TY - JOUR
T1 - Postnatal colonization with human "infant-type" Bifidobacterium species alters behavior of adult gnotobiotic mice
AU - Luk, Berkley
AU - Veeraragavan, Surabi
AU - Engevik, Melinda
AU - Balderas, Miriam
AU - Major, Angela
AU - Runge, Jessica
AU - Luna, Ruth Ann
AU - Versalovic, James
N1 - Funding Information:
This work was supported by funding from Texas Children’s Hospital (Houston, Texas, USA), the National Institutes of Health to James Versalovic including the Texas Medical Center Digestive Disease Center (P30 DK56338), National Cancer Institute (U01 CA170930), and unrestricted research support from BioGaia AB (Stockholm, Sweden) to James Versalovic. The project was supported in part by Baylor College of Medicine IDDRC Grant Number U54HD083092 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was supported by funding from Texas Children’s Hospital (Houston, Texas, USA), the National Institutes of Health to JV, including the Texas Medical Center Digestive Diseases Center (P30 DK56338), National Cancer Institute (U01 CA170930), and unrestricted research support from BioGaia AB (Stockholm, Sweden) (JV). The project was supported in part by Baylor College of Medicine IDDRC Grant Number U54HD083092 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors acknowledge the support of Texas Children’s Hospital and the resources within the Texas Children’s Microbiome Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank Dr. Roy Sillitoe for critical review of the manuscript.
Publisher Copyright:
© 2018 Luk et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/5
Y1 - 2018/5
N2 - Accumulating studies have defined a role for the intestinal microbiota in modulation of host behavior. Research using gnotobiotic mice emphasizes that early microbial colonization with a complex microbiota (conventionalization) can rescue some of the behavioral abnormalities observed in mice that grow to adulthood completely devoid of bacteria (germ-free mice). However, the human infant and adult microbiomes vary greatly, and effects of the neonatal microbiome on neurodevelopment are currently not well understood. Microbe-mediated modulation of neural circuit patterning in the brain during neurodevelopment may have significant long-term implications that we are only beginning to appreciate. Modulation of the host central nervous system by the early-life microbiota is predicted to have pervasive and lasting effects on brain function and behavior. We sought to replicate this early microbe-host interaction by colonizing gnotobiotic mice at the neonatal stage with a simplified model of the human infant gut microbiota. This model consortium consisted of four “infant-type” Bifidobacterium species known to be commensal members of the human infant microbiota present in high abundance during postnatal development. Germ-free mice and mice neonatally-colonized with a complex, conventional murine microbiota were used for comparison. Motor and non-motor behaviors of the mice were tested at 6–7 weeks of age, and colonization patterns were characterized by 16S ribosomal RNA gene sequencing. Adult germ-free mice were observed to have abnormal memory, sociability, anxiety-like behaviors, and motor performance. Con-ventionalization at the neonatal stage rescued these behavioral abnormalities, and mice colonized with Bifidobacterium spp. also exhibited important behavioral differences relative to the germ-free controls. The ability of Bifidobacterium spp. to improve the recognition memory of both male and female germ-free mice was a prominent finding. Together, these data demonstrate that the early-life gut microbiome, and human “infant-type” Bifidobacterium species, affect adult behavior in a strongly sex-dependent manner, and can selectively recapitulate the results observed when mice are colonized with a complex microbiota.
AB - Accumulating studies have defined a role for the intestinal microbiota in modulation of host behavior. Research using gnotobiotic mice emphasizes that early microbial colonization with a complex microbiota (conventionalization) can rescue some of the behavioral abnormalities observed in mice that grow to adulthood completely devoid of bacteria (germ-free mice). However, the human infant and adult microbiomes vary greatly, and effects of the neonatal microbiome on neurodevelopment are currently not well understood. Microbe-mediated modulation of neural circuit patterning in the brain during neurodevelopment may have significant long-term implications that we are only beginning to appreciate. Modulation of the host central nervous system by the early-life microbiota is predicted to have pervasive and lasting effects on brain function and behavior. We sought to replicate this early microbe-host interaction by colonizing gnotobiotic mice at the neonatal stage with a simplified model of the human infant gut microbiota. This model consortium consisted of four “infant-type” Bifidobacterium species known to be commensal members of the human infant microbiota present in high abundance during postnatal development. Germ-free mice and mice neonatally-colonized with a complex, conventional murine microbiota were used for comparison. Motor and non-motor behaviors of the mice were tested at 6–7 weeks of age, and colonization patterns were characterized by 16S ribosomal RNA gene sequencing. Adult germ-free mice were observed to have abnormal memory, sociability, anxiety-like behaviors, and motor performance. Con-ventionalization at the neonatal stage rescued these behavioral abnormalities, and mice colonized with Bifidobacterium spp. also exhibited important behavioral differences relative to the germ-free controls. The ability of Bifidobacterium spp. to improve the recognition memory of both male and female germ-free mice was a prominent finding. Together, these data demonstrate that the early-life gut microbiome, and human “infant-type” Bifidobacterium species, affect adult behavior in a strongly sex-dependent manner, and can selectively recapitulate the results observed when mice are colonized with a complex microbiota.
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U2 - 10.1371/journal.pone.0196510
DO - 10.1371/journal.pone.0196510
M3 - Article
C2 - 29763437
AN - SCOPUS:85047113803
VL - 13
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 5
M1 - e0196510
ER -