Microbiota Reconstitution Does Not Cause Bone Loss in Germ-Free Mice

Abstract

The microbiota has been shown to be an important regulator of health and development. With regard to its effect on bone health, a previous study has suggested that gut microbes negatively impact bone density. However, we show here that this is not generalizable to all microbial communities and mouse strain backgrounds. Our results demonstrate that colonization of mice, both outbred and inbred strains, did not have a major impact on bone health. The identification of microbial communities that do not negatively impact bone health may provide a foundation for future investigations that seek to identify microbes that are either beneficial or detrimental to bone metabolism.

Probiotic Lactobacillus reuteri Prevents Postantibiotic Bone Loss by Reducing Intestinal Dysbiosis and Preventing Barrier Disruption

“…Our studies show that the microbiota depletion seen at the 2‐week time point of antibiotic treatment did not affect bone density measures. Our results are similar to some germ‐free mouse studies . Studies in germ‐free mice, however, are inconsistent in terms of bone growth and density (increase, decrease, no change) .…”

“…Antibiotics save countless lives and can prevent the spread of pathogenic bacteria; however, a significant side‐effect of antibiotics is that they also deplete the commensal microbiota . Increasing numbers of studies demonstrate a role for the intestinal bacteria, as well as its composition in the regulation bone health . In the present study, we found that repopulation of the microbiota following acute antibiotic treatment results in dysbiosis, increases intestinal permeability, and has a detrimental effect on trabecular bone health.…”

“…DNA for microbial sequence analysis was extracted from mouse fecal samples by beadbeating and modified extraction with QIAGEN DNeasy Blood and Tissue Kits as described previously . Bacterial 16S sequences spanning variable region V4 were amplified by PCR with primers F515/R806 with a dual indexing approach and sequenced by Illumina MiSeq (Illumina, San Diego, CA, USA) as described previously .…”

“…Sequence data were processed using the MiSeq pipeline for mothur using software version 1.38.1 as described previously . In brief, forward and reverse reads were aligned, sequences were quality trimmed and aligned to the Silva 16S rRNA gene reference database formatted for mothur, and chimeric sequences were identified and removed using the mothur implementation of UCHIME.…”

“…In contrast, treatment with beneficial bacteria (probiotics) enhances bone density in healthy male mice, ovariectomized female mice, inflamed intact female mice, and type 1 diabetic male mice . Although earlier studies in germ‐free mice suggested a negative role for normal microbiota in bone health, subsequent findings have been inconsistent . This may be because of several factors, including differences in the composition of the microbiota used to conventionalize germ‐free mice.…”