Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight

Joseph K Bedree; Kristopher Kerns; Tsute Chen; Bruno P Lima; Guo Liu; Pin Ha; Jiayu Shi; Hsin Chuan Pan; Jong Kil Kim; Luan Tran; Samuel S Minot; Erik L Hendrickson; Eleanor I Lamont; Fabian Schulte; Markus Hardt; Danielle Stephens; Michele Patel; Alexis Kokaras; Louis Stodieck; Yasaman Shirazi-Fard; Benjamin Wu; Jin Hee Kwak; Kang Ting; Chia Soo; Jeffrey S McLean; Xuesong He; Wenyuan Shi

doi:10.1016/j.celrep.2023.112299

Specific host metabolite and gut microbiome alterations are associated with bone loss during spaceflight

Cell Rep. 2023 May 30;42(5):112299. doi: 10.1016/j.celrep.2023.112299. Epub 2023 Apr 19.

Authors

Joseph K Bedree¹, Kristopher Kerns², Tsute Chen³, Bruno P Lima⁴, Guo Liu⁵, Pin Ha⁶, Jiayu Shi⁷, Hsin Chuan Pan⁵, Jong Kil Kim⁵, Luan Tran⁵, Samuel S Minot⁸, Erik L Hendrickson², Eleanor I Lamont², Fabian Schulte⁹, Markus Hardt⁹, Danielle Stephens¹⁰, Michele Patel¹⁰, Alexis Kokaras¹¹, Louis Stodieck¹², Yasaman Shirazi-Fard¹³, Benjamin Wu¹⁴, Jin Hee Kwak¹⁵, Kang Ting¹⁵, Chia Soo¹⁶, Jeffrey S McLean², Xuesong He³, Wenyuan Shi¹⁷

Affiliations

¹ Section of Oral Biology, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142, USA. Electronic address: jkbedree@ucla.edu.
² Department of Periodontics, School of Dentistry, University of Washington, Seattle, WA 98195, USA.
³ Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142, USA; Department of Oral Medicine, Infection and Immunity, Harvard School of Dental Medicine, Boston, MA 02115, USA.
⁴ Department of Diagnostic and Biological Sciences, University of Minnesota, Minneapolis, MN 55455, USA.
⁵ Section of Oral Biology, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁶ Section of Orthodontics, Division of Growth & Development, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Plastic and Reconstructive Surgery, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁷ Section of Oral Biology, Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI 48109, USA.
⁸ Microbiome Research Initiative, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
⁹ Forsyth Center for Salivary Diagnostics, Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142, USA; Harvard School of Dental Medicine, Department of Developmental Biology, Boston, MA 02115, USA.
¹⁰ Multiplex Core, Department of Applied Oral Sciences, The Forsyth Institute, Cambridge, MA 02142, USA.
¹¹ Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142, USA.
¹² BioServe Space Technologies, Department of Aerospace Engineering Sciences, University of Colorado, Boulder, CO 80303, USA.
¹³ Bone and Signaling Laboratory, Space Biosciences Division, NASA Ames Research Center, Mail Stop 288-2, Moffett Field, CA 94035, USA.
¹⁴ Department of Bioengineering, School of Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Advanced Prosthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁵ Section of Orthodontics, Division of Growth & Development, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁶ Division of Plastic and Reconstructive Surgery, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Orthopedic Surgery, School of Medicine, School of Dentistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁷ Department of Microbiology, The Forsyth Institute, Cambridge, MA 02142, USA. Electronic address: wshi@forsyth.org.

Abstract

Understanding the axis of the human microbiome and physiological homeostasis is an essential task in managing deep-space-travel-associated health risks. The NASA-led Rodent Research 5 mission enabled an ancillary investigation of the gut microbiome, varying exposure to microgravity (flight) relative to ground controls in the context of previously shown bone mineral density (BMD) loss that was observed in these flight groups. We demonstrate elevated abundance of Lactobacillus murinus and Dorea sp. during microgravity exposure relative to ground control through whole-genome sequencing and 16S rRNA analyses. Specific functionally assigned gene clusters of L. murinus and Dorea sp. capable of producing metabolites, lactic acid, leucine/isoleucine, and glutathione are enriched. These metabolites are elevated in the microgravity-exposed host serum as shown by liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. Along with BMD loss, ELISA reveals increases in osteocalcin and reductions in tartrate-resistant acid phosphatase 5b signifying additional loss of bone homeostasis in flight.

Keywords: CP: Metabolism; International Space Station National Laboratory; Rodent Research; bone homeostasis; gut microbiome; gut-bone axis; microgravity; oral microbiome.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Chromatography, Liquid
Gastrointestinal Microbiome*
Humans
RNA, Ribosomal, 16S / genetics
Space Flight*
Tandem Mass Spectrometry
Travel

Substances

RNA, Ribosomal, 16S

Abstract

Publication types

MeSH terms

Substances

Grants and funding