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  1. Article ; Online: Commensal Microbiota Effects on Craniofacial Skeletal Growth and Morphology.

    Gerasco, Joy E / Hathaway-Schrader, Jessica D / Poulides, Nicole A / Carson, Matthew D / Okhura, Naoto / Westwater, Caroline / Hatch, Nan E / Novince, Chad M

    JBMR plus

    2023  Volume 7, Issue 8, Page(s) e10775

    Abstract: Microbes colonize anatomical sites in health to form commensal microbial communities (e.g., commensal gut microbiota, commensal skin microbiota, commensal oral microbiota). Commensal microbiota has indirect effects on host growth and maturation through ... ...

    Abstract Microbes colonize anatomical sites in health to form commensal microbial communities (e.g., commensal gut microbiota, commensal skin microbiota, commensal oral microbiota). Commensal microbiota has indirect effects on host growth and maturation through interactions with the host immune system. The commensal microbiota was recently introduced as a novel regulator of skeletal growth and morphology at noncraniofacial sites. Further, we and others have shown that commensal gut microbes, such as segmented filamentous bacteria (SFB), contribute to noncraniofacial skeletal growth and maturation. However, commensal microbiota effects on craniofacial skeletal growth and morphology are unclear. To determine the commensal microbiota's role in craniofacial skeletal growth and morphology, we performed craniometric and bone mineral density analyses on skulls from 9-week-old female C57BL/6T germ-free (GF) mice (no microbes), excluded-flora (EF) specific-pathogen-free mice (commensal microbiota), and murine-pathogen-free (MPF) specific-pathogen-free mice (commensal microbiota with SFB). Investigations comparing EF and GF mice revealed that commensal microbiota impacted the size and shape of the craniofacial skeleton. EF versus GF mice exhibited an elongated gross skull length. Cranial bone length analyses normalized to skull length showed that EF versus GF mice had enhanced frontal bone length and reduced cranial base length. The shortened cranial base in EF mice was attributed to decreased presphenoid, basisphenoid, and basioccipital bone lengths. Investigations comparing MPF mice and EF mice demonstrated that commensal gut microbes played a role in craniofacial skeletal morphology. Cranial bone length analyses normalized to skull length showed that MPF versus EF mice had reduced frontal bone length and increased cranial base length. The elongated cranial base in MPF mice was due to enhanced presphenoid bone length. This work, which introduces the commensal microbiota as a contributor to craniofacial skeletal growth, underscores that noninvasive interventions in the gut microbiome could potentially be employed to modify craniofacial skeletal morphology. © 2023 The Authors.
    Language English
    Publishing date 2023-05-31
    Publishing country England
    Document type Journal Article
    ISSN 2473-4039
    ISSN (online) 2473-4039
    DOI 10.1002/jbm4.10775
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Minocycline-induced disruption of the intestinal FXR/FGF15 axis impairs osteogenesis in mice.

    Carson, Matthew D / Warner, Amy J / Hathaway-Schrader, Jessica D / Geiser, Vincenza L / Kim, Joseph / Gerasco, Joy E / Hill, William D / Lemasters, John J / Alekseyenko, Alexander V / Wu, Yongren / Yao, Hai / Aguirre, J Ignacio / Westwater, Caroline / Novince, Chad M

    JCI insight

    2023  Volume 8, Issue 1

    Abstract: Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver ... ...

    Abstract Antibiotic-induced shifts in the indigenous gut microbiota influence normal skeletal maturation. Current theory implies that gut microbiota actions on bone occur through a direct gut/bone signaling axis. However, our prior work supports that a gut/liver signaling axis contributes to gut microbiota effects on bone. Our purpose was to investigate the effects of minocycline, a systemic antibiotic treatment for adolescent acne, on pubertal/postpubertal skeletal maturation. Sex-matched specific pathogen-free (SPF) and germ-free (GF) C57BL/6T mice were administered a clinically relevant minocycline dose from age 6-12 weeks. Minocycline caused dysbiotic shifts in the gut bacteriome and impaired skeletal maturation in SPF mice but did not alter the skeletal phenotype in GF mice. Minocycline administration in SPF mice disrupted the intestinal farnesoid X receptor/fibroblast growth factor 15 axis, a gut/liver endocrine axis supporting systemic bile acid homeostasis. Minocycline-treated SPF mice had increased serum conjugated bile acids that were farnesoid X receptor (FXR) antagonists, suppressed osteoblast function, decreased bone mass, and impaired bone microarchitecture and fracture resistance. Stimulating osteoblasts with the serum bile acid profile from minocycline-treated SPF mice recapitulated the suppressed osteogenic phenotype found in vivo, which was mediated through attenuated FXR signaling. This work introduces bile acids as a potentially novel mediator of gut/liver signaling actions contributing to gut microbiota effects on bone.
    MeSH term(s) Animals ; Mice ; Anti-Bacterial Agents/adverse effects ; Bile Acids and Salts/metabolism ; Liver/metabolism ; Mice, Inbred C57BL ; Minocycline/pharmacology ; Osteogenesis
    Chemical Substances Anti-Bacterial Agents ; Bile Acids and Salts ; Minocycline (FYY3R43WGO) ; fibroblast growth factor 15, mouse ; farnesoid X-activated receptor (0C5V0MRU6P)
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.160578
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Commensal gut bacterium critically regulates alveolar bone homeostasis.

    Hathaway-Schrader, Jessica D / Carson, Matthew D / Gerasco, Joy E / Warner, Amy J / Swanson, Brooks A / Aguirre, J Ignacio / Westwater, Caroline / Liu, Bei / Novince, Chad M

    Laboratory investigation; a journal of technical methods and pathology

    2021  Volume 102, Issue 4, Page(s) 363–375

    Abstract: The alveolar bone is a unique osseous tissue due to the presence of the teeth and the proximity of commensal oral microbes. Commensal microbe effects on alveolar bone homeostasis have been attributed to the oral microbiota, yet the impact of commensal ... ...

    Abstract The alveolar bone is a unique osseous tissue due to the presence of the teeth and the proximity of commensal oral microbes. Commensal microbe effects on alveolar bone homeostasis have been attributed to the oral microbiota, yet the impact of commensal gut microbes is unknown. Study purpose was to elucidate whether commensal gut microbes regulate osteoimmune mechanisms and skeletal homeostasis in alveolar bone. Male C57BL/6T germfree (GF) littermate mice were maintained as GF or monoassociated with segmented filamentous bacteria (SFB), a commensal gut bacterium. SFB has been shown to elicit broad immune response effects, including the induction of T
    MeSH term(s) Animals ; Bacteria ; Bone and Bones ; Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; Osteoclasts/metabolism ; Th17 Cells
    Language English
    Publishing date 2021-12-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80178-1
    ISSN 1530-0307 ; 0023-6837
    ISSN (online) 1530-0307
    ISSN 0023-6837
    DOI 10.1038/s41374-021-00697-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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