skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


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
Award ID(s):
1655362
PAR ID:
10287538
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
Journal of Experimental Biology
Volume:
224
Issue:
4
ISSN:
0022-0949
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Dietary factors modulate interactions between the microbiome, metabolome, and immune system. Sulforaphane (SFN) exerts effects on aging, cancer prevention and reducing insulin resistance. This study investigated effects of SFN on the gut microbiome and metabolome in old mouse model compared with young mice. Young (6–8 weeks) and old (21–22 months) male C57BL/6J mice were provided regular rodent chow ± SFN for 2 months. We collected fecal samples before and after SFN administration and profiled the microbiome and metabolome. Multi-omics datasets were analyzed individually and integrated to investigate the relationship between SFN diet, the gut microbiome, and metabolome. The SFN diet restored the gut microbiome in old mice to mimic that in young mice, enriching bacteria known to be associated with an improved intestinal barrier function and the production of anti-inflammatory compounds. The tricarboxylic acid cycle decreased and amino acid metabolism-related pathways increased. Integration of multi-omic datasets revealed SFN diet-induced metabolite biomarkers in old mice associated principally with the genera, Oscillospira, Ruminococcus, and Allobaculum. Collectively, our results support a hypothesis that SFN diet exerts anti-aging effects in part by influencing the gut microbiome and metabolome. Modulating the gut microbiome by SFN may have the potential to promote healthier aging. 
    more » « less
  2. Chu, Hiutung (Ed.)
    ABSTRACT Crohn’s disease (CD) is a presentation of inflammatory bowel disease (IBD) that manifests in childhood and adolescence and involves chronic and severe enterocolitis, immune and gut microbial dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories that could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites. Many studies on diet and IBD use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated CD model. Interleukin-10-knockout (IL-10-KO) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed a control diet or one containing 10% (wt/wt) raw broccoli sprouts, which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to, and for 2 weeks after inoculation withHelicobacter hepaticus,which triggers Crohn’s-like symptoms in these immune-impaired mice. The broccoli sprout diet increased sulforaphane in plasma; decreased weight stagnation, fecal blood, and diarrhea associated; and increased microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacteria in younger mice and reduced the prevalence and abundance of pathobiont bacteria which trigger inflammation in the IL-10-KO mouse, for example,Escherichia coliandHelicobacter. Overall, the IL-10-KO mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research. IMPORTANCETo our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn’s disease disrupts the lives of patients and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms. 
    more » « less
  3. BackgroundHigh-Runner (HR) mice, selectively bred for increased voluntary wheel running behavior, exhibit heightened motivation to run. Exercise has been shown to influence hippocampal long-term potentiation (LTP) and memory, and is neuroprotective in several neurodegenerative diseases. ObjectiveThis study aimed to determine the impact of intense running in HR mice with wheel access on hippocampal LTP, compared to HR mice without wheels and non-selected control (C) mice with/without wheels. Additionally, we investigated the involvement of D1/D5 receptors and the dopamine transporter (DAT) in LTP modulation and examined levels of these proteins in HR and C mice. MethodsAdult female HR and C mice were individually housed with/without running wheels for at least two weeks. Hippocampal LTP of extracellular field excitatory postsynaptic potentials (fEPSPs) was measured in area CA1, and SKF-38393 (D1/D5 receptor agonist) and GBR 12909 (DAT inhibitor) were used to probe the role of D1/D5 receptors and DAT in LTP differences. Western blot analyses assessed D1/D5 receptor and DAT expression in the hippocampus, prefrontal cortex, and cerebellum. ResultsHR mice with wheel access showed significantly increased hippocampal LTP compared to those without wheels and to C mice with/without wheels. Treatment with SKF-38393 or GBR 12909 prevented the heightened LTP in HR mice with wheels, aligning it with levels in C mice. Hippocampal D1/D5 receptor levels were lower, and DAT levels were higher in HR mice compared to C mice. No significant changes were observed in other brain regions. ConclusionsThe increased hippocampal LTP seen in HR mice with wheel access may be related to alterations in dopaminergic synaptic transmission that underlie the neurophysiological basis of hyperactivity, motor disorders, and/or motivation. 
    more » « less
  4. Abstract ObjectivesLittle 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 MethodsThe 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. ResultsResults 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. DiscussionThese 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. 
    more » « less
  5. Abstract The nutrient artery provides ~50%–70% of the total blood volume to long bones in mammals. Studying the functional characteristics of this artery in vivo can be difficult and expensive, so most researchers have measured the nutrient foramen, an opening on the outer surface of the bone that served as the entry point for the nutrient artery during development and bone ossification. Others have measured the nutrient canal (i.e., the passage which the nutrient artery once occupied), given that the external dimensions of the foramen do not necessarily remain uniform from the periosteal surface to the medullary cavity. The nutrient canal, as an indicator of blood flow to long bones, has been proposed to provide a link to studying organismal activity (e.g., locomotor behavior) from skeletal morphology. However, although external loading from movement and activity causes skeletal remodeling, it is unclear whether it affects the size or configuration of nutrient canals. To investigate whether nutrient canals can exhibit phenotypic plasticity in response to physical activity, we studied a mouse model in which four replicate high runner (HR) lines have been selectively bred for high voluntary wheel‐running behavior. The selection criterion is the average number of wheel revolutions on days 5 and 6 of a 6‐day period of wheel access as young adults (~6–8 weeks old). An additional four lines are bred without selection to serve as controls (C). For this study, 100 female mice (half HR, half C) from generation 57 were split into an active group housed with wheels and a sedentary group housed without wheels for 12 weeks starting at ~24 days of age. Femurs were collected, soft tissues were removed, and femora were micro‐computed tomography scanned at a resolution of 12 μm. We then imported these scans into AMIRA and created 3D models of femoral nutrient canals. We tested for evolved differences in various nutrient canal traits between HR and C mice, plastic changes resulting from chronic exercise, and the selection history‐by‐exercise interaction. We found few differences between the nutrient canals of HR versus C mice, or between the active and sedentary groups. We did find an interaction between selection history and voluntary exercise for the total number of nutrient canals per femur, in which wheel access increased the number of canals in C mice but decreased it in HR mice. Our results do not match those from an earlier study, conducted at generation 11, which was prior to the HR lines reaching selection limits for wheel running. The previous study found that mice from the HR lines had significantly larger total canal cross‐sectional areas compared to those from C lines. However, this discrepancy is consistent with studies of other skeletal traits, which have found differences between HR and C mice to be somewhat inconsistent across generations, including the loss of some apparent adaptations with continued selective breeding after reaching a selection limit for wheel‐running behavior. 
    more » « less