Kefir Peptides Prevent Estrogen Deficiency-Induced Bone Loss and Modulate the Structure of the Gut Microbiota in Ovariectomized Mice

Abstract

Osteoporosis is a major skeletal disease associated with estrogen deficiency in postmenopausal women. Kefir-fermented peptides (KPs) are bioactive peptides with health-promoting benefits that are produced from the degradation of dairy milk proteins by the probiotic microflora in kefir grains. This study aimed to evaluate the effects of KPs on osteoporosis prevention and the modulation of the composition of the gut microbiota in ovariectomized (OVX) mice. OVX mice receiving an 8-week oral gavage of 100 mg of KPs and 100 mg of KPs + 10 mg Ca exhibited lower trabecular separation (Tb. Sp), and higher bone mineral density (BMD), trabecular number (Tb. N) and bone volume (BV/TV), than OVX groups receiving Ca alone and untreated mice, and these effects were also reflected in bones with better mechanical properties of strength and fracture toughness. The gut microbiota of the cecal contents was examined by 16S rDNA amplicon sequencing. α-Diversity analysis indicated that the gut microbiota of OVX mice was enriched more than that of sham mice, but the diversity was not changed significantly. Treatment with KPs caused increased microbiota richness and diversity in OVX mice compared with those in sham mice. The microbiota composition changed markedly in OVX mice compared with that in sham mice. Following the oral administration of KPs for 8 weeks, the abundances of Alloprevotella, Anaerostipes, Parasutterella, Romboutsia, Ruminococcus_1 and Streptococcus genera were restored to levels close to those in the sham group. However, the correlation of these bacterial populations with bone metabolism needs further investigation. Taken together, KPs prevent menopausal osteoporosis and mildly modulate the structure of the gut microbiota in OVX mice.

Bioactive Compounds from Kefir and Their Potential Benefits on Health: A Systematic Review and Meta‐Analysis

“…It is essential to highlight that the growth of butyrate-producing bacteria after estrogen deficiency in ovariectomized mice can negatively lead to a detrimental accumulation of SCFAs in the intestine. In contrast, bioactive peptides have not been able to restore the reduction in the Deferribacteres phylum caused by oophorectomy; the decrease of Deferribacteres is related to the detriment of vitamins and amino acid metabolism [ 80 ].…”

“…Thus, bioactive peptides can enrich beneficial bacteria and decreasing potentially harmful pathogens in the gut of ovariectomized females [ 80 ]. Still, these findings reveal that further studies, analyzing the relationship between intestinal microbiota and estrogen deficiency and the role of the bioactive peptides from kefir in this relationship, are necessary for a better understanding.…”

“…Concerning the richness and diversity of microbiota, interestingly, it is not affected by bioactive peptides in ovariectomized mice. However, peptides significantly improve intestinal microbiota diversity compared to control without ovariectomized procedure [ 80 ].…”

Milk and Dairy Products: Good or Bad for Human Bone? Practical Dietary Recommendations for the Prevention and Management of Osteoporosis

“…Additionally, animal bone had higher mechanical strength and fracture toughness. Additionally, differentiation of gut microbiota was higher in a group with kefir supplementation than placebo [ 95 ].…”

Suppression of Dendritic Cell Maturation by Kefir Peptides Alleviates Collagen-Induced Arthritis in Mice

“…Kefir starter grains purchased from Phermpep Co. (Taichung, Taiwan) were inoculated in sterilized fresh milk and incubated at 20°C for overnight to activate the grains. The grains were retrieved with a fine-mesh sieve, reinoculated into sterilized milk protein broth and incubated at the condition as previously described (Shi et al, 2018;Tu et al, 2020). The total peptide content in the KPs powder, calculated as the triglycine equivalent, was 23.1 g/100 g.…”