The microbiome is dispensable for normal respiratory function and chemoreflexes in mice

Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remov...

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Main Authors: Savannah Lusk, Nicoletta K. Memos, Andrea Rauschmayer, Russell S. Ray
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Physiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphys.2024.1481394/full
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author Savannah Lusk
Nicoletta K. Memos
Andrea Rauschmayer
Russell S. Ray
Russell S. Ray
author_facet Savannah Lusk
Nicoletta K. Memos
Andrea Rauschmayer
Russell S. Ray
Russell S. Ray
author_sort Savannah Lusk
collection DOAJ
description Increasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.
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spelling doaj-art-113bbf92ec9c43389db83efc671667fa2025-08-20T02:19:33ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2024-12-011510.3389/fphys.2024.14813941481394The microbiome is dispensable for normal respiratory function and chemoreflexes in miceSavannah Lusk0Nicoletta K. Memos1Andrea Rauschmayer2Russell S. Ray3Russell S. Ray4Department of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesDepartment of Neuroscience, Baylor College of Medicine, Houston, TX, United StatesBaylor College of Medicine, McNair Medical Institute, Houston, TX, United StatesIncreasing evidence indicates an association between microbiome composition and respiratory homeostasis and disease, particularly disordered breathing, such as obstructive sleep apnea. Previous work showing respiratory disruption is limited by the methodology employed to disrupt, eliminate, or remove the microbiome by antibiotic depletion. Our work utilized germ-free mice born without a microbiome and described respiratory alterations. We used whole-body flow through barometric plethysmography to assay conscious and unrestrained C57BL/6J germ-free (GF, n = 24) and specific-pathogen-free (SPF, n = 28) adult mice (with an intact microbiome) in normoxic (21% O2,79% N2) conditions and during challenges in hypercapnic (5% CO2, 21% O2, 74% N2) and hypoxic (10% O2, 90% N2) environments. Following initial plethysmography analysis, we performed fecal transplants to test the ability of gut microbiome establishment to rescue any observed phenotypes. Data were comprehensively analyzed using our newly published respiratory analysis software, Breathe Easy, to identify alterations in respiratory parameters, including ventilatory frequency, tidal volume, ventilation, apnea frequency, and sigh frequency. We also considered possible metabolic changes by analyzing oxygen consumption, carbon dioxide production, and ventilatory equivalents of oxygen. We also assayed GF and SPF neonates in an autoresuscitation assay to understand the effects of the microbiome on cardiorespiratory stressors in early development. We found several differences in baseline and recovery cardiorespiratory parameters in the neonates and differences in body weight at both ages studied. However, there was no difference in the overall survival of the neonates, and in contrast to prior studies utilizing gut microbial depletion, we found no consequential respiratory alterations in GF versus SPF adult mice at baseline or following fecal transplant in any groups. Interestingly, we did see alterations in oxygen consumption in the GF adult mice, which suggests an altered metabolic demand. Results from this study suggest that microbiome alteration in mice may not play as large a role in respiratory outcomes when a less severe methodology to eliminate the microbiome is utilized.https://www.frontiersin.org/articles/10.3389/fphys.2024.1481394/fullmicrobiomebreathingdysbiosisgerm-freemice
spellingShingle Savannah Lusk
Nicoletta K. Memos
Andrea Rauschmayer
Russell S. Ray
Russell S. Ray
The microbiome is dispensable for normal respiratory function and chemoreflexes in mice
Frontiers in Physiology
microbiome
breathing
dysbiosis
germ-free
mice
title The microbiome is dispensable for normal respiratory function and chemoreflexes in mice
title_full The microbiome is dispensable for normal respiratory function and chemoreflexes in mice
title_fullStr The microbiome is dispensable for normal respiratory function and chemoreflexes in mice
title_full_unstemmed The microbiome is dispensable for normal respiratory function and chemoreflexes in mice
title_short The microbiome is dispensable for normal respiratory function and chemoreflexes in mice
title_sort microbiome is dispensable for normal respiratory function and chemoreflexes in mice
topic microbiome
breathing
dysbiosis
germ-free
mice
url https://www.frontiersin.org/articles/10.3389/fphys.2024.1481394/full
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