Lactobacillus rhamnosus attenuates bone loss and maintains bone health by skewing Treg-Th17 cell balance in Ovx mice

• Authors: Leena Sapra, All India Institute of Medical Sciences (AIIMS); Hamid Y Dar, Emory University; Asha Bhardwaj, All India Institute of Medical Sciences (AIIMS); Amit Pandey, All India Institute of Medical Sciences (AIIMS); Surbhi Kumari, All India Institute of Medical Sciences (AIIMS); Zaffar Azam, All India Institute of Medical Sciences (AIIMS); Vishu Upmanyu, All India Institute of Medical Sciences (AIIMS); Aleena Anwar, All India Institute of Medical Sciences (AIIMS); Prashant Shukla, Dr. Harisingh Gour Central University; Pradyumna K Mishra, ICMR-National Institute for Research in Environmental Health; Chaman Saini, All India Institute of Medical Sciences (AIIMS); Bhupendra Verma, All India Institute of Medical Sciences (AIIMS); Rupesh K Srivastava, All India Institute of Medical Sciences (AIIMS)
• Journal Title: SCIENTIFIC REPORTS
• Volume: Volume 11, Number 1
• Publisher: NATURE PORTFOLIO | 2021-01-19, Pages 1807-1807
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41598-020-80536-2
• Subjects: Environmental Sciences
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; T-CELLS; MICROBIOME; DIFFERENTIATION; HETEROGENEITY; OSTEOPOROSIS; FRACTURE

Abstract

Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4+Rorγt+Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4+Foxp3+Tregs and CD8+Foxp3+Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.