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The gastrointestinal tract contains trillions of microbes (collectively known as the gut microbiota) that play essential roles in host physiology and health. Studies from our group and others have demonstrated that exercise independently alters the composition and functional capacity of the gut microbiota. Here, we review what is known about the gut microbiota, how it is studied, and how it is influenced by exercise training and discuss the potential mechanisms and implications for human health and disease.
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Copyright © 2019 by the American College of Sports Medicine
ESSR Published Ahead-of-Print
Heading: Perspectives for Progress
Accepted: 01/18/2019
Editor: Marni D. Boppart, ScD, FACSM
Exercise and the gut microbiome: a review of the evidence, potential mechanisms, and
implications for human health
Lucy J. Mailing1, Jacob M. Allen2, Thomas W. Buford3, Christopher J. Fields4, Jeffrey A.
1 Division of Nutritional Sciences, University of Illinois Urbana-Champaign, IL
2 Center for Microbial Pathogenesis, Nationwide Children‘s Hospital, Columbus, OH
3 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL
4 High Performance Computing in Biology, Carver Biotechnology Center, University of Illinois
Urbana-Champaign, IL
5 Department of Kinesiology and Community Health, University of Illinois Urbana-Champaign,
Exercise and the gut microbiome: a review of the evidence, potential
mechanisms, and implications for human health
Lucy J. Mailing1, Jacob M. Allen2, Thomas W. Buford3, Christopher J. Fields4, Jeffrey A.
1 Division of Nutritional Sciences, University of Illinois Urbana-Champaign, IL, United States
2 Center for Microbial Pathogenesis, Nationwide Children‘s Hospital, Columbus, OH, United
3 Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United
4 High Performance Computing in Biology, Carver Biotechnology Center, University of Illinois
Urbana-Champaign, IL, United States
5 Department of Kinesiology and Community Health, University of Illinois Urbana-Champaign,
IL, United States
Corresponding Author:
Jeffrey A. Woods, PhD
1206 South 4th Street
1008A Khan Annex, Huff Hall
University of Illinois at Urbana-Champaign
Champaign IL 61820
Exercise and Sport Sciences Reviews, Publish Ahead of Print
DOI: 10.1249/JES.0000000000000183
Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Funding: The authors have no funding to disclose for the preparation of this manuscript. TB‘s
effort toward this manuscript partially supported by grants from the National Institutes of Health
(P2CHD086851 and P30AG050886).
Conflicts of interest: The authors have no conflicts of interest to report.
Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
The gastrointestinal tract contains trillions of microbes (collectively known as the gut
microbiota) that play essential roles in host physiology and health. Studies from our group and
others have demonstrated that exercise independently alters the composition and functional
capacity of the gut microbiota. Here, we review what is known about the gut microbiota, how it
is studied, how it is influenced by exercise training, and discuss the potential mechanisms and
implications for human health and disease.
KEYWORDS: Endurance exercise; gut microbiota; short-chain fatty acids; butyrate; gut health;
inflammatory bowel disease
The trillions of microbes in the gut play essential roles in human health
Exercise training alters the composition and functional capacity of the gut microbiota,
independent of diet
Exercise-induced alterations of the gut microbiota may depend on obesity status, exercise
modality, and exercise intensity.
Exercise-induced alterations of the gut microbiota are likely to have numerous benefits
for human health
Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
Scientists have only recently begun to appreciate the human gut as a complex ecosystem of
bacteria, archaea, eukaryotes, and viruses that have co-evolved with humans over thousands of
years. Known collectively as the gut microbiota, these microbes can weigh up to two kilograms
and are imperative to host digestion, metabolic function, and resistance to infection (1). The
human gut microbiota has an enormous metabolic capacity, with over 1000 different unique
bacterial species and over 3 million unique genes (2). Collectively, the sum of the microbial
genes in the gut is called the gut microbiome.
Given the numerous roles of the gut microbiota in host physiology and pathophysiology, it‘s not
surprising that there is great interest in identifying ways to manipulate microbial communities in
health and disease (35). While diet is well known to modulate the composition of the gut
microbiota, recent studies suggest that exercise can alter gut microbial communities as well. This
will be the focus of the present review. Key questions include: Does exercise independently alter
the gut microbiota? If yes, by what mechanism? With what implications for the gut and other
organ systems? Can exercise beneficially modulate the gut microbiota in states of disease?
Before we attempt to answer these questions, we will first review advances in technology that
have improved the understanding of the microbiota‘s contribution to health and disease and
enabled investigations into exercise‘s impact on gut microbial communities.
Until the 1990s, scientific study of gut microbes primarily relied on culture, staining, and
microscopy (6). Growth media and conditions typically favored fast-growing, aerobic microbes,
meaning that many anaerobic microbes could not be effectively cultured or studied (7). This
changed with the advent of DNA sequencing. 16S bacterial ribosomal RNA (rRNA) gene
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sequencing (hereafter 16S) quickly became the most popular (8). The conserved regions of this
gene are used to design broad-spectrum PCR primers that allow for the amplification of the more
rapidly-evolving hypervariable regions across a broad spectrum of microbes (Figure 1). The
resulting amplified hypervariable region sequences can then be classified taxonomically by
comparing them to a curated database of fully sequenced bacterial 16S genes (9).
16S is still the most widely used method to cost-effectively characterize bacterial communities in
a research setting (10), but it does have several limitations. First, taxonomic classifications are
limited primarily to bacteria. Second, sequence classification is normally limited to the genus
level, as multiple species may have the same sequence within the studied hypervariable region
(11). 16S is also susceptible to primer bias (12,13). Finally, 16S analysis does not provide direct
information about the function of gut microbes or the potential interactions with host physiology,
though tools such as PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of
Unobserved States) can infer potential functional pathways from 16S results utilizing
information from the Human Microbiome Project (14).
Recently, interest has increased for moving beyond 16S (‗who‘s there?‘) to better understand the
role of the gut microbiota in states of health and disease (‗what are they doing?‘). One way to do
this involves using specific degenerate primers to perform quantitative PCR (qPCR) for a
specific conserved microbial gene. For example, our lab has targeted the butyryl-CoA:acetate-
CoA transferase (BCoAT) gene, which encodes the primary enzyme involved in gut bacterial
production of the short-chain fatty acid (SCFA) butyrate (15). This targeted genomics approach
is relatively quick and inexpensive but limited in overall scope.
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In contrast, metagenomics (i.e. shotgun sequencing) involves assessing the entire gene content of
a given microbial community (16) to assess microbial functions and allow for identification of
bacteria, archaea, viruses, and fungi with greater specificity (2,17). Current limitations for
metagenomics include high cost, sequencing biases, complexity in both data processing and
analysis, and incomplete databases for taxonomy and genomic assignment (16). Nevertheless,
newer sequencing technologies as well as upgraded downstream pipelines (18,19) and reference
databases (20,21) have greatly improved taxonomic and functional genomic profiling of the gut
microbiota. Other meta-omics, such as meta-transcriptomics, -proteomics, and -metabolomics
can help elucidate which genes are actually expressed and become functional proteins capable of
carrying out diverse metabolic functions (22). These high-throughput, high-resolution techniques
are rapidly improving in speed, quality, and cost, and will soon be the norm for microbiome
Metabolites can also be measured directly using gas or liquid chromatography and mass
spectrometry to provide insight into the collective metabolic function of the gut. However,
quantitation of certain volatile metabolites requires prompt collection and acidification or ethanol
treatment of samples after collection (23). Moreover, the fecal concentration of many gut
metabolites will depend on gut transit time, cross-feeding interactions between microbes, and
rate of host absorption (24), so it is not necessarily representative of luminal concentrations.
Microbiome data analysis is typically performed using an open-source bioinformatics pipeline,
such as Quantitative Insights Into Microbial Ecology 2 (QIIME 2) (25) or Mothur (26) for 16S
and Metagenomics Reports (METAREP) (27), Metagenome Analyzer (MEGAN) (28), or
Metagenomic Rapid Annotations using Subsystems Technology (MG-RAST) (29) for
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comparative metagenomics. For 16S, sequences from samples must be de-multiplexed, quality
filtered, and clustered into operational taxonomic units (OTUs) based on sequence identity (ID)
(i.e. about 95% ID for genus; 97% ID for species). These are then taxonomically classified using
common reference databases (30,31) and visualized as a phylogenetic tree or represented using
bar plots.
The alpha ()-diversity metrics Chao1, Shannon index, and Simpson index are a measure of the
diversity within a sample and take into account both the number of unique OTUs in a sample
(richness) and the relative abundance of these OTUs (evenness). In contrast, beta ()-diversity
metrics like Bray-Curtis and UniFrac are measures of the diversity between samples. When more
than two samples are used, -diversity is calculated for every pair of samples to create a distance
(dissimilarity) matrix. The data present in the -diversity distance matrix can be visualized using
a 2-D or 3-D Principle Coordinates Analysis (PCoA) plot, where each axis explains a certain
percentage of variation present in the dataset. Each sample is represented by a single point, and
the distance between points reflects how compositionally different the samples are from one
another (32). Statistical significance of community-level differences can be assessed using a
PERMANOVA test (33).
Using these methodologies, several factors have been identified that influence gut microbial
composition and metabolic capacity beginning at birth. The fetal gut contains few if any
microbes as the womb is largely sterile (34). Microbial colonization begins at birth and is
significantly influenced by mode of delivery (vaginal or Cesarean section) and infant diet
(breastmilk or formula) (35). Other factors, including increased sanitation, reduced exposure to
infection through vaccination, elimination of entero-pathogens, and exposure to antibiotics and
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non-antibiotic drugs can also alter the commensal, or native, microbiota (36). Dietary intake also
has a significant impact on microbial composition throughout life (37).
Emerging research from our group and others suggests that exercise also influences the gut
microbiota. Over a dozen controlled animal studies have shown that exercise training
independently alters the composition and functional capacity of the gut microbiota (3851).
Matsumoto et al. (2008) was the first to find that five weeks of exercise training resulted in an
increase in the bacterial metabolite butyrate. Several other studies have recapitulated this finding
and shown that exercise training increases the relative abundance of butyrate-producing taxa
(38,41). Butyrate is a short-chain fatty acid (SCFA) produced from the bacterial fermentation of
dietary fiber. As the primary fuel for colonocytes, butyrate has been shown to increase colonic
epithelial cell proliferation, promote gut barrier integrity, and regulate the host immune system
and gene expression (52,53).
Drawing other broad conclusions as to how and to what degree exercise alters the rodent gut
microbiota has proved difficult due to incongruities in diet, species/strain, animal age, and
exercise modality used. For instance, several studies suggest that exercise increases the ratio of
Firmicutes to Bacteroidetes phyla (3840), while some studies suggest that exercise reduces this
ratio (4144). Still others have found no change at the phylum level (45,46). Several factors may
influence the disparate results observed in these studies. For instance, we recently reported that
voluntary wheel running (VWR) and forced treadmill running (FTR) the two most common
modes of endurance exercise used with rodents differentially altered the gut microbiota (47).
Mika et al. (2015) found that microbial genera were more robustly altered by VWR in juvenile,
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as compared to the adult rats (44), while Evans et al. (2014) found that VWR increased microbial
diversity, but only in mice fed a high-fat diet (41).
Evidence for a role of exercise in shaping the human gut microbiota first emerged from cross-
sectional studies (Table 1). Clarke et al. (2014) found that the gut microbiota of professional
rugby players had greater alpha diversity and a higher relative abundance of 40 different
bacterial taxa than the gut microbiota of lean sedentary controls. The athletes also had lower
abundance of Bacteroides and Lactobacillus species (spp.) than their lean sedentary counterparts
(54). More recently, Bressa et al. (2017) compared active women to sedentary controls (55) and
observed that women who performed at least three hours of exercise per week had increased
levels of Faecalibacterium prausnitzii, Roseburia hominis, and Akkermansia muciniphila. F.
prausnitzii and R. hominis are known butyrate producers (56), while A. muciniphila has been
associated with a lean BMI and improved metabolic health (57).
Several studies have also attempted to correlate the composition and metabolic capacity of the
microbiota with cardiorespiratory fitness. Durk et al. (2018) showed that a higher ratio of
Firmicutes to Bacteroidetes, the two predominant phyla in the human gut microbiota, was
significantly correlated with maximal oxygen uptake (VO2 max) (58). Estaki et al. (2016) found
that in younger adults, microbial diversity and abundance of butyrate-producing bacterial taxa
were positively correlated with cardiorespiratory fitness (59), while Barton et al. (2017) showed,
using metagenomic analyses, that athletes have altered gut microbial pathways for amino acid
biosynthesis and carbohydrate metabolism and greater fecal SCFA concentrations (60).
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Nevertheless, all of these studies were limited by their cross-sectional design and their inability
to control for the effects of diet (and perhaps other factors) on the gut microbiota. There is
considerable inter-individual variability in the composition of the microbiota, and active
individuals tend to eat differently from sedentary individuals. For instance, Clarke et al. (2014)
found that increased protein intake by elite rugby players accounted for many of the observed
differences in the gut microbiota (54). These limitations suggested the need for longitudinal
studies to determine whether exercise independently alters the gut microbiota in humans.
Recently, members of our group published findings from the first controlled longitudinal study to
assess the effects of exercise on the gut microbiome (61). In total, 32 sedentary adults (lean [BMI
<25] or obese [BMI>30]) participated in a six-week supervised endurance exercise program (30-
60 minutes duration, 3x/week) with stringent dietary controls. Several taxa were differentially
altered by exercise depending on BMI status. For instance, exercise increased Faecalibacterium
spp. in lean subjects, but reduced its abundance in obese subjects; Bacteroides spp. decreased in
the lean subjects and increased in the obese subjects. Six weeks of exercise also increased the
abundance of butyrate-producing taxa and fecal acetate and butyrate concentrations, but only in
lean subjects. Interestingly, most bacterial taxa and SCFAs that increased with exercise
subsequently decreased during the six-week sedentary washout period that followed, indicating
that the effects of exercise on the microbiota were both transient and reversible.
Similarly, Cronin et al. (2018) sought to determine whether a short-term exercise regime, with or
without whey protein supplementation, could alter gut microbial composition and function in
predominantly overweight or obese male and female adults (n=90) (62). Those randomized to the
exercise groups were required to perform moderate intensity aerobic training (18-32 minutes
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duration) and a progressive resistance training program three times per week for eight weeks.
Post-intervention assessment did not reveal any significant changes in taxonomic composition or
metabolic pathways in either exercise group compared to baseline. However, a trend was seen
for an increase in bacterial diversity in the exercise and exercise + whey protein groups,
compared to the group that received whey protein alone. Metagenomic and metabolomic
analyses revealed only modest alterations of microbial metabolism. While the study had a fairly
large sample size, the authors note that self-reported maintenance of usual dietary intake and a
wide BMI range may have prevented detection of more significant changes.
Munukka et al. (2018) performed a similar study to determine whether endurance exercise could
affect the gut metagenome in previously sedentary overweight women (n=17) (63). Six-weeks of
light to moderate intensity cycling resulted in an increased relative abundance of Akkermansia
muciniphila and a decrease in Proteobacteria. Most interestingly, only about half of the subjects‘
microbiomes responded considerably to exercise. Metagenomic analysis revealed that exercise
training decreased the abundance of several genes related to fructose and amino acid metabolism.
Together, these findings suggest that exercise has independent effects on the gut microbiota, but
longer duration or higher intensity aerobic training may be required to induce significant
taxonomic and metagenomic changes. Furthermore, the microbiota of lean individuals may be
more responsive to an exercise intervention than that of overweight or obese individuals.
There are several potential mechanisms by which exercise might alter the gut microbiota (Figure
2). The gut-associated lymphoid tissue, or GALT, lies through the small and large intestine and
contains about 70 percent of the body‘s immune cells. Several animal studies performed by
Hoffman-Goetz et al. have found that exercise alters the gene expression of intraepithelial
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lymphocytes, downregulating pro-inflammatory cytokines and upregulating anti-inflammatory
cytokines and antioxidant enzymes (6466). These immune cells reside in close proximity to
microbial communities and produce antimicrobial factors that are essential for mediating host-
microbial homeostasis (67). Similarly, exercise may impact the integrity of the gut mucus layer,
which plays important role in keeping microbes from adhering to the gut epithelium and serves
as an important substrate for certain mucosa-associated bacteria, such as Akkermansia
Exercise raises core temperature and results in heat stress, particularly when performed for long
durations or in a hot environment (68). Exercise can also reduce intestinal blood flow by more
than 50 percent, with significant gut ischemia occurring within 10 minutes of high-intensity
exercise (69). Upon rest, the splanchnic bed undergoes rapid reperfusion. While the intestine is
an anaerobic environment, gut epithelial cells primarily utilize oxidative metabolism, and high-
intensity exercise is known to transiently impair gut barrier function (69,70). Thus, exercise-
induced heat stress and ischemia may briefly result in more direct contact between the gut
mucosal immune system and the microbes that reside in the gut lumen and mucosa, with
potential consequences for gut microbial communities.
While intestinal permeability occurs briefly during acute exercise, contact between microbes and
the immune system may be reduced at rest with regular physical activity. Trained athletes have
lower levels of circulating bacterial endotoxin lipopolysaccharide (LPS) at rest than sedentary
individuals (71), and a greater heat shock protein response to heat stress (72). Increased heat
shock proteins in the gut have been shown to prevent breakdown of tight junction proteins
between epithelial cells (73). Thus, it‘s plausible that exercise represents a hormetic stressor to
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the gut that stimulates beneficial adaptations and improves the long-term resilience of the gut
Altered gut motility and/or activity of the enteric nervous system is another mechanism by which
exercise may influence the gut microbiome. Exercise reduces transit time in the large intestine
and has been shown to accelerate the movement of gas through the gastrointestinal (GI) tract
(74,75). Exercise is also well known to impact the autonomic nervous system increasing vagal
and overall sympathetic tone (76), but it‘s impact on the complex mesh-like network of neurons
that innervate the gut has not been well elucidated. Nonetheless, regional or global changes in GI
transit are likely to have profound effects on intestinal pH, mucus secretion, biofilm formation,
and availability of nutrients to microbes. Mechanical forces are also increased in the abdomen
during most forms of aerobic exercise, which could potentially influence gut motility or increase
the mixing of intestinal contents.
Exercise training may also alter the entero-hepatic circulation of bile acids. Meissner et al.
(2011) found that hypercholesterolemic mice that were given access to a running wheel for 12
weeks displayed increased bile acid secretion and increased fecal bile acid outputs compared to
hypercholesterolemic mice that remained sedentary (77). Bile acids are potent regulators of gut
microbiota community structure, and an absence of these molecules is associated with significant
alterations in gut microbial communities (i.e. gut dysbiosis) (78). Thus, changes in the bile acid
pool could significantly shift the gut microbiome with exercise.
Lastly, exercise significantly alters metabolic flux (the rate of turnover of molecules through
metabolic pathways) and requires contraction of skeletal muscle, which stimulates the release of
myokines, metabolites, and neuroendocrine hormones that may interact with the gut directly or
indirectly through a common interface with the immune system (79). Significant amounts of
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lactate are released into the blood during exercise, which could alter intestinal pH if any of this
lactate is secreted into the gut lumen. Overall, more research is needed to determine which of
these mechanisms are responsible for the adaptation of the gut microbiota to exercise training.
Exercise-induced alterations of the gut microbiota likely have implications for gut and whole-
body health. Physical activity has been shown to be protective against many chronic diseases and
offers an attractive and cost-effective way to improve quality of life (80). Though under-
recognized to date, many of these benefits may be derived via interactions with the gut
microbiota (Figure 3). Here, we discuss potential example conditions for which the gut
microbiota may play a pivotal role, though they almost certainly do not represent the full
spectrum of potential benefits. It should also be noted that in most cases the potential attribution
of beneficial effects to the gut microbiota remains speculative due to the lack of definitive data in
this area.
Colorectal cancer
Observational studies indicate that physically active individuals have a 24% reduced risk for
colorectal cancer compared to sedentary individuals (23). Beginning an exercise program after
the onset of colorectal cancer may also improve quality of life and reduce overall mortality (82).
In preclinical animal studies, VWR has been shown to reduce colon tumor incidence (83). One
mechanism for this may be increased butyrate production from exercise. Colorectal cancer
patients have been shown to have an altered gut microbiota characterized by a reduced
abundance of butyrate-producing taxa, including Roseburia and Lachnospiraceae (84).
In vitro studies have shown that butyrate differentially regulates gene expression in healthy and
cancerous cells (85). In healthy epithelial cells, butyrate is rapidly metabolized via the
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mitochondrial tricarboxylic acid (TCA) cycle. This results in a buildup of cytosolic citrate and
acetyl CoA and increases the acetylation of histones by histone acetyltransferases (HATs). This
epigenetic modification increases expression of genes involved in cell proliferation and cell
turnover, effectively strengthening the intestinal barrier (85).
In colorectal cancer cells, however, mitochondrial dysfunction results in an accumulation of
butyrate in the cytosol. Free butyrate inhibits histone deacetylases (HDACs), which results in the
epigenetic suppression of proliferation and promotion of cell death pathways (85). This may
ultimately lead to a reduction in tumor size and reduces the chance of metastasis. Indeed,
Basterfield & Mathers et al. (2010) found that Min mice, which are genetically predisposed to
intestinal adenomas, had a reduced number of large tumors in the colon and a trend towards
reduced tumor multiplicity with exercise training. There was a weak correlation between fecal
butyrate concentrations and tumor number (86).
Inflammatory bowel disease
Inflammatory bowel disease (IBD) includes both Crohn‘s disease and ulcerative colitis (UC) and
is characterized by inappropriate gut immune responses and an altered microbiota. IBD patients
have an increased relative abundance of Enterobacteriaceae and reduced abundance of
Roseburia, a genus known to produce butyrate and induce regulatory T cell formation (87).
Regulatory T cells are important for modulating the immune system, promoting tolerance to self-
antigens, preventing autoimmune disease, and dampening inflammation. Metagenomic analysis
also revealed reduced carbohydrate metabolism and amino acid biosynthesis in the fecal
microbiome of IBD patients compared to healthy controls (87) two pathways that exercise has
been reported to increase. Indeed, higher self-reported physical activity levels are associated with
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a 22 percent reduced risk of active UC (88), and a ten week intervention that included moderate
exercise improved quality of life in patients with moderately active UC (89).
Our group and others have performed several preclinical animal studies on the effects of exercise
on colitis. Szalai et al. (2014) found that six weeks of VWR increased expression of heme
oxygenase and nitric oxide synthase, increased anti-inflammatory cytokines, and reduced
inflammatory markers and the severity of mucosal damage in TNBS-induced colitis (90), while
Liu et al. (2015) found that one month of VWR suppresses pro-inflammatory cytokine
production in response to dextran sodium sulfate (DSS)-induced colitis by up-regulating
glucocorticoid-mediated peroxisome proliferator-activated receptor gamma (PPARγ)
expression in the colon (91). PPARγ regulates fatty acid storage and glucose metabolism. In
2013, members of our group confirmed that VWR conferred protection against DSS-induced
colitis and reduced disease-related symptoms and mortality, but additionally observed that FTR
exacerbated symptoms and led to higher mortality (92). Further study revealed that VWR and
FTR resulted in distinct changes in the gut microbiota (47).
To determine if exercise-induced alterations in the gut microbiota were directly responsible for
the protective effects of VWR, members of our group transferred cecal contents from exercised
or sedentary mice into naïve, sedentary germ-free mice in the first-ever ―exercise‖ fecal
microbiota transplant (FMT). When recipient mice were later subjected to an acute colitis insult
with DSS, those that had received a microbiota from exercised mice lost significantly less body
weight and had fewer clinical symptoms than those that received a microbiota from sedentary
mice. Mice receiving the microbiota from exercised mice also had a more regenerative cytokine
profile, with significantly higher levels of transforming growth factor beta (TGF-β), forkhead
box P3 (FoxP3), and interleukin (IL-22) gene expression in the distal colon (93). More studies
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are needed to determine whether exercise can beneficially modulate the gut microbiota in
humans with IBD, and whether compositional alterations parallel improvements in
Obesity and metabolic disease
Several studies have shown that the gut microbiota is closely associated with obesity and
metabolic syndrome. A seminal paper by Turnbaugh et al. (2006) showed that transplanting fecal
material from an obese mouse into a germ-free mouse resulted in rapid weight gain (94). The
obese microbiota has a significantly higher capacity for energy harvest from the diet and may
also promote intestinal permeability, allowing the influx of endotoxin into the bloodstream.
Endotoxemia itself has been shown to result in weight gain and insulin resistance (95).
Evidence from animal studies suggests that exercise may attenuate the gut dysbiosis and altered
intestinal villi morphology induced from high-fat diet feeding (45). Queipo-Ortuño et al. (2013)
found that just six days of VWR increased the relative abundance of Lactobacillus and
Bifidobacterium spp. in male rats, which were positively correlated with serum leptin levels (42),
while Lambert et al. (2015) found significant interactions between exercise and diabetic state on
the gut microbiota in an animal model of type 2 diabetes (40).
Lai et al. (2018) showed that high-fat diet fed obese mice receiving FMT from exercised,
normal-fat diet fed donor mice showed improvements in metabolic parameters, including weight
loss, reduced fasting blood glucose, and lower hepatic expression of pro-inflammatory cytokines
(96). Notably, two of the taxa that were highly associated with FMT from exercised donors,
Odoribacter and AF12 of the family Rikenellaceae, are known butyrate-producers. In animal
models of obesity, butyrate has been shown to increase energy expenditure, improve insulin
sensitivity, and reduce adiposity (97). Butyrate and other SCFAs also stimulate the production of
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satiety hormones, which help regulate food intake, and may help delay or attenuate the
development of diabetes by improving gut barrier function (98).
Mental and cognitive health
The gut microbiota has also been implicated in mental health and cognition, and the existence of
a gut-brain axis is well established (99,100). Gut microbiota-derived metabolites have been
shown to activate receptors on vagal afferents of the enteric nervous system, and certain
microbes are also capable of producing neurotransmitters; for example, Lactobacillus spp. can
produce both serotonin and gamma-aminobutyric acid (GABA) (101). Serotonin is thought to
play a role in emotion and cognitive functions, and low levels have been linked to depression.
GABA is the chief inhibitory neurotransmitter in the central nervous system and typically has
anti-anxiety and relaxant effects. Thus, it‘s no surprise that germ-free mice that lack a
commensal microbiota exhibit altered brain function, abnormal behaviors, and an exaggerated
hypothalamic-pituitary-adrenal response to stress (102).
Gut dysbiosis may also contribute to impaired mental health. Human patients with major
depressive disorder have an altered gut microbiota, characterized by changes in the relative
abundance of Firmicutes, Bacteroidetes, and Actinobacteria (103). Notably, transferring fecal
material from these patients into germ-free mice confers depression-like behaviors in the
recipient mice (103). Stevens et al. (2017) found that patients with a depressive or anxiety
disorder had a unique predicted gut metagenomic profile and increased levels of plasma markers
of intestinal permeability (104).
Exercise is well-known to have benefits for mental and neurological health (105), and it is
plausible that some of the beneficial effects of exercise on the brain are mediated by the gut
microbiota. For instance, Kang et al. (2014) found that an hour of daily wheel running increased
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the relative abundance of Lachnospiraceae, a family of known butyrate-producing microbes,
which was negatively correlated with anxiety-like behavior in adult C57Bl/6J mice (38).
Butyrate itself has been shown to upregulate brain-derived neurotrophic factor (BDNF)
expression in the hippocampus and frontal cortex of mice, which helps to support the survival of
existing neurons and encourage the formation of new neurons and synapses. Butyrate has also
been shown to regulate the activation of microglial cells, a specialized population of immune
cells in the brain (106,107). Like exercise, butyrate also appears to increase neuroplasticity and
has anti-depressant activity, boosting brain serotonin levels (108).
Overall, increasing evidence suggests that regular aerobic exercise confers benefits to the gut
microbiota, which may be partially responsible for the widespread benefits of regular physical
activity on human health. This area of research will no doubt have many exciting developments
in the coming decade, and there are many questions that are yet be answered (Figure 2). In
addition to elucidating the mechanisms involved, the effects of different forms of exercise
necessitates further study. Open questions include: What frequency, mode, or intensity of
exercise is best? How does exercise impact the gut microbiome in children or the elderly? In
healthy or diseased states? How does exercise interact with diet in shaping the gut microbiome?
Do probiotics or prebiotics influence gut responses to an exercise intervention? What about
resistance exercise?
Future research should also employ methodologies to elucidate the effects of exercise on the
microbiome in various regions of the GI tract, including microbes associated with the gut mucus
layer. While this will likely involve more invasive endoscopic procedures for human studies, it is
critical to understand the true dynamics of the gut environment. A recent study by Zmora et al.
Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
(2018) suggests that fecal samples often under- or over-represent the relative abundance of
various bacterial genera and species in the human gut (109).
While we have learned a great deal about how exercise influences bacterial communities, future
research should also seek to understand how exercise influences archaea, fungi, and viruses in
the human gut, and how exercise influences gut competition and ecological patterns. The
increasing feasibility of metagenomic studies will also help to elucidate which bioactive
metabolites produced by the gut microbiota might be most affected by exercise training.
Gnotobiotic, or germ-free, animal studies will also help to determine how exercise-induced
alterations in the gut microbiota are causally linked to alterations in disease risk. Ultimately, we
can imagine a future of personalized microbiome-based lifestyle medicine, where baseline gut
microbiota, diet, and other host factors might help predict which exercise program might be most
effective for a given individual.
Copyright © 2019 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited.
TB‘s effort toward this manuscript partially supported by grants from the National Institutes of
Health (P2CHD086851 and P30AG050886).
Funding: The authors have no funding to disclose for the preparation of this manuscript.
Conflicts of interest: The authors have no conflicts of interest to report.
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Figure 1. Methodologies commonly used to study the gut microbiome. Fecal or GI content
samples can be used for metabolite analysis or undergo chemical and mechanical digestion to
extract nucleic acids. Extracted DNA can be used for targeted genomics, shotgun sequencing, or
16S rRNA gene amplification.
Figure 2. Current unknowns and future areas of research related to exercise and the gut
microbiome. While several studies have now shown that exercise alters gut microbiota
composition, functional capacity, and metabolites, the effects of different exercise frequencies,
modes, and intensities is unknown. Assessing the effects of exercise on the gut microbiota in
different populations and its synergy with different diets also represents a key area of future
research. Mechanistic studies, such as those that utilize mice, will help determine the potential
mechanisms involved, and whether exercise-induced changes in the gut environment are
potentially disease modifying.
Figure 3. Proposed model for how exercise alters the gut microbiota and gut epithelium
with potential implications for human health. Exercise has been shown to increase butyrate-
producing taxa and fecal butyrate concentrations and reduce pro-inflammatory cytokines and
oxidative stress in the gut. Exercise is also known to have benefits on whole-body physiology,
and is protective against colon cancer, inflammatory bowel disease, depression, anxiety, and
obesity. Whether this disease protection is mediated by exercise-induced changes in the gut
microbiome and gut epithelium remains to be determined.
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Figure 1
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Figure 2
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Figure 3
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Table. Summary of cross-sectional and longitudinal studies assessing the impact of physical activity status or an exercise intervention
on the human gut microbiome.
Clarke et al,
Elite rugby players
(n=40), low BMI
controls (n=23), and
high BMI controls
Greater alpha diversity in elite
athletes compared to lean sedentary
controls. ↑Akkermansia in athletes
and low BMI controls;
↑Erysipelotrichaceae, S24-7,
Prevotella and Succinivibrio and
↓Lactobacillaceae, Bacteroides, and
Lactobacillus spp. in athletes
compared to lean controls
Estaki et al.
Healthy adults with
fitness levels (n=39)
VO2 peak accounted for more than
20 percent of the variation in species
richness. Individuals with higher
fitness had increased relative
abundance of butyrate-producing
taxa and increased fecal butyrate
Stewart et
al. 2016
Adult males Type 1
diabetics with good
glycemic control and
high levels of physical
Gut microbial composition of
patients with Type 1 diabetes in
good glycemic control and with high
physical fitness levels is comparable
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fitness (n=10) and
matched healthy adult
male controls (n=10)
to those of matche people without
Bressa et al.
women, active (>3
hours of physical
exercise/wk, n=19) or
sedentary (<30
minutes 3 days/wk,
Increased relative abundance of
Faecalibacterium prausnitzii,
Roseburia hominis, and Akkermansia
muciniphila in active women;
reduced relative abundance of
Barnesiellaceae, Odoribacteraceae
Yang et al.
women, all activity
levels, primarily
overweight or obese
Lower VO2 max was associated with
lower relative abundance of
Bacteroides spp. and higher rel.
abundance of Eubacterium rectale-
Clostridium coccoides group
Barton et al.
Professional rugby
players (n=40) and
sedentary controls
with low BMI (n=22)
or high BMI (n=24)
Rugby players had increased amino
acid and antibiotic biosynthesis,
carbohydrate metabolism, and
increased fecal SCFAs compared to
Durk et al.
Healthy young adults
(n=20 males, n=17
females) with varying
Higher ratio of Firmicutes to
Bacteroidetes was significantly
correlated with VO2 max. VO2 max
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fitness level
accounted for 22 percent of the
variance in gut microbiota
Paulsen et
al. 2017
treatment breast
cancer survivors
Received written
materials regarding
benefits of physical
activity. Fitness
measured at baseline
and 3 months
Significant association between
cardiorespiratory fitness and beta
diversity at 3 month timepoint.
Allen et al.
Previously sedentary
lean or obese adults
6 week progressive
aerobic exercise
intensity) + 6 week
sedentary washout
Several taxa were differentially
altered depending on BMI status:
Faecalibacterium increased in lean
subjects but decreased in obese;
Bacteroides decreased in lean
subjects but increased in obese.
Increased butyrate-producing taxa,
fecal acetate and butyrate
concentrations. Effects were
reversed upon return to sedentary
Cronin et al.
overweight or obese
adults randomized to
exercise-only (E),
8 week mixed
progressive moderate
aerobic exercise (18-
32 min) and
No significant changes in taxonomic
composition; trend for increase in
bacterial diversity in E and EP
groups. Only modest alterations of
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exercise + whey
protein (EP) or whey
protein only (P)
groups (n=30 each
resistance training
microbial metabolic potential.
Munukka et
al. 2018
Previously sedentary,
overweight women
6 week cycling
exercise (low-
moderate intensity)
Increased relative abundance of
Akkermansia and decreased relative
abundance of Proteobacteria. Only
half of the subjects' microbiomes
responded to exercise. Exercise
training decreased abundance of
fructose and amino acid metabolism
related genes
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... These changes can be linked to higher susceptibility to infections and the development of neurodegenerative diseases like Alzheimer's disease (Askarova et al., 2020;Bosco and Noti, 2021). Notably, a growing body of research in mice and humans shows that exercise can lead to a healthier microbiome by enhancing the number of beneficial microbes, resulting in positive effects on general health status and cognition (for reviews see Monda et al., 2017;Mailing et al., 2019). However, in humans, no RCTs on the question of whether exercise interventions influence the microbiome have been carried out so far. ...
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Introduction By 2050, the worldwide percentage of people 65 years and older is assumed to have doubled compared to current numbers. Therefore, finding ways of promoting healthy (cognitive) aging is crucial. Physical activity is considered an effective approach to counteract not only physical but also cognitive decline. However, the underlying mechanisms that drive the benefits of regular physical activity on cognitive function are not fully understood. This randomized controlled trial aims to analyze the effect of an eight-week standardized physical activity training program in older humans on cognitive, brain, and gut-barrier function as well as the relationship between the resulting changes. Methods and analysis One-hundred healthy participants aged 60 to 75 years will be recruited. First, participants will undergo an extensive baseline assessment consisting of neurocognitive tests, functional and structural brain imaging, physical fitness tests, and gut-microbiome profiling. Next, participants will be randomized into either a multi-component physical activity group (experimental condition) or a relaxation group (active control condition), with each training lasting 8 weeks and including an equal number and duration of exercises. The whole intervention will be online-based, i.e., participants will find their intervention schedule and all materials needed on the study website. After the intervention phase, participants will have their post-intervention assessment, which consists of the same measures and tests as the baseline assessment. The primary outcome of this study is the change in the cognitive parameter of visual processing speed from baseline to post-measurement, which will on average take place 10 weeks after the randomization. Secondary outcomes related to cognitive, brain, and microbiome data will be analyzed exploratory. Clinical trial registration:
... Además, el ejercicio físico puede mejorar la diversidad y la salud de la microbiota intestinal (Mailing, 2019). La microbiota intestinal es una comunidad de microorganismos, principalmente bacterias, que viven en nuestros intestinos. ...
Se realizó un estudio multidisciplinario que aborda la importancia de la actividad física en diversos contextos de salud y bienestar humano, con un enfoque particular en la inclusión de personas con discapacidades. Utilizando una combinación de teorías como la Teoría del Comportamiento Planificado y la Teoría Social Cognitiva, se exploran los vínculos entre la actividad física y los sistemas del organismo humano, las enfermedades crónicas, la salud mental, el rendimiento académico, la estética corporal, el envejecimiento saludable, la calidad de vida, y la nutrición. El método emplea una revisión exhaustiva de la literatura y un análisis crítico de las prácticas actuales. Los resultados destacan la necesidad de superar diversas barreras, como las físicas, psicológicas, y económicas, para lograr una participación inclusiva en la actividad física. Las principales conclusiones enfatizan la importancia de la colaboración comunitaria, las tecnologías y herramientas de apoyo, y las políticas inclusivas para fomentar la actividad física en todas las poblaciones.
... In children of about 3 years, gut microbiota becomes similar to that of adults, with five predominant bacterial phyla: Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Verrucomicrobia (4). Recent findings established the role of environmental factors on microbiota composition suggesting a close cross-talk between the lifestyle and the diversity of microorganisms populating the intestine (5). To date, the effects of exercise on human health have been thoroughly studied. ...
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The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren. Methods Male (114) and female children (8–10 years) belonging to five primary schools in the neighborhoods of Turin were classified as active (A) or sedentary (S) based on PAQ-C-It questionnaire. PCR amplification of salivary DNA targeted the hypervariable V3–V4 regions of the 16S rRNA bacterial genes. DADA2 workflow was used to infer the Amplicon Sequence Variants and the taxonomic assignments; the beta-diversity was obtained by PCoA with the UniFrac method; LEfSe algorithm, threshold at 5%, and Log LDA cutoff at ±0.5 were used to identify differently abundant species in A compared to S saliva sample. Daily food intake was assessed by 3-Days food record. The metabolic potential of microbial communities was assessed by PICRUSt. Results No significant differences were found in individual’s gender distribution ( p = 0.411), anthropometry, BMI ( p > 0.05), and all diet composition between A and S groups ( p > 0.05). Eight species were differently abundant: Prevotella nigrescens (LDA score = −3.76; FDR = 1.5×10–03), Collinsella aerofaciens (LDA score = −3.17; FDR = 7.45×10–03), Simonsiella muelleri (LDA score = −2.96; FDR = 2.76×10–05), Parabacteroides merdae (LDA score = −2.43; FDR = 1.3×10–02) are enriched in the A group; Gemella parahaemolysans , Prevotella aurantiaca (LDA score = −3.9; FDR = 5.27×10–04), Prevotella pallens (LDA score = 4.23; FDR = 1.93×10–02), Neisseria mucosa (LDA score = 4.43; FDR = 1.31×10–02; LDA score = 2.94; FDR = 7.45×10–03) are enriched in the S group. A prevalence of superpathway of fatty acid biosynthesis initiation ( E. coli ) and catechol degradation II (meta-cleavage pathway) was found in saliva from A compared to S children. Conclusion Our results showed that active children had an enrichment of species and genera mainly associated with a healthier profile. By contrast, the genera and the species enriched in the sedentary group could be linked to human diseases.
To improve the difficulty in wearing and uncomfortable pressure of the sports bra, shape memory polyurethane filaments (SMPUFs) were used to prepare seamless sports bras in this study. Five fabric samples with different stitch structures and yarn were prepared. Then shape memory sports bras were designed based on the properties of the different fabric samples and female body characteristics. SMPUFs were characterized by differential scanning calorimetry for the thermal properties. Shape memory properties and mechanical properties of the SMPUFs, covered yarn and fabric samples were measured. Besides this, the moisture absorbency, permeability and thermal resistance of fabrics were tested. A pressure test system was set up and the pressure of the sports bras was investigated at different temperatures. The results showed that the transition temperature ( T trans ) of the SMPUF was 27.33°C, which could be triggered by human skin temperature. The best shape fixity ratio of the fabric sample was 82.5% and the shape recovery ratio was 94.4%. The comfortable pressure of the shape memory sports bra at the mean human skin temperature of 34°C was 1.6–5.6 kPa.
The human gastrointestinal microbiota and its unique metabolites regulate a diverse array of physiological processes with substantial implications for human health and performance. Chronic exercise training positively modulates the gut microbiota and its metabolic output. The benefits of chronic exercise for the gut microbiota may be influenced by acute changes in microbial community structure and function that follow a single exercise bout (i.e., acute exercise). Thus, an improved understanding of changes in the gut microbiota that occur with acute exercise could aid in the development of evidence‐based exercise training strategies to target the gut microbiota more effectively. In this review, we provide a comprehensive summary of the existing literature on the acute and very short‐term (<3 weeks) exercise responses of the gut microbiota and faecal metabolites in humans. We conclude by highlighting gaps in the literature and providing recommendations for future research in this area. New Findings What is the topic of this review? The chronic benefits of exercise for the gut microbiota are likely influenced by acute changes in microbial community structure and function that follow a single exercise bout. This review provides a summary of the existing literature on acute exercise responses of the gut microbiota and its metabolic output in humans. What advances does it highlight? Acute aerobic exercise appears to have limited effects on diversity of the gut microbiota, variable effects on specific microbial taxa, and numerous effects on the metabolic activity of gut microbes with possible implications for host health and performance.
Recent advances in microbiome research have informed the potential role of the gut microbiota in the regulation of metabolic, cardiovascular, and renal systems, and, when altered, in the pathogenesis of various cardiometabolic disorders, including chronic kidney disease (CKD). The improved understanding of gut dysbiosis in cardiometabolic pathologies in turn has led to a vigorous quest for developing therapeutic strategies. These therapeutic strategies aim to investigate whether interventions targeting gut dysbiosis can shift the microbiota toward eubiosis and if these shifts, in turn, translate into improvements in (or prevention of) CKD and its related complications, such as premature cardiovascular disease. Existing evidence suggests that multiple interventions (eg, plant-based diets; prebiotic, probiotic, and synbiotic supplementation; constipation treatment; fecal microbiota transplantation; and intestinal dialysis) might result in favorable modulation of the gut microbiota in patients with CKD, and thereby potentially contribute to improving clinical outcomes in these patients. In this review, we summarize the current understanding of the characteristics and roles of the gut microbiota in CKD and discuss the potential of emerging gut microbiota-targeted interventions in the management of CKD.
Increasing research links the gut microbiome to neurodegenerative disorders. The gut microbiome communicates with the central nervous system via the gut–brain axis and affects behavioral and cognitive phenotypes. Dysbiosis (a dysfunctional microbiome) drives increased intestinal permeability and inflammation that can negatively affect the brain via the gut–brain axis. Healthier metabolic and lipid profiles and cognitive phenotypes are observed in individuals with more distinct microbiomes. In this review, we discuss the role of the gut microbiome and gut–brain axis in neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease and related animal models, in cancer and cancer treatments, and in metabolic syndrome. We also discuss strategies to improve the gut microbiome and ultimately brain function. Because healthier cognitive phenotypes are observed in individuals with more distinct microbiomes, increased efforts are warranted to develop therapeutic strategies for those at increased risk of developing neurological disorders and patients diagnosed with those disorders.
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Physical activity has been demonstrated to have a significant impact on gut microbial diversity and function. Emerging research has revealed certain aspects of the complex interactions between the gut, exercise, microbiota, and neurodegenerative diseases, suggesting that changes in gut microbial diversity and metabolic function may have an impact on the onset and progression of neurological conditions. This study aimed to review the current literature from several databases until 1 June 2023 (PubMed/MEDLINE, Web of Science, and Google Scholar) on the interplay between the gut, physical exercise, microbiota, and neurodegeneration. We summarized the roles of exercise and gut microbiota on neurodegeneration and identified the ways in which these are all connected. The gut–brain axis is a complex and multifaceted network that has gained considerable attention in recent years. Research indicates that gut microbiota plays vital roles in metabolic shifts during physiological or pathophysiological conditions in neurodegenerative diseases; therefore, they are closely related to maintaining overall health and well-being. Similarly, exercise has shown positive effects on brain health and cognitive function, which may reduce/delay the onset of severe neurological disorders. Exercise has been associated with various neurochemical changes, including alterations in cortisol levels, increased production of endorphins, endocannabinoids like anandamide, as well as higher levels of serotonin and dopamine. These changes have been linked to mood improvements, enhanced sleep quality, better motor control, and cognitive enhancements resulting from exercise-induced effects. However, further clinical research is necessary to evaluate changes in bacteria taxa along with age- and sex-based differences.
The human gastrointestinal tract is home to trillions of microorganisms—collectively referred to as the gut microbiome—that maintain a symbiotic relationship with their host. This diverse community of microbes grows and changes as we do, with developmental, lifestyle, and environmental factors all shaping microbiome community structure. Increasing evidence suggests this relationship is bidirectional, with the microbiome also influencing host physiological processes. For example, changes in the gut microbiome have been shown to alter neurodevelopment and have lifelong effects on the brain and behavior. Age-related changes in gut microbiome composition have also been linked to inflammatory changes in the brain, perhaps increasing susceptibility to neurological disease. Indeed, associations between gut dysbiosis and many age-related neurological diseases—including Parkinson's disease, Alzheimer's disease, multiple sclerosis, and amyotrophic lateral sclerosis—have been reported. Further, microbiome manipulation in animal models of disease highlights a potential role for the gut microbiome in disease development and progression. Although much remains unknown, these associations open up an exciting new world of therapeutic targets, potentially allowing for improved quality of life for a wide range of patient populations.
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Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.
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Recent studies suggest that exercise alters the gut microbiome. We determined whether six-weeks endurance exercise, without changing diet, affected the gut metagenome and systemic metabolites of overweight women. Previously sedentary overweight women (n = 19) underwent a six-weeks endurance exercise intervention, but two were excluded due to antibiotic therapy. The gut microbiota composition and functions were analyzed by 16S rRNA gene amplicon sequencing and metagenomics. Body composition was analyzed with DXA X-ray densitometer and serum metabolomics with NMR metabolomics. Total energy and energy-yielding nutrient intakes were analyzed from food records using Micro-Nutrica software. Serum clinical variables were determined with KONELAB instrument. Soluble Vascular Adhesion Protein 1 (VAP-1) was measured with ELISA and its' enzymatic activity as produced hydrogen peroxide. The exercise intervention was effective, as maximal power and maximum rate of oxygen consumption increased while android fat mass decreased. No changes in diet were observed. Metagenomic analysis revealed taxonomic shifts including an increase in Akkermansia and a decrease in Proteobacteria. These changes were independent of age, weight, fat % as well as energy and fiber intake. Training slightly increased Jaccard distance of genus level β-diversity. Training did not alter the enriched metagenomic pathways, which, according to Bray Curtis dissimilarity analysis, may have been due to that only half of the subjects' microbiomes responded considerably to exercise. Nevertheless, tranining decreased the abundance of several genes including those related to fructose and amino acid metabolism. These metagenomic changes, however, were not translated into major systemic metabolic changes as only two metabolites, phospholipids and cholesterol in large VLDL particles, decreased after exercise. Training also decreased the amine oxidase activity of pro-inflammatory VAP-1, whereas no changes in CRP were detected. All clinical blood variables were within normal range, yet exercise slightly increased glucose and decreased LDL and HDL. In conclusion, exercise training modified the gut microbiome without greatly affecting systemic metabolites or body composition. Based on our data and existing literature, we propose that especially Akkermansia and Proteobacteria are exercise-responsive taxa. Our results warrant the need for further studies in larger cohorts to determine whether exercise types other than endurance exercise also modify the gut metagenome.
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Aging results in chronic systemic inflammation that can alter neuroinflammation of the brain. Specifically, microglia shift to a pro-inflammatory phenotype predisposing them to hyperactivation upon stimulation by peripheral immune signals. It is proposed that certain nutrients can delay brain aging by preventing or reversing microglial hyperactivation. Butyrate, a short-chain fatty acid (SCFA) produced primarily by bacterial fermentation of fiber in the colon, has been extensively studied pharmacologically as a histone deacetylase inhibitor and serves as an attractive therapeutic candidate, as butyrate has also been shown to be anti-inflammatory and improve memory in animal models. In this study, we demonstrate that butyrate can attenuate pro-inflammatory cytokine expression in microglia in aged mice. It is still not fully understood, however, if an increase in butyrate-producing bacteria in the gut as a consequence of a diet high in soluble fiber could affect microglial activation during aging. Adult and aged mice were fed either a 1% cellulose (low fiber) or 5% inulin (high fiber) diet for 4 weeks. Findings indicate that mice fed inulin had an altered gut microbiome and increased butyrate, acetate, and total SCFA production. In addition, histological scoring of the distal colon demonstrated that aged animals on the low fiber diet had increased inflammatory infiltrate that was significantly reduced in animals consuming the high fiber diet. Furthermore, gene expression of inflammatory markers, epigenetic regulators, and the microglial sensory apparatus (i.e., the sensome) were altered by both diet and age, with aged animals exhibiting a more anti-inflammatory microglial profile on the high fiber diet. Taken together, high fiber supplementation in aging is a non-invasive strategy to increase butyrate levels, and these data suggest that an increase in butyrate through added soluble fiber such as inulin could counterbalance the age-related microbiota dysbiosis, potentially leading to neurological benefits.
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Bacteria residing in the human gastrointestinal (GI) tract has a symbiotic relationship with its host. Animal models have demonstrated a relationship between exercise and gut microbiota composition. This was the first study to explore the relationship between cardiorespiratory fitness (maximal oxygen consumption, VO2max) and relative gut microbiota composition [Firmicutes to Bacteroidetes ratio (F/B)] in healthy young adults in a free-living environment. Twenty males and 18 females (25.7±2.2 y), who did not take antibiotics in the last 6 months, volunteered for this study. VO2max was measured using a symptom-limited graded treadmill test. Relative microbiota composition was determined by analyzing DNA extracted from stool samples using Quantitative Polymerase Chain Reaction (qPCR) that specifically measured the quantity of a target gene (16s RNA) found in Firmicutes and Bacteroidetes. Relationships between F/B and potentially related dietary, anthropometric, and fitness variables were assessed using correlation analyses with appropriate Bonferroni adjustment (p<0.004). Average F/B ratio in all participants was 0.94±0.03. F/B ratio was significantly correlated to VO2max (r=0.48, p<0.003) but, no other fitness, nutritional intake, or anthropometric variables (p>0.004). VO2max explained ~22% of the variance of an individual's relative gut bacteria as determined by F/B ratio. These data support animal findings, demonstrating a relationship between relative human gut microbiota composition and cardiorespiratory fitness in healthy young adults. GI bacteria is integral in regulating a myriad of physiological processes, and greater insight regarding ramifications of exercise and nutrition on gut microbial composition may help guide therapies to promote human health.
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The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to modest but detectable changes in gut microbiota characteristics. For the first time, we show that regular whey protein intake leads to significant alterations to the composition of the gut virome.
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A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.
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The development and continuous improvement of high-throughput sequencing platforms has stimulated interest in the study of complex microbial communities. Currently, the most popular sequencing approach to study microbial community composition and dynamics is targeted 16S rRNA gene metabarcoding. To prepare samples for sequencing, there are a variety of processing steps, each with the potential to introduce bias at the data analysis stage. In this short review, key information from the literature pertaining to each processing step is described and consequently, general recommendations for future 16S rRNA gene metabarcoding experiments are made.
Empiric probiotics are commonly consumed by healthy individuals as means of life quality improvement and disease prevention. However, evidence of probiotic gut mucosal colonization efficacy remains sparse and controversial. We metagenomically characterized the murine and human mucosal-associated gastrointestinal microbiome and found it to only partially correlate with stool microbiome. A sequential invasive multi-omics measurement at baseline and during consumption of an 11-strain probiotic combination or placebo demonstrated that probiotics remain viable upon gastrointestinal passage. In colonized, but not germ-free mice, probiotics encountered a marked mucosal colonization resistance. In contrast, humans featured person-, region- and strain-specific mucosal colonization patterns, hallmarked by predictive baseline host and microbiome features, but indistinguishable by probiotics presence in stool. Consequently, probiotics induced a transient, individualized impact on mucosal community structure and gut transcriptome. Collectively, empiric probiotics supplementation may be limited in universally and persistently impacting the gut mucosa, meriting development of new personalized probiotic approaches.
Purpose: Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of six weeks of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls prior to outcome variable collection. Methods: Thirty-two lean (n=18 [9 female]) and obese (n=14 [11 female]), previously sedentary subjects participated in six weeks of supervised, endurance-based exercise training (3 days/wk) that progressed from 30 to 60 minutes/day and from moderate (60% of heart rate reserve [HRR]) to vigorous intensity (75% HRR). Subsequently, participants subsequently returned to a sedentary lifestyle activity for a six week washout period. Fecal samples were collected before and after six weeks of exercise, as well as after the sedentary washout period, with 3-day dietary controls in place prior to each collection. Results: β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short chain fatty acids (SCFAs) in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of SCFA production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. Conclusion: These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.
Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiota β-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.