Objective  To examine the relationship between intestinal flora and bone mineral density among rural Han residents aged 55 – 65 years in Taizhou city, Jiangsu province for exploring novel approaches to osteoporosis prevention.

  Methods  Using cluster random sampling, we recruited 537 rural Han long term (≥ 20 years) residents aged 55 – 65 years in 3 villages with more compliant followees and high response rate in a cohort for multidisciplinary and multiple diseases research – the Taizhou Longitudinal Study. Questionnaire interview, physical examination, bone density measurement and stool specimen detection were carried out among the selected residents from March 2013 through October 2018. The residents were then assigned into one of the 3 groups with normal bone density, osteopenia and osteoporosis based on bone density measurement according to the diagnostic criteria of World Health Organization. Differences in intestinal flora among the 3 groups and the correlation between intestinal flora and bone density were analyzed.

  Results  Of all the participants, 38.55% (207), 44.51% (239), and 16.94% (91) were assessed with normal bone density, osteopenia, and osteoporosis, respectively. After adjusting for variables such as gender, age, body mass index (BMI), smoking and alcohol drinking, the results of partial correlation analysis showed that intake frequency of fresh vegetables (β = – 0.125), fresh fruits (β = – 0.101), meat (β = – 0.098) ) and yogurt (β = – 0.033) were reversely correlated significantly with bone mineral density grouping (all P < 0.05). Compared with those in the normal bone density group, the intestinal abundances of Clostridium, Blautia, Campylobacter, Escherichia, Streptococcus, Actinomyces, Shigella, Anaerostipes, Streptomyces and Atopobium were significantly decreased in both osteopenia and osteoporosis group; but the intestinal abundances of Corynebacterium, Veillonella and Brevundimonas increased in osteopenia and osteoporosis group (all P < 0.05). After adjusting for confound-ing factors such as gender, age, BMI, smoking, alcohol drinking, and intake frequency of fresh vegetable/fresh fruit/ meat/yogurt, the results of unconditional multivariate logistic regression analysis showed that the increased intestinal relative abundance of Escherichia (odds ratio OR = 0.992, 95% confidence interval 95% CI: 0.985 – 0.999), Shigella (OR = 0.984, 95% CI: 0.970 – 0.998), Blautia (OR = 0.959, 95% CI: 0.924 – 0.996) and Fusicatenibacter (OR = 0.980, 95% CI: 0.962 – 0.998) are protective factors for the occurrence of osteopenia in the residents; the intestinal relative abundance of Faecalibacterium (OR = 1.060, 95% CI: 1.006 – 1.118) is a risk factor for osteoporosis incidence, while that of Mogibacterium (OR = 0.865, 95% CI: 0.763 – 0.981) is a protective factor for osteoporosis incidence.

  Conclusion  In 55 – 65 years old rural Han residents, intestinal flora may associate with bone density; increased intestinal abundance of Escherichia , Shigella, Blautia, Fusicatenibacter, Faecalibacterium, and Mogibacterium could affect bone mineral density of the population.