Heyndrickxia coagulans Promotes Intestinal Calcium Absorption and Synergistically Ameliorates Bone Loss with Calcium Supplementation Efficacy and Mechanisms

Abstract Modulating the gut microbiota has emerged as a novel strategy to address global calcium deficiency and its associated skeletal disorders, overcoming the limited bioavailability of traditional supplements. This study evaluated the efficacy of the highly tolerant, spore-forming Heyndrickxia coagulans (H. coagulans) in promoting intestinal calcium absorption. After screening 51 wild-type isolates, the selected strains significantly activated the cellular calcium transport network in a Caco-2 cell monolayer model, as evidenced by upregulation of TRPV6, VDR, PMCA1B, and NCX1 (P < 0.05). In a low-calcium diet-induced murine model, co-supplementation of H. coagulans and calcium significantly restored serum calcium levels (P < 0.0001) and attenuated abnormal alkaline phosphatase (ALP) activity, decreasing from 225.97 U/L to 95.00 U/L (P < 0.0001). Furthermore, micro-computed tomography (micro-CT) showed that the combined intervention produced greater improvements in trabecular microarchitecture than calcium supplementation alone, with bone volume fraction (BV/TV) increasing from 9.83% to 19.50% (P < 0.001) and trabecular number (Tb.N) rising from 1.03 to 1.94 mm⁻¹. These findings highlight the potential of H. coagulans as a novel probiotic adjunct to calcium supplementation for enhancing mineral bioavailability and achieving greater amelioration of bone loss than calcium supplementation alone.