactococcus were associated with an increased risk of BMD. In individuals aged 60 years and older, Fusicatenibacter and Ruminococcaceae_UCG_002 were also noted as risk factors for BMD. Conversely, Eubacterium_ruminantium_group, Ruminococcus_gauvreauii_group, Alistipes, and Coprococcus_3 were found to be protective factors for BMD, whereas Barnesiella and Sellimonas were identified as risk factors for BMD.ConclusionA robust causal relationship between gut microbiota and bone mineral density (BMD) exists throughout all stages of life, with Firmicutes phylum being the primary group associated with BMD across age groups. Gut microbiota linked with BMD primarily belong to the Firmicutes phylum across age groups. The diversity of gut microbiota phyla associated with BMD depicts relatively stable patterns during the ages of 0–45 years. However, for individuals aged 45 years and above, there is an observed increase in the number of gut microbiota species linked with BMD, and by the age of 60 years, a trend toward an increase in the Bacteroidetes phylum categories is proposed.

Causal effects of gut microbiota in the development of lung cancer and its histological subtypes: A Mendelian randomization study

“…39 An MR analysis demonstrated that Eubacterium ruminantium group was negatively correlated with bone mineral density. 40 Moreover, our study revealed that this GM taxon was a protective factor for SCLC. Eubacterium ruminantium group possessed the ability to produce short-chain fatty acids that inhibit proinflammatory cytokines such as IFN-γ, IL-1β, IL-6, IL-8, and TNF-α, as well as increase the expression of anti-inflammatory cytokines, such as IL-10 and TGF-β, resulting in an overall anti-inflammatory effect.…”

A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose <span aria-describedby="tippy-24">Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats

“…This lower relative abundance of UCG-005 may be health-promoting given that UCG-005 is elevated in diabetes patients and is associated with elevated uric acid [72]. The genus Eubacterium_fissicatena_group was lower in prebiotic diet groups and is potentially harmful to bone mineral density [73] and correlates with obesity in a high-fat diet model [74]. Prebiotic diet also lowered Eubacterium_ruminantium_group, GCA-900066575, and Rikenellaceae_RC9_gut.…”

Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis

“…Alistipes is a gram-negative bacterium belonging to the phylum Bacteroidetes, and its main metabolites are succinic acid, acetic acid, and propionic acid ( Parker et al, 2020 ). An MR study on the causal relationship between the gut microbiota and bone mineral density (BMD) showed that Alistipes have a protective effect on BMD ( Wang et al, 2023 ). Furthermore, the relative abundance of Alistipes is decreased in osteoporosis patients ( Huang et al, 2022 ); however, we found that the expression abundance of Alistipes in OVX mice was significantly reduced, showing a strong positive correlation with gut barrier indicators, indicating that Alistipes may also be a potential mediator to regulate the microbiota-gut-bone axis.…”