# Gut microbiome in early life and bone health outcomes at age 6: a Danish mother-child cohort study

## TL;DR

This study investigates how the gut microbiome in early life may influence bone health in children by age 6, using a large Danish mother-child cohort.

## Contribution

The study provides longitudinal insights into gut microbiome-bone health associations in early childhood using multiple analytical methods.

## Key findings

- Few associations were found between the early-life gut microbiome and bone health outcomes at age 6.
- Lower alpha diversity at 4 years and Escherichia-Shigella abundance at 1 month were linked to reduced bone measures.
- Sutterella abundance at 1 year was associated with lower BMD and BMC at 6 years.

## Abstract

The gut microbiome is associated with bone mass acquisition, yet evidence in childhood remains limited. Given that lower peak bone mass predicts osteoporosis in later life, understanding early influences is important. This analysis explores the association between the early life gut microbiome and bone health in later childhood. Data were obtained from 700 children recruited in pregnancy and followed prospectively within the Copenhagen Prospective Studies on Asthma in Childhood2010 cohort, a population-based mother-child cohort. The infant gut microbiome was measured at 1 wk (n = 445), 1 mo (n = 492), 1 yr (n = 508), 4 yr (n = 350), and 6 yr (n = 327) of age by 16S ribosomal ribonucleic acid amplicon sequencing targeting the fourth variable region. Total body less head BMD and area-adjusted BMC were measured by DXA at 6 yr of age. Associations were investigated by multiple linear regression, permutational analysis of variance, differential abundance analysis, and Random Forest machine learning. There were few associations between the early-life gut microbiome and bone health outcomes at age 6. We found negative associations between alpha (within-sample) diversity and area-adjusted BMC at 4 yr. Beta (between-sample) diversity of the gut microbiome at 6 yr was associated with concurrent BMD. Escherichia-Shigella abundance at 1 mo of age was associated with lower BMD. Sutterella abundance at 1 yr was associated with lower BMD and area-adjusted BMC at 6 yr. There were no other associations between the gut microbiome and bone outcome measures at any time point. In a well-powered unselected cohort study with longitudinal sampling of the gut microbiome, there were some suggestive but no consistent associations between the early gut microbiome and bone health outcomes at 6 yr of age.

Graphical Abstract