Title: Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice
ABSTRACT Alterations to the gut microbiome caused by changes in diet, consumption of antibiotics, etc., can affect host function. Moreover, perturbation of the microbiome during critical developmental periods potentially has long-lasting impacts on hosts. Using four selectively bred high runner and four non-selected control lines of mice, we examined the effects of early-life diet and exercise manipulations on the adult microbiome by sequencing the hypervariable internal transcribed spacer region of the bacterial gut community. Mice from high runner lines run ∼3-fold more on wheels than do controls, and have several other phenotypic differences (e.g. higher food consumption and body temperature) that could alter the microbiome, either acutely or in terms of coevolution. Males from generation 76 were given wheels and/or a Western diet from weaning until sexual maturity at 6 weeks of age, then housed individually without wheels on standard diet until 14 weeks of age, when fecal samples were taken. Juvenile Western diet reduced bacterial richness and diversity after the 8-week washout period (equivalent to ∼6 human years). We also found interactive effects of genetic line type, juvenile diet and/or juvenile exercise on microbiome composition and diversity. Microbial community structure clustered significantly in relation to both line type and diet. Western diet also reduced the relative abundance of Muribaculum intestinale. These results constitute one of the first reports of juvenile diet having long-lasting effects on the adult microbiome after a substantial washout period. Moreover, we found interactive effects of diet with early-life exercise exposure, and a dependence of these effects on genetic background. more »« less
Lewton, Kristi L.; Ritzman, Terrence; Copes, Lynn E.; Garland, Jr, Theodore; Capellini, Terence D.(
, American Journal of Physical Anthropology)
AbstractObjectives
Little is known about how ilium cortical bone responds to loading. Using a mouse model, this study presents data testing the hypothesis that iliac cross‐sectional properties are altered in response to increased activity.
Materials and Methods
The sample derives from lines of High Runner (HR) mice bred for increased wheel‐running activity. Four treatment groups of female mice were tested: non‐selected control lines housed without (N = 19) and with wheels (N = 20), and HR mice housed without (N = 17) and with wheels (N = 18) for 13 weeks beginning at weaning. Each pelvis was μCT‐scanned, cross‐sectional properties (cortical area—Ct.Ar, total area—Tt.Ar, polar moment of area, and polar section modulus) were determined from the ilium midshaft, and robusticity indices (ratio of the square root ofCt.ArorTt.Arto caudal ilium length) were calculated. Mixed models were implemented with linetype, wheel access, and presence of the mini‐muscle phenotype as fixed effects, replicate line nested within linetype as a random effect, and body mass as a covariate.
Results
Results demonstrate that the mouse ilium morphologically resembles a long bone in cross section. Body mass and the mini‐muscle phenotype were significant predictors of iliac cross‐sectional properties. Wheel access only had a statistically significant effect onCt.Arand its robusticity index, with greater values in mice with wheel access.
Discussion
These results suggest that voluntary exercise increases cortical area, but does not otherwise strengthen the ilium in these mice, corroborating previous studies on the effect of increased wheel‐running activity on femoral and humeral cross‐sectional properties in these mice.
Rojas, Connie A.; Holekamp, Kay E.; Viladomat Jasso, Mariette; Souza, Valeria; Eisen, Jonathan A.; Theis, Kevin R.(
, mSystems)
Hird, Sarah M.
(Ed.)
The gut microbiome provides vital functions for mammalian hosts, yet research on its variability and function across adult life spans and multiple generations is limited in large mammalian carnivores. Here, we used 16S rRNA gene and metagenomic high-throughput sequencing to profile the bacterial taxonomic composition, genomic diversity, and metabolic function of fecal samples collected from 12 wild spotted hyenas ( Crocuta crocuta ) residing in the Masai Mara National Reserve, Kenya, over a 23-year period spanning three generations. The metagenomic data came from four of these hyenas and spanned two 2-year periods. With these data, we determined the extent to which host factors predicted variation in the gut microbiome and identified the core microbes present in the guts of hyenas. We also investigated novel genomic diversity in the mammalian gut by reporting the first metagenome-assembled genomes (MAGs) for hyenas. We found that gut microbiome taxonomic composition varied temporally, but despite this, a core set of 14 bacterial genera were identified. The strongest predictors of the microbiome were host identity and age, suggesting that hyenas possess individualized microbiomes and that these may change with age during adulthood. The gut microbiome functional profiles of the four adult hyenas were also individual specific and were associated with prey abundance, indicating that the functions of the gut microbiome vary with host diet. We recovered 149 high-quality MAGs from the hyenas’ guts; some MAGs were classified as taxa previously reported for other carnivores, but many were novel and lacked species-level matches to genomes in existing reference databases. IMPORTANCE There is a gap in knowledge regarding the genomic diversity and variation of the gut microbiome across a host’s life span and across multiple generations of hosts in wild mammals. Using two types of sequencing approaches, we found that although gut microbiomes were individualized and temporally variable among hyenas, they correlated similarly to large-scale changes in the ecological conditions experienced by their hosts. We also recovered 149 high-quality MAGs from the hyena gut, greatly expanding the microbial genome repertoire known for hyenas, carnivores, and wild mammals in general. Some MAGs came from genera abundant in the gastrointestinal tracts of canid species and other carnivores, but over 80% of MAGs were novel and from species not previously represented in genome databases. Collectively, our novel body of work illustrates the importance of surveying the gut microbiome of nonmodel wild hosts, using multiple sequencing methods and computational approaches and at distinct scales of analysis.
Copes, L. E.; Schutz, H.; Dlugsoz, E. M.; Judex, S.; Garland, Jr, T.(
, American Journal of Physical Anthropology)
AbstractObjectives
To use a mouse model to investigate the relationships among the components of the systemic robusticity hypothesis (SRH): voluntary exercise on wheels, spontaneous physical activity (SPA) in cages, growth hormones, and skeletal robusticity, especially cranial vault thickness (CVT).
Materials and Methods
Fifty female mice from lines artificially selected for high running (HR) and 50 from nonselected control (C) lines were housed in cages with (Active) or without wheels (Sedentary). Wheel running and SPA were monitored daily. The experiment began at 24–27 days of age and lasted 12 weeks. Food consumption was measured weekly. Mice were skeletonized and their interparietal, parietal, humerus, and femur were µCT scanned. Mean total thickness of the parietal and interparietal bones was determined, along with thickness of the cortical and diploe layers individually. Geometric cross‐sectional indicators of strength were calculated for the long bones. Blood samples were assayed for IGF‐1 and IGFBP‐3.
Results
Physical activity differed significantly among groups, based both on linetype (C vs. HR) and activity (A vs. S). However, contrary to our predictions, the ratio of IGF‐1 to IGFBP‐3 was higher in C mice than in HR mice. Neither CVT nor postcranial robusticity was affected by linetype or activity, nor were most measures of CVT and postcranial robusticity significantly associated with one another.
Discussion
Our results fail to provide support for the systemic robusticity hypothesis, suggesting it is important to rethink the long‐standing theory that increased CVT inHomo erectusreflects increased physical activity compared other hominin species.
Bone modeling and remodeling are aerobic processes that entail relatively high oxygen demands. Long bones receive oxygenated blood from nutrient arteries, epiphyseal‐metaphyseal arteries, and periosteal arteries, with the nutrient artery supplying the bulk of total blood volume in mammals (~ 50–70%). Estimates of blood flow into these bones can be made from the dimensions of the nutrient canal, through which nutrient arteries pass. Unfortunately, measuring these canal dimensions non‐invasively (i.e. without physical sectioning) is difficult, and thus researchers have relied on more readily visible skeletal proxies. Specifically, the size of the nutrient artery has been estimated from dimensions (e.g. minimum diameters) of the periosteal (external) opening of the nutrient canal. This approach has also been utilized by some comparative morphologists and paleontologists, as the opening of a nutrient canal is present long after the vascular soft tissue has degenerated. The literature on nutrient arteries and canals is sparse, with most studies consisting of anatomical descriptions from surgical proceedings, and only a few investigating the links between nutrient canal morphology and physiology or behavior. The primary objective of this study was to evaluate femur nutrient canal morphology in mice with known physiological and behavioral differences; specifically, mice from an artificial selection experiment for high voluntary wheel‐running behavior. Mice from four replicate high runner (HR) lines are known to differ from four non‐selected control (C) lines in both locomotor and metabolic activity, withHRmice having increased voluntary wheel‐running behavior and maximal aerobic capacity (VO2max) during forced treadmill exercise. Femora from adult mice (average age 7.5 months) of the 11th generation of this selection experiment were μCT‐scanned and three‐dimensional virtual reconstructions of nutrient canals were measured for minimum cross‐sectional area as a skeletal proxy of blood flow. Gross observations revealed that nutrient canals varied far more in number and shape than prior descriptions would indicate, regardless of sex or genetic background (i.e.HRvs. C lines). Canals adopted non‐linear shapes and paths as they traversed from the periosteal to endosteal borders through the cortex, occasionally even branching within the cortical bone. Additionally, mice from bothHRand C lines averaged more than four nutrient canals per femur, in contrast to the one to two nutrient canals described for femora from rats, pigs, and humans in prior literature. Mice fromHRlines had significantly larger total nutrient canal area than C lines, which was the result not of an increase in the number of nutrient canals, but rather an increase in their average cross‐section size. This study demonstrates that mice with an evolutionary history of increased locomotor activity and maximal aerobic metabolic rate have a concomitant increase in the size of their femoral nutrient canals. Although the primary determinant of nutrient canal size is currently not well understood, the present results bolster use of nutrient canal size as a skeletal indicator of aerobically supported levels of physical activity in comparative studies.
McNamara, Monica P., Singleton, Jennifer M., Cadney, Marcell D., Ruegger, Paul M., Borneman, James, and Garland, Theodore. Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice. Retrieved from https://par.nsf.gov/biblio/10287538. Journal of Experimental Biology 224.4 Web. doi:10.1242/jeb.239699.
McNamara, Monica P., Singleton, Jennifer M., Cadney, Marcell D., Ruegger, Paul M., Borneman, James, & Garland, Theodore. Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice. Journal of Experimental Biology, 224 (4). Retrieved from https://par.nsf.gov/biblio/10287538. https://doi.org/10.1242/jeb.239699
McNamara, Monica P., Singleton, Jennifer M., Cadney, Marcell D., Ruegger, Paul M., Borneman, James, and Garland, Theodore.
"Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice". Journal of Experimental Biology 224 (4). Country unknown/Code not available. https://doi.org/10.1242/jeb.239699.https://par.nsf.gov/biblio/10287538.
@article{osti_10287538,
place = {Country unknown/Code not available},
title = {Early-life effects of juvenile Western diet and exercise on adult gut microbiome composition in mice},
url = {https://par.nsf.gov/biblio/10287538},
DOI = {10.1242/jeb.239699},
abstractNote = {ABSTRACT Alterations to the gut microbiome caused by changes in diet, consumption of antibiotics, etc., can affect host function. Moreover, perturbation of the microbiome during critical developmental periods potentially has long-lasting impacts on hosts. Using four selectively bred high runner and four non-selected control lines of mice, we examined the effects of early-life diet and exercise manipulations on the adult microbiome by sequencing the hypervariable internal transcribed spacer region of the bacterial gut community. Mice from high runner lines run ∼3-fold more on wheels than do controls, and have several other phenotypic differences (e.g. higher food consumption and body temperature) that could alter the microbiome, either acutely or in terms of coevolution. Males from generation 76 were given wheels and/or a Western diet from weaning until sexual maturity at 6 weeks of age, then housed individually without wheels on standard diet until 14 weeks of age, when fecal samples were taken. Juvenile Western diet reduced bacterial richness and diversity after the 8-week washout period (equivalent to ∼6 human years). We also found interactive effects of genetic line type, juvenile diet and/or juvenile exercise on microbiome composition and diversity. Microbial community structure clustered significantly in relation to both line type and diet. Western diet also reduced the relative abundance of Muribaculum intestinale. These results constitute one of the first reports of juvenile diet having long-lasting effects on the adult microbiome after a substantial washout period. Moreover, we found interactive effects of diet with early-life exercise exposure, and a dependence of these effects on genetic background.},
journal = {Journal of Experimental Biology},
volume = {224},
number = {4},
author = {McNamara, Monica P. and Singleton, Jennifer M. and Cadney, Marcell D. and Ruegger, Paul M. and Borneman, James and Garland, Theodore},
editor = {null}
}
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