Ci a ion: Bonomini-Gnu zmann, R.;
Plaza-Díaz, J.; Jo que a-Aguile a, C.;
Rod íguez-Rod íguez, A.;
Rod íguez-Rod íguez, F. E ec o
In ensi y and Du a ion o Exe cise on
Gu Mic obio a in Humans: A
Sys ema ic Re iew. In . J. En i on.
Res. Public Heal h 2022,19, 9518.
h ps://doi.o g/10.3390/ije ph
19159518
Academic Edi o : Paul B. Tchounwou
Recei ed: 15 June 2022
Accep ed: 25 July 2022
Published: 3 Augus 2022
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Copy igh : © 2022 by he au ho s.
Licensee MDPI, Basel, Swi ze land.
This a icle is an open access a icle
dis ibu ed unde he e ms and
condi ions o he C ea i e Commons
A ibu ion (CC BY) license (h ps://
c ea i ecommons.o g/licenses/by/
4.0/).
In e na ional Jou nal o
En i onmen al Resea ch
and Public Heal h
Re iew
E ec o In ensi y and Du a ion o Exe cise on Gu Mic obio a
in Humans: A Sys ema ic Re iew
Romina Bonomini-Gnu zmann 1, Julio Plaza-Díaz 2,3,4,* , Ca los Jo que a-Aguile a 1,*,
And és Rod íguez-Rod íguez 5and Fe nando Rod íguez-Rod íguez 6
1Escuela de Nu ición y Die é ica, Facul ad de Ciencias, Uni e sidad Mayo , San iago 8580745, Chile;
[email p o ec ed]
2Child en’s Hospi al o Eas e n On a io Resea ch Ins i u e, O awa, ON K1H 8L1, Canada
3Depa men o Biochemis y and Molecula Biology II, School o Pha macy, Uni e si y o G anada,
18071 G anada, Spain
4Ins i u o de In es igación Biosani a ia IBS.GRANADA, Complejo Hospi ala io Uni e si a io de G anada,
18014 G anada, Spain
5Gas ic Cance Resea ch G oup—Labo a o y o Oncology, UC Cen e o In es iga ional Oncology (CITO),
Pon i icia Uni e sidad Ca ólica de Chile, San iago 8331150, Chile; [email p o ec ed]
6IRyS G oup, Physical Educa ion School, Pon i icia Uni e sidad Ca ólica de Valpa aíso,
Valpa aíso 2374631, Chile; e nando. od iguez@puc .cl
*Co espondence: j plaza@ug .es (J.P.-D.); ca los.jo que a@mayo .cl (C.J.-A.); Tel.: +34-958241599 (J.P.-D.);
+569-95791706 (C.J.-A.)
Abs ac :
(1) Backg ound: The gu mic obio a migh play a pa in a ec ing a hle ic pe o mance and
is o conside able impo ance o a hle es. The aim o his s udy was o sea ch he ecen knowledge
o he p o agonis played by high-in ensi y and high-du a ion ae obic exe cise on gu mic obio a
composi ion in a hle es and how hese e ec s could p o ide disad an ages in spo s pe o mance.
(2) Me hods: This sys ema ic e iew ollows he PRISMA guidelines. An exhaus i e bibliog aphic
sea ch in Web o Science, PubMed, and Scopus was conduc ed conside ing he a icles published
in he las 5 yea s. The selec ed a icles we e ca ego ized acco ding o he ype o s udy. The isk o
bias was assessed using he Joanna B iggs Ins i u e’s C i ical App aisal Tool o Sys ema ic Re iews.
(3) Resul s: Thi een s udies had nega i e e ec s o ae obic exe cise on in es inal mic obio a such as
an upsu ge in I-FABP, in es inal dis ess, and changes in he gu mic obio a, such as an inc ease in
P e o ella, in es inal pe meabili y and zonulin. In con as , se en s udies obse ed posi i e e ec s o
endu ance exe cise, including an inc ease in he le el o bac e ia such as inc eased mic obial di e si y
and inc eased in es inal me aboli es. (4) Conclusions: A la ge pa o he s udies ound epo ed
ad e se e ec s on he in es inal mic obio a when pe o ming endu ance exe cises. In s udies ca ied
ou on a hle es, mo e nega i e e ec s on he mic obio a we e ound han in hose ca ied ou on
non-a hle ic subjec s.
Keywo ds: ae obic exe cise; adul s; eli e a hle es; la ge in es ine; gu mic obio a
1. In oduc ion
The in es inal o gu mic obio a is “ he se o mic obes ha colonize ou diges i e ac
ha in e ac wi h each o he and wi h he hos ” [1–3]. Cu en ly, mo e han one housand
di e en mic obial species ha e been ound ha can eside in he human gas oin es inal
ac [
4
]. App oxima ely one hund ed six y species a e ound in he la ge in es ine [
3
],
de eloping a biomass o mo e han 1.5 kg [
5
]. The mic obio a con ain bac e ia, as well as
ungi, i uses, and p o is s [
1
]. The mos abundan and di e se amilies o bac e ia in he
adul gas oin es inal ac a e Ac inobac e ia,Bac e oide es,Fi micu es, and P o eobac e ia,
and less di e se a e Ve ucomic obia,Len isphae ae,Sine gis e es,Planc omyce es,Tene icu es,
and Deinococcus-The mus [2,3].
In . J. En i on. Res. Public Heal h 2022,19, 9518. h ps://doi.o g/10.3390/ije ph19159518 h ps://www.mdpi.com/jou nal/ije ph
In . J. En i on. Res. Public Heal h 2022,19, 9518 2 o 17
The composi ion o he gu mic obio a is o med h oughou ea ly childhood, induced
by gene ic and en i onmen al ac o s [
1
–
3
]. The ma u a ion o he in es inal mic obio a
in he adul ype is gone a he age o h ee yea s [
1
,
6
]. Fac o s such as age, li es yle, die ,
and gene ics can al e he gu mic obio a, c ea ing a dynamic ecosys em [
7
]. O he ela ed
ac o s could include mode o deli e y, geog aphy, b eas eeding, weaning, and exposu e
o en i onmen al bac e ia [
1
]. Some esea che s p oposed ha he in es inal mic obio a can
ac as an endoc ine o gan [
8
] and can ha e an eno mous impac on human heal h, including
he immune unc ion, physiology, me abolism, and nu i ion o he hos [
9
]. In he same
line, he gu mic obio a pe o ms a se ies o p o ec i e, s uc u al, and me abolic unc ions
essen ial o he heal h o he hos , including ood handling, he inges ion o complex
polysaccha ides no diges ible by he hos , he mo emen o pa hogens, and he syn hesis
o i amins among o he s [
10
]. Obse a ional s udies ha e ound ha in es inal mic obio a
may con ibu e ei he o he pa hogenesis o a ious common me abolic diso de s including
ype 2 diabe es, obesi y, ca dio-me abolic diseases, malnu i ion, and non-alcoholic li e
disease, as well as o he me abolic heal h o he human hos [
11
]. Heal hy gu mic obio a
shows an essen ial ole in he con igu a ion o he local and sys emic immune unc ion o
in es inal bac e ia h oughou li e, a o ing he main enance o ole ance owa d an igens
o he commensals and ac i a ion agains an igens o commensal pa hogens [
12
]. The
in es inal mic obio a plays an impo an ole in he egula ion o hos ene gy me abolism,
hyd a ion s a us, sys emic in lamma o y esponses, and oxida i e s ess [13].
Physical exe cise is desc ibed as he implemen a ion o some ac i i y in o de o
imp o e o p ese e o e all heal h and physical i ness [
14
,
15
]. Cu en ly, physical exe cise
is ecognized as a o midable p e en i e and ea men media ion ha is ecognized o be
e icien in causing bene i s o immune and me abolic heal h [
15
,
16
]. Endu ance exe cise
is desc ibed as ca dio ascula ac i i y, o example: cycling, unning, swimming, skiing,
and owing ha is pe o med o a long ime, ou o six hou s pe day, six days pe
week [
17
]. This in ense exe cise includes p ocesses ha in ol e physiological, a ec i e,
cogni i e–beha io al, and biochemical esponses in an e o o eco e homeos asis [9].
Some p o essional a hle es expe ience immunosupp ession o gas oin es inal symp-
oms, such as abdominal pain, dia hea, o leaky gu synd ome [
8
]. Al e a ions in he
in es inal mic obio a p oduced by s enuous exe cise can also p oduce exe cise-induced
gas oin es inal diso de s [
18
]. Some symp oms ha a e s a ed du ing he pe o mance o
endu ance exe cise include bloa ing, nausea, c amps, and dia hea [
19
]. I has been s udied
ha exe cising o exhaus ion can dis up he balance among he gu mic obio a and he
immune sys em [
12
]. Exe cise-induced gas oin es inal damage o in lamma ion could
ad e sely a ec a hle ic ou ine and, in some cases, ha e compe i ion d opou [
20
]. An-
o he s udy men ions ha in ense exe cise c ea es inc eased gas oin es inal damage, mild
endo oxemia, and in es inal pe meabili y [21]. The main inding in pos -exe cise gas oin-
es inal p oblems is possible ischemia– epe usion inju y de eloping om a momen a y
in e up ion o splanchnic blood low. When he in ense physical exe cise inishes, we ob-
se ed igge ing eac i e oxygen species (ROS) p oduc ion, damage o he gas oin es inal
mucosa, and in lamma ion [22].
Likewise, i is li le known hus a how high-in ensi y exe cise in luences he in es inal
mic obio a [
21
]. The impo ance o knowing he mechanisms in which he in es inal
mic obio a migh ha e an impo an ole in a ec ing a hle ic ou ine is o signi ican
a en ion o a hle es wo king o expand hei compe i i e pe o mance and diminish
ecupe a ion ime du ing aining [
12
]. Such in o ma ion could ha e an ad an age in he
comp ehension o gu mic obio a in luences on a hle e heal h [12].
The e o e, he main aim o his sys ema ic e iew is o elucida e he knowledge o
he unc ion played by high-in ensi y and high-du a ion ae obic exe cise on gu mic o-
bio a composi ion in a hle es and how hese e ec s could p o ide disad an ages in hei
spo s pe o mance.
In . J. En i on. Res. Public Heal h 2022,19, 9518 3 o 17
2. Ma e ials and Me hods
2.1. Sea ch S a egy
This sys ema ic e iew ollows he PRISMA guidelines [
23
]. An exhaus i e biblio-
g aphic sea ch o h ee da abases (Web o Science, PubMed, and Scopus) was conduc ed
conside ing he a icles published in he las 7 yea s ( om 1 Janua y 2015 o 31 Augus 2021).
Table 1shows he sea ch s a egy in he Web o Science, PubMed, and Scopus da abases.
This sys ema ic e iew was lis ed on he PROSPERO (In e na ional p ospec i e egis e o
sys ema ic e iews) websi e on 5 May 2022, wi h he ollowing eco d CRD42022323300.
A ailable om: h ps://www.c d.yo k.ac.uk/p ospe o/display_ eco d.php?ID=CRD420
22323300 (accessed on 14 June 2022).
Table 1. Sea ch s a egy in da abases.
Da abase Sea ch S a egy Limi s Fil e s
Web o Science
(ALL (Physical ac i i y AND gu mic obio a OR Physical
ac i i y AND in es inal ba ie OR Physical ac i i y AND
in es inal pe meabili y OR Physical exe cise AND gu
mic obio a OR Physical exe cise AND in es inal ba ie OR
Physical exe cise AND in es inal pe meabili y))
Ti le
A icles
English
238 i ems il e ed
PubMed
(Physical ac i i y OR physical exe cise) AND (gu mic obio a
OR in es inal ba ie OR in es inal pe meabili y)
Ti le
A icles
English
Humans
104 i ems il e ed
Scopus
TITLE-ABS-KEY (physical AND ac i i y AND gu AND
mic obio a) OR (physical AND ac i i y AND in es inal AND
ba ie ) OR (physical AND ac i i y AND in es inal AND
pe meabili y) OR (physical AND exe cise AND gu AND
mic obio a) OR (physical AND exe cise AND in es inal AND
ba ie ) OR (physical AND exe cise AND in es inal AND
pe meabili y) AND (LIMIT-TO (OA, “all”)) AND (LIMIT-TO
(PUBYEAR, 2022) OR LIMIT-TO (PUBYEAR, 2021) OR
LIMIT-TO (PUBYEAR, 2020) OR LIMIT-TO (PUBYEAR, 2019)
OR LIMIT-TO (PUBYEAR, 2018) OR LIMIT-TO (PUBYEAR,
2017) OR LIMIT-TO (PUBYEAR, 2016) OR LIMIT-TO
(PUBYEAR, 2015)) AND (LIMIT-TO (DOCTYPE, “a ”)) AND
(LIMIT-TO (LANGUAGE, “English”))
Ti le
A icles
English
5934 i ems il e ed
2.2. Selec ion and Exclusion C i e ia
The selec ion c i e ia we e: (i) a icles w i en in English, (ii) da abases a o emen ioned,
(iii) human s udies, (i ) o iginal a icles: clinical ials, andomized con olled ials (RCTs)
quasi-expe imen al, long- e m, p ospec i e, and c oss-sec ional s udies, ( ) a icles om
Janua y 2015 o Augus 2021. The exclusion c i e ia we e: (i) s udies ha include people
wi h pa hologies, (ii) s udies ha include animals, (iii) s udies ha comp ise child en unde
18 yea s o age and olde adul s (+65 yea s), (i ) s udies ha in e ened wi h supplemen s
o some die , ( ) case s udies, case epo s, le e s o he edi o , sys ema ic e iew and
me a-analyses and na a i e e iew. No es ic ions we e placed on he body composi ion
o he ained subjec .
A e emo ing epea ed documen s, sui abili y was measu ed by e alua ion o he
manusc ip i le and abs ac and la e e alua ion o he ull ex .
2.3. Da a Ex ac ion and Reliabili y
The sea ch was ca ied ou by i e independen e iewe s (R.B.-G., F.R.-R., J.P.-D.,
C.J.-A.
and A.R.-R.). They ead he i les and abs ac s o all e ie ed a icles. A mee ing
was held o esol e disag eemen s abou eligibili y. The ollowing in o ma ion was collec ed
om each included s udy: he i s au ho , yea o publica ion, ype o s udy, objec i e,
he numbe o subjec s, body mass index (BMI), maximum oxygen consump ion (VO
2max
),
In . J. En i on. Res. Public Heal h 2022,19, 9518 4 o 17
gende , and age when i was a ailable, ype o exe cise, how he exe cise was ca ied
ou , he molecula analysis used o he de ec ion o he gu mic obio a, he main esul s
ob ained, and conclusions.
The selec ed a icles we e ca ego ized acco ding o he ype o s udy (low-, medium-,
o high-in ensi y o long- e m exe cise in e en ions). The esul s o he s udies ha me
he selec ion c i e ia o hei eco e y we e examined.
2.4. Assessmen o he Quali y and Le el o E idence
The isk o bias was assessed using he Joanna B iggs Ins i u e’s C i ical App aisal Tool
o Sys ema ic Re iews. In summa y, his ool includes ou speci ic checklis s depending
on he s udy design (i.e., c oss-sec ional, quasi-expe imen al, coho , RCTs s udies). The
answe s o each o hem had ou possible ca ego ies: “yes” (c i e ion me ) and “no”
(c i e ion no me ). Speci ic ools included: eigh i ems o c oss-sec ional s udies, nine
i ems o quasi-expe imen al, and hi een i ems o RCTs. Acco ding o he abo e, he
s udies we e conside ed as “low quali y” e idence when
≤
49% o he i ems we e classi ied
as “yes” (c i e ion me ). Following, he a icles we e conside ed as “medium quali y”
e idence be ween 50–74% o he i ems we e sco ed as “yes” and “high quali y” e idence
when
≥
75% o he i ems we e classi ied as “yes”. The answe s “no applicable” and “non-
clea ” we e excluded by pe cen age [
24
–
26
]. The i e e iewe s assessed he s udies’ quali y
sepa a ely. A consensus mee ing was o ganized o esol e possible di e ences be ween
he e iewe s.
3. Resul s
Figu e 1displays he chosen epo ing elemen s o sys ema ic e iews and he low
cha o he sea ch s a egy. A o al o 6277 s udies we e loca ed in he h ee da abases
assessed. Then, 95 s udies we e excluded o duplica es and 6136 s udies we e excluded
a e eading he i le and abs ac ha we e ou side he opic o he e iew. A o al o
45 s udies we e assessed o eligibili y. A e analyzing he exclusion c i e ia, six een
s udies we e included. Se en s udies had an obse a ional design (i.e., i e c oss-sec ional
and wo long- e m designs), and nine s udies had an expe imen al design (eigh we e
quasi-expe imen al, and one was RCT).
Table 2shows he summa y o he s udies included. This e iew is ocused on da a
om 513 pa icipan s, and he sample size anged om 4 o 86 subjec s. Two o he six een
s udies in ol ed only women [
18
,
27
], six in ol ed only men [
5
,
13
,
16
,
28
–
30
], i e in ol ed
bo h men and women [
7
,
9
,
22
,
31
,
32
] and h ee s udies did no epo he sex o he sub-
jec s [
19
,
33
,
34
]. The age o he subjec s anged om 18 and 49 yea s; wo s udies did no
epo he age o he subjec s [
28
,
33
]. The samples we e om 10 di e en coun ies: h ee
s udies we e led in Poland, wo in Spain, wo in he Uni ed S a es, wo in China, wo in
I eland, one in he Uni ed Kingdom, one in Aus alia, one in Belgium, one in Ge many and
one om Japan.
Rega ding he cha ac e is ics o he sample, ele en s udies o he six een we e con-
duc ed on endu ance a hle es ( unne s, cyclis s, and ia hle es). Among hese nine s udies
conside ing medium- and long-dis ance unne s [
5
,
13
,
16
,
18
,
22
,
29
,
30
,
32
,
33
], h ee s udies
inco po a ed physically ac i e subjec s [
27
,
31
,
34
], one s udy on ia hle es [
19
], a s udy
on cyclis s [
7
], a s udy included ma ial a s p o essionals [
9
], and a s udy on ugby play-
e s [
28
]. Mos o he s udies inco po a ed in his sys ema ic e iew (81%) used ecal samples
o de e mine changes in he in es inal mic obio a. O hese, mainly 75% de e mined he 16S
ibosomal RNA gene ic sequence ha is commonly used o iden i ica ion, classi ica ion,
and quan i a ion o mic obes wi hin complex biological mix u es such as en i onmen al
samples and in es inal samples. A mino i y o ou s udies (25%) used plasma samples
h ough he p o ein enzyme-linked immunoso ben assay es o de e mine ma ke s such
as in es inal a y-acid binding p o ein (I-FABP) ela ed o mucosal damage, zonulin associ-
a ed wi h in es inal pe meabili y, and co isol, c- eac i e p o ein, and TNF-
α
ela ed o a
p oin lamma o y s a us.
In . J. En i on. Res. Public Heal h 2022,19, 9518 5 o 17
In . J. En i on. Res. Public Heal h 2022, 19, x 5 o 18
Figu e 1. Flowcha o a icles h ough he sea ch p ocess.
Table 2 shows he summa y o he s udies included. This e iew is ocused on da a
om 513 pa icipan s, and he sample size anged om 4 o 86 subjec s. Two o he six een
s udies in ol ed only women [18,27], six in ol ed only men [5,13,16,28–30], i e in ol ed
bo h men and women [7,9,22,31,32] and h ee s udies did no epo he sex o he subjec s
[19,33,34]. The age o he subjec s anged om 18 and 49 yea s; wo s udies did no epo
he age o he subjec s [28,33]. The samples we e om 10 di e en coun ies: h ee s udies
we e led in Poland, wo in Spain, wo in he Uni ed S a es, wo in China, wo in I eland,
one in he Uni ed Kingdom, one in Aus alia, one in Belgium, one in Ge many and one
om Japan.
Rega ding he cha ac e is ics o he sample, ele en s udies o he six een we e con-
duc ed on endu ance a hle es ( unne s, cyclis s, and ia hle es). Among hese nine s udies
conside ing medium- and long-dis ance unne s [5,13,16,18,22,29,30,32,33], h ee s udies
inco po a ed physically ac i e subjec s [27,31,34], one s udy on ia hle es [19], a s udy on
cyclis s [7], a s udy included ma ial a s p o essionals [9], and a s udy on ugby playe s
[28]. Mos o he s udies inco po a ed in his sys ema ic e iew (81%) used ecal samples
o de e mine changes in he in es inal mic obio a. O hese, mainly 75% de e mined he
16S ibosomal RNA gene ic sequence ha is commonly used o iden i ica ion, classi ica-
ion, and quan i a ion o mic obes wi hin complex biological mix u es such as en i on-
men al samples and in es inal samples. A mino i y o ou s udies (25%) used plasma
samples h ough he p o ein enzyme-linked immunoso ben assay es o de e mine
ma ke s such as in es inal a y-acid binding p o ein (I-FABP) ela ed o mucosal damage,
zonulin associa ed wi h in es inal pe meabili y, and co isol, c- eac i e p o ein, and TNF-
α ela ed o a p oin lamma o y s a us.
Figu e 1. Flowcha o a icles h ough he sea ch p ocess.
The esul s e ealed ha nine s udies showed nega i e e ec s o ae obic exe cise on
he in es inal mic obio a. Among hese ad e se e ec s, h ee s udies ound an inc ease in
I-FABP [
5
,
16
,
29
], one s udy p esen ed in es inal dis ess [
5
], h ee s udies obse ed nega i e
changes in he mic obiome [
30
–
32
], wo s udies ound an inc ease in P e o ella [
7
,
33
], h ee
s udies obse ed an inc ease in in es inal pe meabili y [
16
,
19
,
29
], and wo s udies epo ed
an inc ease in zonulin [
19
,
29
]. In con as , se en s udies obse ed posi i e e ec s o en-
du ance exe cise, including an inc ease in he le el o bac e ia such as Rosebu ia hominis,
Bi idobac e ium spp., Akke mansia muciniphila,Faecalibac e ium p ausni zii [
18
,
27
], Co iobac e i-
aceae [22], inc eased mic obial di e si y [9,13,33] and inc eased in es inal me aboli es [28].
Addi ionally, an analysis has been pe o med o de e mine he s udy quali ies included
in his e iew. Fo his, he Joanna B iggs Ins i u e’s c i e ium checklis (Table 3) was
used. Di e en c i e ia we e used acco ding o he cha ac e is ics o he s udies. In his
ega d, one s udy ul illed 100% o he c i e ia [
27
], and se en s udies ul illed
≥
75% o he
quali y c i e ia [
7
,
9
,
13
,
27
,
28
,
31
,
33
], classi ying hemsel es as high quali y. The es o he
s udies [
5
,
16
,
18
,
19
,
22
,
29
,
30
,
32
,
34
] we e classi ied as medium quali y because hey ob ained
a alue be ween >50% and <75% o he c i e ia (among 50–69.2%). No s udies wi h low
quali y we e ound (<50% o he c i e ia).

In . J. En i on. Res. Public Heal h 2022,19, 9518 6 o 17
Table 2. Cha ac e is ics as he ype o s udy, aim, sample, design, and mean esul s o he s udies.
Au ho , Yea Type o S udy AIM Sample S udy Design Resul s
Pugh e al. (2017) [5] Quasi-Expe imen al
Cha ac e ize he HIIT
e ec s on small in es inal
damage ma ke s
n= 11 (men unne s ained)
Aged 33.1 ±10.4; VO2max
60.0 ±3.2 mL/kg/min
Acu e HIIT episode ma ke s o
in es inal pe meabili y and damage
we e e alua ed and compa ed wi h
es ing condi ions. Minimum
unning pe o mance o 10 km
(39 min) and a minimum o
5 wo kou sessions pe week, using
se um sampling, p e-exe cise, a e
each se o exe cises,
and 2 h pos -baseline
HIIT signi ican ly inc eased he
se um lac ulose: hamnose a io and
suc ose concen a ions compa ed
wi h es . In con as , u ina y
lac ulose: hamnose o suc ose
concen a ions did no a y be ween
s udy g oups. Plasma I-FABP
augmen ed in he ecupe a ion
pe iod om HIIT only. A e 24 h o
HIIT, he esea che s ound mild
symp oms o GI dis ess
Liang e al. (2019) [9] C oss-sec ional
Whe he
he in es inal mic obio a is
dis inc i e be ween
highe -le el and
lowe -le el a hle es
n= 31 (p o essional ma ial
a s a hle es).
15 women and 16 men;
aged 20–24
Ma ial a s a hle es; Wushu ou ine,
igo ous, as and dynamic spo s.
The esea che s used 16S RNA gene
sequencing o de e mine he
in es inal changes
Highe -le el a hle es ha e
augmen ed me abolic capaci y and
di e si y in he in es inal mic obio a
compa ed wi h lowe -le el a hle es.
Pe e sen e al. (2017) [7] C oss-sec ional
De e mine he p esence o
dis inc i e o ganisms in
p o essional and ama eu
le el compe i i e cyclis s
n = 33 (p o essional and
ama eu le el compe i i e
cyclis s); 11 women and
22 men; aged 19–49
The s udy used me a ansc ip omic
(RNA-Seq) sequencing and mWGS
The inc ease in P e o ella was
associa ed wi h ime epo ed
exe cising du ing an a e age week.
Se e al p o essional cyclis s ha e
augmen ed le els o
Me hanob e ibac e smi hii ansc ip s
compa ed wi h ama eu cyclis s.
B essa e al. (2017) [27] C oss-sec ional
Compa e in es inal
composi ion among wo
g oups di ided by physical
exe cise le els
n= 40
(p emenopausal women).
19 ac i e and 21 seden a y
Aged 18–40;
BMI 20–25 kg/m2
The esea che s used 16S RNA gene
sequencing o de e mine he
in es inal changes
Pe o mance o physical ac i i y was
associa ed wi h he p esence o
heal h-p omo ing bac e ia
(R. hominis,A. muciniphila,
Bi idobac e ium spp., and
F. p ausni zii). Dec eased le els o
di e si y we e co ela ed wi h
seden a y pa ame e s
In . J. En i on. Res. Public Heal h 2022,19, 9518 7 o 17
Table 2. Con .
Au ho , Yea Type o S udy AIM Sample S udy Design Resul s
Ka hu e al. (2017) [16] Quasi-expe imen al
E alua e he e ec o
unning on GI
unc ion ma ke s
n= 17 (ac i e unne s);
8 women and 9 men;
aged 18–45
The esea che s measu ed seconda y
a iables, such as zonulin, le els o
se um in es inal I-FABP, and
bac e ial LPS, among o he s
Bo h, se um I-FABP and in es inal
pe meabili y inc eased a e unning,
wi hou di e ences amongs g oups.
No changes we e obse ed in he
bac e ial LPS in se um
Keohane e al.
(2019) [13]Long- e m
Analyze he changes in he
in es inal mic obio a o ou
well- ained male a hle es
o p olonged, high-in ensi y
ans-oceanic owing
n= 4 (men a hle es
ansa lan ic owing). Aged
25–27; BMI 23–25 kg/m2;
VO2Max 46–50 mL/kg/min
Me agenomic whole-genome
sho gun sequencing was used
In ense exe cise clea ly impac s he
di e si y o he in es inal mic obio a,
wi h changes in speci ic bac e ia
ela ed o me abolic pa hways
Bycu a e al. (2021) [31] Quasi-expe imen al Impac o CRE o RTE on
in es inal mic obio a
n= 56
n= 28 CRE g oup
(21 women; Aged 20.7; BMI
24.5 kg/m2and 7 men; aged
20; BMI 24.0 kg/m2.n= 28
RTE g oup (17 women; aged
20.4; BMI 23.2 kg/m2and
11 men; aged 22.6; BMI
24.59 kg/m2
In es inal mic obio a was measu ed
using 16S RNA gene sequencing
The obse ed changes we e
associa ed only wi h he CRE g oup,
esul ing in dis u bance o he
in es inal mic obio a
Mo ishima e al.
(2020) [18]C oss-sec ional
E ec s o
highly in ensi e endu ance
exe cise on he in es inal
mic obio a and i s
ela ionship wi h he onse
o he exe cise-induced
GI diso de s
n= 29 (15 women Japanese
endu ance unne s and
14 nona hle ic bu
heal hy women).
Aged 20–21;
BMI 20.7–21.9 kg/m2
Fecal mic obio a was es ed using
16S RNA me agenomics, and o he
a iables such as mois u e con en ,
o ganic acids, and pu e ac i e
me aboli es concen a ions
we e examined
Female eli e endu ance unne s ha e
mo e abundance o Faecalibac e ium,
and hese changes could be
associa ed wi h he succina e
concen a ion in his g oup
To a e al. (2019) [19] Long- e m
E alua e in es inal and
muscle damage
in ia hle es
n= 15 ( ia hle es).
Aged 6–14;
VO2max
58.8 ±4.5 mL/kg/min
Va iables used o he analysis we e:
co isol, c- eac i e p o ein, zonulin,
and TNF-α
Zonulin and a iables o
pe meabili y we e augmen ed a e
he ace
In . J. En i on. Res. Public Heal h 2022,19, 9518 8 o 17
Table 2. Con .
Au ho , Yea Type o S udy AIM Sample S udy Design Resul s
Zhao e al. (2018) [22] Quasi-expe imen al
The gu mic obio a
immedia ely esponds o
he en e ic changes
in ama eu
hal -ma a hon unne s
n= 20 (4 women and 16 men
ama eu
hal -ma a hon unne s).
Aged 31.3;
BMI 22.6 kg/m2
Fecal samples we e analyzed be o e
and a e he ma a hon using 16
DNA sequencing analyses
Co iobac e iaceae changes we e
ela ed o he exe cise ole in
a oiding disease and e ining
heal h ou comes.
Moi inho-Sil a e al.
(2021) [34]
Randomized
con olled ial
Analyze he changes in he
in es inal mic obio a on
p e iously physically
inac i e, heal hy adul s in
compa ison o con ols ha
did no pe o m
egula exe cise
n= 36 (11 con ols;
13 endu ance g oup;
12 s eng h g oup). Aged
22–41.3; BMI 19.7–32.5 kg/m
2
Fecal mic obio a was es ed using
16S RNA me agenomics
Mucosal damage and in lamma ion
we e ound a e sho - e m
esis ance aining. No changes we e
obse ed in in es inal mic obio a
Sadowska-K epa e al.
(2021) [29]Quasi-expe imen al
E alua e in es inal damage
in middle-aged
male subjec s
n= 10 (ama eu
long-dis ance unne s).
Aged 21–35
Va iables used o he analysis we e:
TAS, TOS/TOC, hs-CRP, I-FABP,
and zonulin
A e he exe cise, he le els o
in es inal pe meabili y bioma ke s
as, hs-CRP, I-FABP, zonulin, and
in lamma ion we e augmen ed
Kulecka e al.
(2020) [33]Quasi-expe imen al
E alua e di e ences in
in es inal mic obio a
amongs heal hy con ols
and endu ance a hle es
n= 71
n= 14 ma a hon unne s;
n= 11 c oss-coun y skie s;
n= 46 heal hy
con ol indi iduals
Fecal mic obio a was es ed using
16S RNA me agenomics
Excessi e aining is associa ed wi h
changes in Bac e oides and P e o ella
and bac e ial di e si y
Tabone e al. (2021) [30] Quasi-expe imen al
De e mine whe he he
changes a e d i en
by exe cise
on he gu mic obio a (wi h
16S RNA gene) and he
se um and
ecal me abolome
n= 40 (men endu ance
c oss-coun y unne s).
Aged 35.8 ±8.0; BMI
22.8 ±2.1 kg/m2; VO2max
58.8 ±3.24 mL/kg/min
Fecal mic obio a was es ed using
16S RNA me agenomics
The changes in gu mic obio a could
be ela ed o physiological changes
in ammonia, u ic acid, and lac a e
In . J. En i on. Res. Public Heal h 2022,19, 9518 9 o 17
Table 2. Con .
Au ho , Yea Type o S udy AIM Sample S udy Design Resul s
Ba on e al. (2017) [28] C oss-Sec ional
E alua e di e ences in
in es inal mic obio a
amongs
exe cise and a mo e
seden a y s a e
n= 86 (40 men p o essional
in e na ional ugby union
playe s and 46 men con ols)
Fecal mic obio a was es ed using
16S RNA me agenomics
P o essional in e na ional ugby
union playe s had mo e a o able
e ec s in me abolic pa hways han
he con ol g oup
C a en e al. (2021) [32] Quasi-expe imen al
E alua e di e ences in
in es inal mic obio a
acco ding o
aining olume
n= 14 (highly ained
middle-dis ance unne s).
n= 6 women; aged 22.0
±
3.4;
VO2max
59.0 ±3.2 mL/kg/min
n= 8 men; aged 20.7 ±3.2;
VO2max
70.1 ±4.3 mL/kg/min
Fecal mic obio a was es ed using
16S RNA me agenomics
No changes we e obse ed in
in es inal mic obio a acco ding o
aining olume in uppe axons.
Changes in amily, genus, and
species we e obse ed, hese changes
did no e u n o p e-le els
Abb e ia ions: AFT, a e ecal; BEF, be o e ecal; BMI, body mass index; CRE, ca dio espi a o y exe cise; DS, s anda d de ia ion; FCCS, emale c oss-coun y skie s; FDR, alse disco e y
a e; FMR, emale ma a hon unne s; GI, gas oin es inal; HIIT, high-in ensi y in e al aining; hs-CRP, High-sensi i i y C- eac i e p o ein; H olT , high- olume aining; I-FABP,
in es inal a y acid-binding p o ein; kg/m
2
, kilog am pe squa e me e ; LPS, lipopolysaccha ide; MCCS, male c oss-coun y skie s; MCHC, mean co puscula hemoglobin concen a ion;
mL/kg/min, millili e s pe minu e pe kilog am; MMR, male ma a hon unne s; mWGS, me agenomic whole genome sho gun; No mT no mal aining; PGM, pe sonal genome
machine; PWC, physical wo king capaci y; RNA, ibosomal ibonucleic acid; RTE, esis ance aining exe cise; Tape T , exponen ial educ ion in aining; TAS, o al an ioxidan s a us;
TOC, o al oxidan capaci y; TOS, o al oxidan s a us; VO2max, he maximum amoun o oxygen; WHO, Wo ld Heal h O ganiza ion; WSER, Wes e n S a es Endu ance Run.
In . J. En i on. Res. Public Heal h 2022,19, 9518 16 o 17
50.
Ca aldi, S.; Bona olon à, V.; Poli, L.; Clemen e, F.M.; De Candia, M.; Ca u o, R.; Sil a, A.F.; Badicu, G.; G eco, G.; Fische i, F.
The Rela ionship be ween Physical Ac i i y, Physical Exe cise, and Human Gu Mic obio a in Heal hy and Unheal hy Subjec s:
A Sys ema ic Re iew. Biology 2022,11, 479. [C ossRe ]
51.
Ley, R.E. Gu mic obio a in 2015: P e o ella in he gu : Choose ca e ully. Na . Re . Gas oen e ol. Hepa ol.
2016
,13, 69–70.
[C ossRe ] [PubMed]
52.
Ko a che a-Da cha y, P.; Nilsson, A.; Ak ami, R.; Lee, Y.S.; De Vadde , F.; A o a, T.; Hallen, A.; Ma ens, E.; Bjö ck, I.; Bäckhed, F.
Die a y Fibe -Induced Imp o emen in Glucose Me abolism Is Associa ed wi h Inc eased Abundance o P e o ella. Cell Me ab.
2015,22, 971–982. [C ossRe ]
53.
Liu, H.; Zhang, H.; Wang, X.; Yu, X.; Hu, C.; Zhang, X. The amily Co iobac e iaceae is a po en ial con ibu o o he bene icial
e ec s o Roux-en-Y gas ic bypass on ype 2 diabe es. Su g. Obes. Rela . Dis. 2018,14, 584–593. [C ossRe ] [PubMed]
54.
Ribei o, F.M.; Pe iz, B.; Ma ques, G.; Kamilla, L.H.; F anco, O.L. Is The e an Exe cise-In ensi y Th eshold Capable o A oiding
he Leaky Gu ? F on . Nu . 2021,8, 627289. [C ossRe ] [PubMed]
55.
Yücel, G.; Zhao, Z.; El-Ba awy, I.; Lan, H.; Lang, S.; Li, X.; Buljubasic, F.; Zimme mann, W.-H.; Cyganek, L.; U ikal, J.; e al.
Lipopolysaccha ides induced in lamma o y esponses and elec ophysiological dys unc ions in human-induced plu ipo en s em
cell de i ed ca diomyocy es. Sci. Rep. 2017,7, 2935. [C ossRe ] [PubMed]
56.
Ngkelo, A.; Meja, K.; Yeadon, M.; Adcock, I.; Ki kham, P.A. LPS induced in lamma o y esponses in human pe iphe al blood
mononuclea cells is media ed h ough NOX4 and Giαdependen PI-3kinase signalling. J. In lamm. 2012,9, 1. [C ossRe ]
57.
Ped inolla, A.; Ven u elli, M.; Ki mizi, E.; Mosche a, F.; Za dini, M.; Rudi, D.; Bacchi, E.; Schena, F.; Moghe i, P.; Lanza, M.
Role o Exe cise in Vascula Func ion and In lamma o y P o ile in Age-Rela ed Obesi y. J. Immunol. Res.
2018
,2018, 7134235.
[C ossRe ] [PubMed]
58.
Robe s, J.D.; Suckling, C.A.; Peedle, G.Y.; Mu phy, J.A.; Dawkins, T.G.; Robe s, M.G. An Explo a o y In es iga ion o Endo oxin
Le els in No ice Long Dis ance T ia hle es, and he E ec s o a Mul i-S ain P obio ic/P ebio ic, An ioxidan In e en ion.
Nu ien s 2016,8, 733. [C ossRe ]
59.
Sil a, J.S.; Segu o, C.S.; Na es, M.M.V. Gu mic obio a and physical exe cise in obesi y and diabe es—A sys ema ic e iew.
Nu . Me ab. Ca dio asc. Dis. 2022,32, 863–877. [C ossRe ] [PubMed]
60.
Ge e s, D.; Kuga hasan, S.; Denson, L.A.; Vázquez-Baeza, Y.; Van T eu en, W.; Ren, B.; Schwage , E.; Knigh s, D.; Song, S.J.;
Yassou , M.; e al. The T ea men -Nai e Mic obiome in New-Onse C ohn’s Disease. Cell Hos Mic obe
2014
,15, 382–392. [C ossRe ]
61.
Khan, I.; Ullah, N.; Zha, L.; Bai, Y.; Khan, A.; Zhao, T.; Che, T.; Zhang, C. Al e a ion o Gu Mic obio a in In lamma o y Bowel
Disease (IBD): Cause o Consequence? IBD T ea men Ta ge ing he Gu Mic obiome. Pa hogens 2019,8, 126. [C ossRe ]
62.
Loy, A.; P ann, C.; S einbe ge , M.; Hanson, B.; He p, S.; B ugi oux, S.; Gomes-Ne o, J.C.; Boekscho en, M.V.; Schwab, C.; U ich, T.; e al.
Li es yle and Ho izon al Gene T ans e -Media ed E olu ion o Mucispi illum schaedle i, a Co e Membe o he Mu ine Gu
Mic obio a. mSys ems 2017,2, e00171-16. [C ossRe ] [PubMed]
63.
Ge achew, B.; Aubee, J.I.; Scho en eld, R.S.; Csoka, A.B.; Thompson, K.M.; Tizabi, Y. Ke amine in e ac ions wi h gu -mic obio a
in a s: Rele ance o i s an idep essan and an i-in lamma o y p ope ies. BMC Mic obiol. 2018,18, 222. [C ossRe ]
64.
Miquel, S.; Ma ín, R.; B idonneau, C.; Robe , V.; Sokol, H.; Be mudez-Huma an, L.G.; Thomas, M.; Langella, P. Ecology
and me abolism o he bene icial in es inal commensal bac e iumFaecalibac e ium p ausni zii. Gu Mic obes
2014
,5, 146–151.
[C ossRe ] [PubMed]
65.
Meehan, C.; Beiko, R.G. A Phylogenomic View o Ecological Specializa ion in he Lachnospi aceae, a Family o Diges i e
T ac -Associa ed Bac e ia. Genome Biol. E ol. 2014,6, 703–713. [C ossRe ] [PubMed]
66.
Säemann, M.D.; Böhmig, G.A.; Ös e eiche , C.H.; Bu sche , H.; Pa olini, O.; Diakos, C.; S öckl, J.; Hö l, W.H.; Zlabinge , G.J.
An i-in lamma o y e ec s o sodium bu y a e on human monocy es: Po en inhibi ion o IL-12 and up- egula ion o IL-10
p oduc ion. FASEB J. 2000,14, 2380–2382. [C ossRe ] [PubMed]
67.
Ke n, T.; Blond, M.B.; Hansen, T.H.; Rosenkilde, M.; Quis , J.S.; G am, A.S.; Eks øm, C.T.; Hansen, T.; S allknech , B. S uc u ed
exe cise al e s he gu mic obio a in humans wi h o e weigh and obesi y—A andomized con olled ial. In . J. Obes.
2019
,44,
125–135. [C ossRe ] [PubMed]
68.
Mo iani, K.K.; Collado, M.C.; Eskelinen, J.J.; Vi anen, K.A.; Löy yniemi, E.; Salminen, S.; Nuu ila, P.; Kalliokoski, K.K.;
Hannukainen, J.C. Exe cise aining modula es gu mic obio a p o ile and imp o es endo oxemia. Med. Sci. Spo s Exe c.
2020
,52,
94–104. [C ossRe ]
69.
McKee, L.S.; La Rosa, S.L.; Wes e eng, B.; Eijsink, V.G.; Pope, P.B.; La sb ink, J. Polysaccha ide deg ada ion by he Bac e oide es:
Mechanisms and nomencla u e. En i on. Mic obiol. Rep. 2021,13, 559–581. [C ossRe ] [PubMed]
70.
Flin , H.J.; Sco , K.P.; Duncan, S.H.; Louis, P.; Fo ano, E. Mic obial deg ada ion o complex ca bohyd a es in he gu . Gu Mic obes
2012,3, 289–306. [C ossRe ] [PubMed]
71.
Da ila, A.-M.; Blachie , F.; Go eland, M.; And iamihaja, M.; Bene i, P.-H.; Sanz, Y.; Tomé, D. In es inal luminal ni ogen
me abolism: Role o he gu mic obio a and consequences o he hos . Pha macol. Res. 2013,68, 95–107. [C ossRe ] [PubMed]
72.
Newga d, C.B.; An, J.; Bain, J.R.; Muehlbaue , M.J.; S e ens, R.D.; Lien, L.F.; Haqq, A.M.; Shah, S.H.; A lo o, M.; Slen z, C.A.; e al.
A B anched-Chain Amino Acid-Rela ed Me abolic Signa u e ha Di e en ia es Obese and Lean Humans and Con ibu es o
Insulin Resis ance. Cell Me ab. 2009,9, 311–326. [C ossRe ] [PubMed]
73.
Newga d, C.B. In e play be ween Lipids and B anched-Chain Amino Acids in De elopmen o Insulin Resis ance. Cell Me ab.
2012,15, 606–614. [C ossRe ]

In . J. En i on. Res. Public Heal h 2022,19, 9518 17 o 17
74.
Yoon, M.-S. The Eme ging Role o B anched-Chain Amino Acids in Insulin Resis ance and Me abolism. Nu ien s
2016
,8, 405.
[C ossRe ] [PubMed]
75.
Shou, J.; Chen, P.-J.; Xiao, W.-H. The E ec s o BCAAs on Insulin Resis ance in A hle es. J. Nu . Sci. Vi aminol.
2019
,65, 383–389.
[C ossRe ]
76.
Su yani, D.; Al aqih, M.S.; Gunadi, J.W.; Syl iana, N.; Goenawan, H.; Megan a a, I.; Lesmana, R. Type, In ensi y, and Du a ion o
Exe cise as Regula o o Gu Mic obiome P o ile. Cu . Spo s Med. Rep. 2022,21, 84–91. [C ossRe ] [PubMed]
77.
Dupui , M.; Rance, M.; Mo el, C.; Bouillon, P.; Bosca o, A.; Ma in, V.; Vazeille, E.; Ba nich, N.; Chassaing, B.; Boisseau, N. E ec o
Concu en T aining on Body Composi ion and Gu Mic obio a in Pos menopausal Women wi h O e weigh o Obesi y. Med. Sci.
Spo s Exe c. 2021,54, 517–529. [C ossRe ] [PubMed]
78.
Munukka, E.; Ah iainen, J.P.; Puigbó, P.; Jalkanen, S.; Pahkala, K.; Keski alo, A.; Kujala, U.M.; Pie ilä, S.; Hollmén, M.; Elo, L.; e al.
Six-Week Endu ance Exe cise Al e s Gu Me agenome Tha Is no Re lec ed in Sys emic Me abolism in O e -weigh Women.
F on . Mic obiol. 2018,9, 2323. [C ossRe ] [PubMed]
79.
Wang, J.; Zhang, Q.; Xia, J.; Sun, H. Mode a e T eadmill Exe cise Modula es Gu Mic obio a and Imp o es In es inal Ba ie in
High-Fa -Die -Induced Obese Mice ia he AMPK/CDX2 Signaling Pa hway. Diabe es Me ab. Synd . Obes.
2022
,15, 209–223.
[C ossRe ] [PubMed]
80.
Es aki, M.; Pi he , J.; Baumeis e , P.; Li le, J.P.; Gill, S.K.; Ghosh, S.; Ahmadi-Vand, Z.; Ma sden, K.R.; Gibson, D.L. Ca dio espi a-
o y i ness as a p edic o o in es inal mic obial di e si y and dis inc me agenomic unc ions. Mic obiome
2016
,4, 42. [C ossRe ]
[PubMed]
81.
Guinane, C.M.; Co e , P.D. Role o he gu mic obio a in heal h and ch onic gas oin es inal disease: Unde s anding a hidden
me abolic o gan. The . Ad . Gas oen e ol. 2013,6, 295–308. [C ossRe ]
82.
Huang, W.-C.; Chen, Y.-H.; Chuang, H.-L.; Chiu, C.-C. In es iga ion o he E ec s o Mic obio a on Exe cise Physiological
Adap ion, Pe o mance, and Ene gy U iliza ion Using a Gno obio ic Animal Model. F on . Mic obiol. 2019,10, 1906. [C ossRe ]
83.
Sun, S.; Lei, O.K.; Nie, J.; Shi, Q.; Xu, Y.; Kong, Z. E ec s o Low-Ca bohyd a e Die and Exe cise T aining on Gu Mic obio a.
F on . Nu . 2022,9, 884550. [C ossRe ] [PubMed]