Components of the Gut Microbiome That Influence Bone Tissue-Level Strength

Abstract

Modifications to the constituents of the gut microbiome influence bone density and tissue-level strength, but the specific microbial components that influence tissue-level strength in bone are not known. Here, we selectively modify constituents of the gut microbiota using narrow-spectrum antibiotics to identify components of the microbiome associated with changes in bone mechanical and material properties. Male C57BL/6J mice (4 weeks) were divided into seven groups (n = 7-10/group) and had taxa within the gut microbiome removed through dosing with: (i) ampicillin; (ii) neomycin; (iii) vancomycin; (iv) metronidazole; (v) a cocktail of all four antibiotics together (with zero-calorie sweetener to ensure intake); (vi) zero-calorie sweetener only; or (vii) no additive (untreated) for 12 weeks. Individual antibiotics remove only some taxa from the gut, while the cocktail of all four removes almost all microbes. After accounting for differences in geometry, whole bone strength was reduced in animals with gut microbiome modified by neomycin (À28%, p = 0.002) and was increased in the group in which the gut microbiome was altered by sweetener alone (+39%, p < 0.001). Analysis of the fecal microbiota detected seven lower-ranked taxa differentially abundant in animals with impaired tissue-level strength and 14 differentially abundant taxa associated with increased tissue-level strength. Histological and serum markers of bone turnover and trabecular bone volume per tissue volume (BV/TV) did not differ among groups. These findings demonstrate that modifications to the taxonomic components of the gut microbiome have the potential to decrease or increase tissuelevel strength of bone independent of bone quantity and without noticeable changes in bone turnover.

Vitamin K in COVID-19—Potential Anti-COVID-19 Properties of Fermented Milk Fortified with Bee Honey as a Natural Source of Vitamin K and Probiotics

“…Vitamin K exists in a variety of food sources, signifying diet as a major source of vitamin K (predominately PK) [42]. Because of its multiple bioactivities, sufficient intake of vitamin K is considered a marker of a healthy diet and healthy gut [27].…”

“…In a sample of healthy young Japanese women, lower intake of vitamin k and iron was associated with a high relative abundance of Bacteroides and Clostridium and lower levels of healthpromoting bacteria (e.g., Bifidobacterium) [43]. From another perspective, the human gut microbiome is considered the main source of MK [42]. Nonetheless, among various human microbial species that synthesize vitamins, microbial species involved in MK biosynthesis are reported to have the lowest abundance [44].…”

“…Nonetheless, among various human microbial species that synthesize vitamins, microbial species involved in MK biosynthesis are reported to have the lowest abundance [44]. Because microbe-derived vitamin K is deficient in renal and age-related diseases (e.g., impaired bone strength and cognition) [42,45,46], it is reported that gut microbiome alteration in these conditions involves a reduction in MK-forming bacterial species in the gut, along with depleted levels of MK, especially longer chain isoforms, in the cecum, liver, kidney, and brain [42,45]. Thus, depleted production of gut-derived MK may be another reason for vitamin K deficiency in those groups when they contract COVID-19-research is needed to investigate such a possibility.…”

“…Gut invasion by SARS-CoV-2 may interfere with vitamin K absorption from the intestine [37,47]. It may also interfere with gut microbial structure resulting in diminution of nutrient-producing microbial species, which may lower the levels of gut-derived MK [38,39,42,45]. Deficiency of active vitamin K reduces cMGP and cOC, along with the accelerated accumulation of dp-ucMGP [10].…”

Evaluation of an Antibiotic Cocktail for Fecal Microbiota Transplantation in Mouse

“…The antibiotic cocktail containing vancomycin, ampicillin, neomycin, and metronidazole have been adopted widely in mice (10)(11)(12). Vancomycin belonging to glycopeptide antibiotics, ampicillin belonging to beta-lactam antibiotics, neomycin belonging to aminoglycoside antibiotics, and metronidazole belonging to nitroimidazoles antibiotics constitute the most common classes of antibiotics against gram-positive bacteria, aerobes or anaerobes (13).…”