Probiotic use decreases intestinal inflammation and increases bone density in healthy male but not female mice

Abstract

Osteoporosis can result from intestinal inflammation, as is seen with inflammatory bowel disease. Probiotics, microorganisms that provide a health benefit to the host when ingested in adequate amounts, can have anti-inflammatory properties and are currently being examined to treat inflammatory bowel disease. Here, we examined if treating healthy male mice with Lactobacillus reuteri ATCC PTA 6475 (a candidate probiotic with anti-TNFα activity) could affect intestinal TNFα levels and enhance bone density. Adult male mice were given L. reuteri 6475 orally by gavage for 3 ×/week for 4 weeks. Examination of jejunal and ileal RNA profiles indicates that L. reuteri suppressed basal TNFα mRNA levels in the jejunum and ileum in male mice, but surprisingly not in female mice. Next, we examined bone responses. Micro-computed tomography demonstrated that L. reuteri 6475 treatment increased male trabecular bone parameters (mineral density, bone volume fraction, trabecular number, and trabecular thickness) in the distal femur metaphyseal region as well as in the lumbar vertebrae. Cortical bone parameters were unaffected. Dynamic and static histomorphometry and serum remodeling parameters indicate that L. reuteri ingestion increases osteoblast serum markers and dynamic measures of bone formation in male mice. In contrast to male mice, L. reuteri had no effect on bone parameters in female mice. Taken together our studies indicate that femoral and vertebral bone formation increases in response to oral probiotic use, leading to increased trabecular bone volume in male mice.

Effects of the gut microbiota on bone mass

“…In addition, this treatment suppressed the ovx-induced increase in bone marrow CD4 + T cells, supporting the notion that the GM modulates the immune status in bone, and thereby affects OCL-mediated bone resorption. In a separate study, oral administration of L. reuteri treatment was shown to decrease intestinal inflammation and increase trabecular bone mass in gonadal intact male mice [53]. Taken together, these studies suggest that treatment with probiotics has beneficial effects on the immune status in bone, which in turn results in attenuated bone resorption in both ovx female mice and intact male mice.…”

Immunomodulation of Monocytes by Probiotic and Selected Lactic Acid Bacteria

“…Furthermore, the genes cyclopropane fatty acid synthase (cfa) [43] and L. reuteri-specific immunoregulatory (rsiR) gene [44] have been implicated in the anti-inflammatory properties of L. reuteri 6475. In addition to these immunomodulatory properties in vitro, L. reuteri 6475 has also shown promising effects in animal studies [45][46][47].…”

Gut microbiota induce IGF-1 and promote bone formation and growth

“…Consistent with this, Sjogren et al found that bacterial colonization of young adult GF animals resulted in loss of trabecular bone mass and an increase in bone-resorbing osteoclasts (13). However, other studies have suggested that treatment with beneficial microbes modestly increases bone mineral density (21)(22)(23)(24)(25)(26) and protects against bone loss after sex steroid deficiency (27). Discrepant results in studies examining the effect of microbiota on bone may reflect differences in the composition of the resident microbiota, age of the animal at colonization and necropsy, mouse strain, and sex.…”