nu ien s
Re iew
Impac o Exe cise on Gu Mic obio a in Obesi y
Je ónimo A agón-Vela 1,2,* , Pa icio Solis-U a 3,4 , F ancisco Ja ie Ruiz-Ojeda 2,5,6,7,
Ana Isabel Ál a ez-Me cado 2,5,6 , Jo ge Oli a es-A ancibia 8,9 and Julio Plaza-Diaz 5,6,10,*


Ci a ion: A agón-Vela, J.; Solis-U a,
P.; Ruiz-Ojeda, F.J.; Ál a ez-Me cado,
A.I.; Oli a es-A ancibia, J.;
Plaza-Diaz, J. Impac o Exe cise on
Gu Mic obio a in Obesi y. Nu ien s
2021,13, 3999. h ps://doi.o g/
10.3390/nu13113999
Academic Edi o s: Na halie Boisseau
and Nicolas Ba nich
Recei ed: 15 Oc obe 2021
Accep ed: 8 No embe 2021
Published: 10 No embe 2021
Publishe ’s No e: MDPI s ays neu al
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1Depa men o Physiology, School o Pha macy, Uni e si y o G anada, Campus de Ca uja s/n,
18071 G anada, Spain
2Ins i u e o Nu i ion and Food Technology “JoséMa aix”, Cen e o Biomedical Resea ch, Uni e si y o
G anada, A da. del Conocimien o s/n, 18016 G anada, Spain; [email p o ec ed] (F.J.R.-O.);
al a ezme cado@ug .es (A.I.Á.-M.)
3PROFITH “PROmo ing FITness and Heal h h ough Physical Ac i i y” Resea ch G oup, Depa men o
Physical Educa ion and Spo s, Facul y o Spo s Science, Uni e si y o G anada, 18071 G anada, Spain;
[email p o ec ed]
4Facul y o Educa ion and Social Sciences, Uni e sidad And es Bello, Viña del Ma 2531015, Chile
5Depa men o Biochemis y and Molecula Biology II, School o Pha macy, Uni e si y o G anada,
18071 G anada, Spain
6Ins 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
7
RG Adipocy es and Me abolism, Ins i u e o Diabe es and Obesi y, Helmhol z Diabe es Cen e a Helmhol z
Cen e Munich, Neuhe be g, 85764 Munich, Ge many
8G upo AFySE, In es igación en Ac i idad Física y Salud Escola , Escuela de Pedagogía en Educación Física,
Facul ad de Educación, Uni e sidad de las Amé icas, San iago 8370035, Chile; jo ge.oli a [email p o ec ed]
9IRyS Resea ch G oup, School o Physical Educa ion, Pon i icia Uni e sidad Ca ólica de Valpa aíso,
Valpa aíso 2374631, Chile
10 Child en’s Hospi al o Eas e n On a io Resea ch Ins i u e, O awa, ON K1H 8L1, Canada
*Co espondence: je oa @ug .es (J.A.-V.); j plaza@ug .es (J.P.-D.); Tel.: +34-958220319 (J.A.-V.);
+34-958241599 (J.P.-D.)
Abs ac :
Physical ac i i y, exe cise, o physical i ness a e being s udied as help ul nonpha maco-
logical he apies o educe signaling pa hways ela ed o in lamma ion. S udies desc ibing changes
in in es inal mic obio a ha e s a ed ha physical ac i i y could inc ease he mic obial a iance
and enhance he a io o Fi micu es/Bac e oide es, and bo h ac ions could neu alize he obesi y
p og ession and diminish body weigh . The aim o his e iew is o p o ide an o e iew o he
li e a u e desc ibing he ela ionship be ween physical ac i i y p o iles and gu mic obio a and in
obesi y and some associa ed como bidi ies. P omo ing physical ac i i y could suppo as a ea men
o main ain he gu mic obio a composi ion o o es o e he balance owa d an imp o emen o
dysbiosis in obesi y; howe e , hese mechanisms need o be s udied in mo e de ail. The oppo uni y
o con ol he mic obio a by physical ac i i y o imp o e heal h esul s and dec ease obesi y and
ela ed como bidi ies is e y a ac i e. Ne e heless, se e al incomple ely answe ed ques ions need
o be add essed be o e his s a egy can be implemen ed.
Keywo ds:
gu mic obio a; physical ac i i y; heal h; obesi y; child en; humans; non-communicable
diseases
1. In oduc ion
A posi i e ene gy balance causes excessi e lipid accumula ion in adipose issue ha
in luences he a ec ed indi idual in ega ds o o he diseases such as insulin esis ance, ca -
dio ascula diseases ha can culmina e in ce ain ypes o cance s and ype 2 diabe es [
1
].
Indeed, isce al a a he han o al a is he main d i e o insulin esis ance and o he
como bidi ies such as dyslipidemia and ch onic low-g ade in lamma ion s a us in indi id-
uals [
2
]. A he cellula le el, adipocy e hype ophy esul s in comp omised blood supply
Nu ien s 2021,13, 3999. h ps://doi.o g/10.3390/nu13113999 h ps://www.mdpi.com/jou nal/nu ien s
Nu ien s 2021,13, 3999 2 o 15
o adipose issue, highe ib osis, hypoxia, sys emic and local in lamma ion, and insulin
esis ance in he adipocy es [3,4].
Al hough scien is s con inue making subs an ial p og ess in unde s anding adipose
issue unc ion, p e en ion, and ea men o obesi y, he pandemic con inues o sp ead and
is one o he main heal h complica ions in indus ialized and de eloping coun ies [
5
]. In
Eu ope, he o e weigh p e alence is expec ed o be nea 50%, and he obesi y p e alence
o be app oxima ely 24% o he popula ion [
6
], inc easing om 11% in 2000 o 24% in 2018,
on ypical h ough Eu opean membe s a es [
6
,
7
]. I is no ewo hy ha high-calo ie die s
and he absence o physical ac i i y, which is s ongly a ec ed by a a ie y o ac o s such
as li es yle and socioeconomic s a us, play a pa in he ad ance o me abolic diseases [8].
Despi e he mul iple ac o s ha in e ac in he p og ess o obesi y, he gu mic obio a
seems o be a c i ical ole as a bodyweigh egula o [
9
]. In ac , Liu e al. ha e epo ed
ele a ed body mass index (BMI) and adiposi y, dyslipidemia, insulin esis ance, and a mo e
ma ked in lamma o y s a us in indi iduals who ha e also exhibi ed signi ican ly lesse
di e si y in gu bac e ia [
10
]. Nume ous mechanisms ha e been sugges ed o elucida e he
po en ial ole o gu mic obio a in obesi y p og ess.
The e m mic obio a includes he ull collec ion o mic obes (bac e ia, ungi, and
i uses, among o he s) ha na u ally subsis wi hin a pa icula biological niche, a ound
500–1000 species, and hei impac on human heal h [
11
]. Se e al endogenous and exoge-
nous ac o s a e in ol ed in he gu mic obio a such as he deli e y me hod o a neona e,
hos immune esponse, die , an ibio ics, hos gene ic ea u es, o he d ugs, in ec ions,
diu nal hy hm, and en i onmen al mic obial exposu es [12,13].
Wi h ega ds o obesi y, a high- a die causes sys emic insulin esis ance and me abolic
dys unc ion in mice, which d i es a unc ional and s uc u al dysbiosis o he gu mic o-
bio a, de ined as “a educ ion in mic obial di e si y and a combina ion o he loss o
bene icial bac e ia such as Bac e oides s ains and bu y a e-p oducing bac e ia” [
12
,
14
,
15
],
inc easing Lac ococcus and lowe ing Tu icibac e , which con e an enhanced in lamma o y
esponse [
16
]. The sys emic in lamma ion in obesi y is ela ed o augmen ed in es inal pe -
meabili y, which is linked wi h “leaky gu ” and gu dysbiosis, which is a new objec i e o
he apy and disease p e en ion [
17
]. Indeed, dis u bances o gu mic obio a composi ion
may upsu ge he leakage o he mucosa, inc easing he seepage o bac e ia and bac e ia
componen s such as lipopolysaccha ide (LPS) ac oss he in es inal mucosa [
18
]. In addi ion,
i is well-known ha obesi y causes a educ ion in he a io o Bac e oide es/Fi micu es and
g ea e le els o P e o ella [
19
]. Thus, main aining and es o ing a heal hy gu mic obio a
can help p e en he ini ial s a and p og ess o me abolic diseases, including obesi y.
Mic obial dysbiosis could be de e mined using bioin o ma ic analysis wi h ecological
a iables, such as di e si y (alpha o be a), species ichness [
20
], mic obial abundances
such as Bac e oide es/Fi micu es a io [
21
], and clinical measu es such as o ganic acid
es [22] and hyd ogen b ea h es [23].
Nume ous me aboli es a e c ea ed by gu mic obio a om he die a y me abolism
such as sho -chain a y acids (SCFAs), ime hylamine, and ime hylamine N-oxide,
among o he s, which a e linked o me abolic diso de s pa hogenesis [
24
]. In his con ex ,
new ea men s (including p e and p obio ics) such as ecal mic obio a ansplan a ion [
25
],
pe sonalized nu i ion, die a y educa ion, and physical ac i i y [
26
] may help o ees ablish
and/o p ese e he composi ion o gu mic obio a, changing he b ain–gu axis and
dec easing pa hology isk [
27
]. In pa icula , physical exe cise induces changes in mic obial
di e si y, ca dio espi a o y i ness, and insulin esis ance among o he s [28].
The composi ion o gu mic obio a is di ec ly linked o sys emic me abolic homeos asis
and adiposi y, which in luences he p og ess o obesi y. Though se e al mechanisms be-
ween mic obial di e si y and me abolic heal h ha e been desc ibed, he causal ela ionship
is no comple ely unde s ood [29–31].
Exe cise is ecognized o s abilize he p og ession o obesi y and modi y he gu
mic obio a composi ion by inc easing he mic obial di e si y [
32
,
33
], imp o ing he Fi -
micu es/Bac e oide es a io ha could po en ially con ibu e o dec easing body weigh ,
Nu ien s 2021,13, 3999 3 o 15
obesi y-associa ed pa hologies, and gas oin es inal diso de s [
32
]. In addi ion, exe cise
is conside ed an e icien non-pha macological he apy by dec easing in lamma o y sig-
naling pa hways [
34
]. O e all, p omo ing exe cise could help as a ea men o main ain
he composi ion o gu mic obio a o o es o e he balance owa d an imp o emen o
dysbiosis in obesi y; howe e , hese mechanisms need o be s udied in mo e de ail. In he
p esen wo k, we e iew he li e a u e desc ibing he associa ion be ween exe cise and gu
mic obio a in obesi y and i s associa ed como bidi ies.
2. Physical Ac i i y, Exe cise, and Physical Fi ness and Thei Rela ionship wi h
Obesi y and Heal h Main enance
Physical ac i i y, exe cise, and physical i ness a e e ms ha de ine dis inc concep s.
Physical ac i i y is well desc ibed as e e y physical mo emen using skele al muscles
ha p oduce an ene gy expendi u e in daily li e ha can be ca ego ized in o occupa ional,
household, spo s, condi ioning, o o he ac i i ies [
35
]. Exe cise is a subsec ion o physical
ac i i y ha is s uc u ed, p emedi a ed, and cyclic and has as a inal o an in e media e
objec i e he p og ess o physical i ness main enance, ha is, a g oup o aspec s ha a e
bo h skills- o heal h- ela ed [36].
The mos in-dep h and s aigh o wa d consequence associa ed wi h exe cise bene i s
is weigh loss, wi h he p obable o mi iga e o e e se he cou se o obesi y and co-
mo bidi ies e en wi h no die a y in e en ion [
37
–
39
]. Physical ac i i y impo ance o
weigh loss e alua ed by BMI is deba ed, bu i is well es ablished he e ec o exe cise on
adiposi y and se e al ch onic diseases. Ins ead, he e is obus e idence desc ibing how
physical ac i i y le els and exe cise in e en ion a e impo an o a oid weigh egain a e
weigh loss [40–45].
Acco ding o an h opome y, he e a e o he measu es ins ead BMI ha migh be
ela ed o he gu mic obio a, wais ci cum e ence, hip ci cum e ence, and wais - o-hip
a io, which ha e become impo an indica o s o adiposi y, disease isk, and mo ali y
isk [
46
,
47
]. Recen ly, Osbo ne e al. ha e epo ed he associa ions be ween some o he
a o emen ioned a iables wi h he composi ion o gu mic obio a. Pa icipan s wi h high
alues o BMI, mid-uppe a m ci cum e ence, wais ci cum e ence, and wais - o-hip a io
we e ela ed o a diminished alpha di e si y. Oscillospi a and he amily S24-7 ela i e
abundances we e in e sely associa ed wi h an h opome ic measu es. BMI and wais and
hip ci cum e ences we e ela ed posi i ely o Acidaminococcus, especially mo e in women
han in men [47].
One o he p oposed mechanisms is ha physical ac i i y aises ene gy expendi u e
ac i a ing lipolysis, so he a mass is diminished i he ene gy consumed is no eimbu sed
o wi h a ise in calo ic in ake, main aining a nega i e ene gy balance [
48
]. On he con a y,
physical inac i i y in con empo a y obesogenic ci cums ances o igina es maladap a ion,
cha ac e ized by a posi i e ene gy balance, causing long-las ing disease and becoming a
main public heal h p oblem [
49
]. Ne e heless, egula physical ac i i y has a deep exp es-
sion e ec on ou genome [
50
], which has been p e e ed o enhancing ae obic me abolism
o main ain ene gy in a si ua ion o ood insu iciency [
51
,
52
], occasioning nume ous a o -
able adap a ions and educed isk o ch onic diseases [
53
]. The iden i ica ion o adap a ions
o exe cise is ad ancing ou knowledge o he pa hophysiology o long-las ing diseases
and a ying old iews, which migh bene i new he apeu ic app oaches and a ge s [53].
3. Physical Ac i i y and Gu Mic obio a in Obesi y
Li es yle changes a e s ill he mos widely used and ecommended s a egies o achie e
weigh educ ion in obesi y, pa icula ly using di e en die a y s a egies and p omo ing
physical ac i i y and exe cise [
54
]. Recen au ho s conclude ha he e seems o be an
in ima e associa ion be ween he gu mic obio a and li es yle p oposing ha an ac i e
li es yle may imp o e he quali y o he mic obio a [
55
]. In his sense, obesi y is ela ed o
mino di e si y and ichness o he in es inal mic obio a, wi h a lowe a io o Bac e oide es-
o-Fi micu es [
29
]. Indeed, exe cise aining imp o es obesi y s a us by inc easing insulin
sensi i i y, educing sys emic in lamma ion, and imp o ing VO
2max
[
56
]. Thus, acco ding
Nu ien s 2021,13, 3999 4 o 15
o da a om ecen epidemiological, physiological, and omics-based s udies, comple ed
h ough s udies in animals and cells s udies, i seems plausible ha mic obial communi ies
migh be di ec ly o indi ec ly in luenced, among o he en i onmen al ac o s, by physical
ac i i y o exe cise [57,58].
Main aining o es o ing mic obial di e si y is essen ial o a oid pe u bed in es inal
homeos asis, which is ela ed o dysbiosis. The excessi e p oduc ion o SCFA, due o
e men a ion o non-diges ible ood polysaccha ides by in es inal bac e ia, may induce
lipogenesis in he li e and accumula ion o iglyce ides in hos adipocy es [
5
]. Indeed,
hese SCFAs may also be implica ed in al e a ions associa ed wi h insulin esis ance, gi en
ha one o he objec i es o hese SCFA induced signals is glucose homeos asis [
59
].
This is possible due o glucagon-like pep ide 1 (GLP-1), a ecognized media o ela ed o
glucose homeos asis. In gene al e ms, GLP-1 is p oduced in he in es ine and has a c i ical
p o agonis in adjus ing he plasma glucose concen a ion [
59
]. In e es ingly, a ecen s udy
e eals ha ec al adminis a ion o SCFAs inc eases he GLP-1 sec e ion, con i ming a
close associa ion be ween GLP-1 and SCFAs [
60
]. The e o e, a ecal bac e ia educ ion may
p oduce glucose in ole ance h ough a educ ion in he sec e ion o GLP-1 [
61
]. Ano he
mechanism sugges ed cla i ying he connec ion be ween obesi y and he gu mic obio a is
he ole o he ac i a ion o adenosine monophospha e kinase (AMPK). One o he main
unc ions o AMPK is he oxida ion o a y acids [
62
]. The e o e, i s inhibi ion could cause
an inc eased a accumula ion [63].
4. Physical Ac i i y and Mic obio a: Some Unde lying Mechanisms
Physical ac i i y can s imula e a ia ions in he gu mic obio a by nume ous mecha-
nisms such as myokines elease, inc eased in es inal ansi , o he sec e ion o neu o ans-
mi e s and ho mones [
64
]. Howe e , he in e -indi idual a ia ion and gu mic obio a
plas ici y ha e hampe ed e o s o iden i y a “heal hy” in es inal mic obio a. Indeed, in ad-
di ion o physical ac i i y, many ac o s lead o ins abili y o he gu mic obio a, such as die ,
sleep pa e n, an ibio ic exposu e, and a ious como bidi ies [
65
]. Impo an ly, a heal hy
mic obio a is in ol ed in he immune sys em de elopmen , wi h an an i-in lamma o y
ole h ough educing his one deace ylases in egula o y T cells by G p o ein-coupled
ecep o s [65].
Recen s udies by Cas ellanos e al. epo ed ha ac i e indi iduals who mee he ec-
ommenda ions o physical ac i i y and die om he Wo ld Heal h O ganiza ion (WHO)
exhibi di e en ela i e abundances o h ee species o he Bac e oides genus: B. uni o mis,
B. o a us, and an unclassi ied species [
66
]. Indeed, changes in he composi ion o he
mic obio a ollowing an ac i e li es yle a e associa ed wi h inc eases in SCFA, such as
n-bu y a e, which can modula e hos ene gy balance and lead o inc eased nu ien a ail-
abili y [
67
]. On he o he hand, a seden a y li es yle is ela ed o a signi ican ly diminished
di e si y and a less dense mic obial ne wo k s uc u e [
66
]. In his con ex , gu mic obio a
di e si y has de eloped as a candida e indica o o o e all hos heal h, he gu mic obio a
ne wo k o ac i e people being mo e obus han ha o seden a y people [
64
]. Thus, ac i e
people, who display a mo e di e se mic obial communi y, appea o be mo e s able, esis
pa hogenic in asions, exhibi g ea e esilience, and show unc ional edundancy leading
o mo e e icien esou ce u iliza ion han seden a y indi iduals [
68
]. Fu he mo e, his
phenomenon o inc eased bac e ial di e si y could help o es o e and a oid dysbiosis,
especially in se e e si ua ions such as he use o an ibio ics, which his ea men pe se
d i es a dec ease o some bac e ial species [
66
]. In conco dance wi h hese esul s, B essa
e al. showed ha physical ac i i y execu ed a sho doses bu con inuously may ise
he heal h-p omo ing bac e ia abundance (Bi idobac e ium spp., Akke mansia muciniphila,
Rosebu ia hominis, and Faecalibac e ium p ausni zii) in he gu mic obio a [
55
]. Howe e , a
seden a y li es yle is in e sely associa ed wi h in es inal mic obio a ichness [
55
]. Ke n e al.
demons a ed ha exe cise inc eases alpha di e si y and dis u bs he gene al mic obio a
composi ion in indi iduals wi h o e weigh and obesi y a e 6 mon hs o in e en ion in a
andomized clinical ial (RCT) [
69
]. Simila ly, ano he ial e ealed ha bo h mode a e-
Nu ien s 2021,13, 3999 5 o 15
in ensi y exe cise and esis ance aining o 8 weeks igge shi s in mic obial di e si y, in
pa icula , alpha bac e ia [
70
]. Mahdieh e al. epo ed an imp o emen o Bi idobac e ium
coun s in 18 women wi h obesi y who we e aining ae obic exe cise (3 sessions pe week,
las ing 30–45 min) o 10 weeks [
71
]. In addi ion, hey showed how exe cise dec eases in-
es inal in lamma ion and modi ies gu mic obio a p o ile in insulin- esis an subjec s [
72
].
The e o e, physical ac i i y is sugges ed as a use ul non-pha macologic ins umen o
coun e ac pa hological al e a ions o he gu mic obio a in o de o p e en me abolic
dis u bances, especially in obesi y. In addi ion, a seden a y li es yle has ma e ialized as a
new isk a iable o heal h, which is ela ed o a high incidence o ch onic diseases such
as cance ca dio ascula diseases and ype 2 diabe es [
64
,
67
], wi h obesi y being he main
con ibu o o he de elopmen o hese pa hologies [5].
Some p oposal mechanisms o he in es inal mic obio a and obesi y a e ela ed o
p ima y bile acids sa ely con e ed by gu mic obio a o seconda y bile acids ha pe o m
h oughou he TGR5 ecep o o s imula e GLP-1 elease imp o ing he mogenesis in
adipose issue [
57
,
73
] and also by he nuclea a nesoid X ecep o ela ed o ca bohyd a e
me abolism [74].
The die a y ibe e men a ion by mic obes, belonging especially o Fi micu es and
Bac e oide es, c ea es SCFAs (p opiona e, bu y a e, and ace a e) ha impac he hos
me abolism in se e al ways by pe o ming on G p o ein-coupled ecep o s exp essed by
en e oendoc ine cells [
75
,
76
]. SCFAs could s imula e GLP-1 and pep ide YY libe a ion
a ec ing he b ain and panc eas, and ace a e may imp o e a s o age h ough he ac ion o
gh elin sec e ion [76,77].
LPS, compounds ound in G am-nega i e bac e ia, a e ela ed o in lamma ion p o-
cesses [
77
]. In addi ion, succina e, a mic obial-de i ed, could ha e p o-in lamma o y
ac ions on LPS-de i ed mac ophages and migh he e o e cause in lamma ion and insulin
esis ance in adipose issue [
78
]. O he s udies suppo ha succina e could ac i a e he
uncoupling p o ein 1 exp ession ha a ec s he adipose issue he mogenesis [79,80]
Gu bac e ial-de i ed b anched-chain amino acids ela ed, in cases o high a in ake,
o insulin esis ance in bo h oden s and humans [
57
,
81
]. Sec e ed p o eins h ough gu
bac e ia also egula e endoc ine o pa ac ine ac ion (e.g., G p o ein-coupled ecep o
119) [82].
Finally, physical ac i i y could be a en a i e ea men o p oduce di e en ac ions in
speci ic le els, changing he mic obio a composi ion and ac i a ing o e speci ic p o eins,
such as uncoupled p o ein 1, o s imula ing he libe a ion o SCFAs.
5. Obesi y, Die In e en ions, Physical Ac i i y/Exe cise, and Thei Impac on Gu
Mic obio a
Al hough scien is s con inue o make subs an ial p og ess in imp o ing li es yles in
o de o dec ease he epidemic o obesi y and i s ela ed o como bidi ies, o cou se, lack o
physical ac i i y (s ongly a ec ed by a a ie y o ac o s, p ima ily socioeconomic and
li es yle s a us) and high-calo ie die s ac as an impo an pa in he p og ess o me abolic
diseases. The i s ecommended ea men o obesi y is a low-calo ie die and egula
physical ac i i y. Howe e , hese li es yle in e en ions ha e low o e all compliance and
limi ed e ec i eness in people wi h obesi y. In adul s, Mu alidha an e al. [
31
] e ealed ha
ene gy es ic ion and Medi e anean die wi h physical ac i i y, and beha io al suppo
could p o oke a educ ion in nume ous Fi micu es membe s, especially belonging o
Lachnospi aceae a e 1-yea o in e en ion in indi iduals wi h obesi y and o e weigh .
In addi ion, hey obse ed a selec i e ise in some SCFA p oduce s [
31
]. This ype o
in e en ion may ha e a bene icial e ec on ca dio ascula diseases, po en ially modula ed
by gu mic obio a [
31
]. Fu he mo e, Allen e al. showed ha exe cise-induced modula ion
o in es inal mic obio a and SCFAs we e ela ed o changes in VO
2max
a e 6 weeks o
ae obic exe cise in indi iduals wi h obesi y [
56
]. In addi ion, hey obse ed ha he
e u n o he seden a y s a e was in e sely associa ed wi h he changes ha happened in
esponse o exe cise aining [
56
]. O e all, hese indings con i m ha physical ac i i y and
die a y con ol con ibu e signi ican ly o imp o ing he composi ion o he gu mic obio a.

Nu ien s 2021,13, 3999 6 o 15
Mo eo e , i appea s ha exe cise on ecal SCFAs le els is posi i ely co ela ed wi h body
composi ion [
83
]. One o he possible mechanisms ha could explain his heo y could
be ha SCFAs may imp o e skele al muscle insulin sensi i i y and egula e sa ie y [
84
],
wi h an impac on body composi ion. In addi ion, SCFAs a e also ene gy subs a es
o se e al issue ypes, such as adipose issue, colon, and muscle [
56
], sugges ing ha
SCFAs may imp o e ene gy in ake om he die , ul ima ely leading o inc eased issue
de elopmen , including skele al muscle [
67
]. Ano he mechanism ha could explain he
bene i s o physical ac i i y on he in es inal mic obio a is he shi in gu pH du ing
physical ac i i y [
83
]. These changes migh p oduce an en i onmen al se ing allowing
o iche communi y di e si y. Mo eo e , esis ance aining may cause changes in he
gas oin es inal ac , as low issue hypoxia and blood low, d i ing o inc eased abso p ion
capaci y and ansi [85].
5.1. Child en and Adolescen Popula ion
In e es ing a ge popula ion s udies a e child en and adolescen s wi h obesi y. In
his line, a ecen sys ema ic e iew e alua ed he composi ion o gu mic obio a ela ed o
adiposi y in child en and adolescen s, concluding ha he e is an absence o consensus o
he composi ion o in es inal mic obio a associa ions wi h adiposi y. Mo eo e , he heal hy
gu mic obio a a e ela ed o a die ich in ui s and ege ables wi h mode a e consump ion
o animal a and p o ein [
86
]. O no e, e en he ma e nal gu mic obio a al e a ions
du ing impo an phases o emb yonic, e al, and ea ly pos na al de elopmen could ha e
consequences on he gu mic obio a o sp ing, wi h li elong e ec s o suscep ibili y o
disease [
87
]. A ecen s udy indica ed ha he di e si y and abundance o gu mic obio a in
child en wi h obesi y we e signi ican ly mino han hose in no mal-weigh child en [88].
An exe cise p og am combined wi h die a y es ic ions may imp o e gu mic obio a
heal h in child en wi h obesi y. Ne e heless, he mos e ec i e aining p og am is no
s ill well es ablished, hough i seems ha he combined aining p og am o esis ance and
ae obic exe cise could be able o dec ease body a and inc ease gu di e si y [
34
,
54
]. Huang
e al. epo ed ha a six-week exe cise aining (ae obic and esis ance exe cises) wi h
die a y es ic ion no only dec eased bodyweigh bu also inc eased cen al hemodynamic
measu es (pe iphe al a e iola esis ance and mic o ascula co ona y pe usion) ha we e
ela ed o modi ying gu mic obio a in adolescen s wi h obesi y [89]. In addi ion, a ecen
s udy has epo ed ha six weeks o exe cise and he die a y p og am a e use ul ools in
o de o inc ease au onomic unc ion and cen al hemodynamics wi h educed a e ial
s i ness in adolescen s wi h obesi y [
90
]. Mo eo e , Cho e al., wi h a weigh educ ion
p og am ha in ol ed die a y al e a ion, augmen ed beha io al modi ica ion and physical
ac i i y du ing 2 mon hs in child en wi h obesi y, obse ed signi ican modi ica ions in he
gu mic obio a composi ion, and expec ed unc ional p o iles o he gu mic obio a and
ichness wi h weigh loss a e li es yle changes [
91
]. On he o he hand, Qui oga e al.,
wi hou nu i ional in e en ion, show h ough ae obic and esis ance combined aining
du ing 12 weeks in hi y-nine child en wi h obesi y ha he exis ence o a de imen al
mic obio a p o ile in obesi y is al e ed by exe cise in e en ion, emphasizing he alue o
exe cise ou ine as an e ec i e non-pha macological he apy in ea ly obesi y [34]. Finally,
in child en wi h o e weigh and obesi y, i is desc ibed ha oligo uc ose-en iched inulin
p ebio ics modi y he gu mic obio a composi ion and mode a ely dec ease in lamma o y
bioma ke s, adiposi y, and body weigh [92].
5.2. Physical Ac i i y, Die , Mic obio a, and T ea men
Physical ac i i y signi ican ly dec eases he Gammap o eobac e ia and P o eobac e ia.
Mo eo e , i ended o ise Dialis e ,Blau ia, and Rosebu ia, c ea ing a mic obio a p o ile
simila o ha o heal hy child en. T aining p o ocol signi ican ly ep essed he igge ing o
he obesi y-associa ed NLRP3 signaling pa hway [
34
]. Howe e , he e a e limi ed indings
o he gu mic obio a composi ion in obese child en, deno ing ha addi ional analysis
es ablished on he unc ion o he in es inal mic obio a in childhood obesi y is necessa y.
Nu ien s 2021,13, 3999 7 o 15
A sys ema ic e iew o he ou comes o nine c oss-sec ional s udies and six in e en-
ions epo ing he ou comes o die a y a on in es inal mic obio a in humans [
93
] showed
ha die s wi h excessi e sa u a ed o monounsa u a ed a s ha m ully p edisposed he gu
mic obio a while die s high in polyunsa u a ed a seemed o be neu al wi h espec o
he gu mic obio a. Simila ly, high-polysaccha ide die in e en ions ha e caused di e en
gu mic obio a connec ed wi h se um, inc eased ecal, o u ine concen a ions o SCFAs,
imp o emen s o cy okine and me abolome p o iles, and weigh loss [
94
–
97
]. Likewise,
in e en ions wi h augmen ed physical ac i i y ha e exhibi ed adap i e and ansmissible
a ia ions o he in es inal mic obio a connec ed wi h an augmen ed capaci y o he b eak-
down o b anched-chain amino acids and lac a e, an augmen ed po en ial o syn hesis o
SCFAs, and imp o emen s in insulin sensi i i y and ca dio espi a o y i ness.
Lac obacillus,Bi idobac e ium, and Saccha omyces spp. a e gene ally ecognized as sa e
(GRAS) p obio ics [
98
–
100
], and in he pas yea s, new membe s ha e been included
such as F. p ausni zii [
101
], A. muciniphila [
102
], and nume ous Clos idia spp. [
103
]. New
da a ha e epo ed ha i is possible ha some p obio ics, A. muciniphila s ains, do no
e en equi e colonizing he in es ine o ob ain help ul me abolic e ec s in he hos ela ed
o heal h [
104
,
105
]. RCTs assessmen o p ebio ics (non-diges ible polysaccha ides) has
epo ed ha inulin- ype uc ans ans o med he gu mic obio a composi ion in adul
women wi h obesi y, leading o modes changes in hos me abolism [
106
]. Finally, he
new in eg an o he “bio ics” amily, pos bio ics, means o ela es wi h he pas eu ized
e sion o p obio ics o po ions o mic obial s ains holding heal h-p omo ing e ec s [
107
].
A pilo ial o pas eu ized A. muciniphila and i s memb ane p o ein Amuc_1100 showed
posi i e e ec s on human me abolism indica o s [
102
,
108
]. This p o ein eco e s gu ba ie
unc ions wi h augmen ed goble cell densi y by oll-like ecep o 2 and mode a ely epea s
he bene icial e ec o li e bac e ium A. muciniphila on insulin sensi i i y and ene gy
me abolism [102,108].
6. Pe o mance: Gu Mic obio a P o ile in A hle es
P o essional a hle es a e a speci ic popula ion wi h e iden di e ences in mic obio a
composi ion when compa ed wi h he non-a hle e popula ion [
109
]. Se e al s udies ha e
demons a ed he associa ion be ween gu mic obio a and bo h physical ac i i y and ex-
e cise [
110
]. Di e ences a e ma ked also acco ding o di e en a hle es cha ac e is ics as
well as hei body composi ion [
111
]. A hle e gu mic obio a shows he highes alpha di-
e si y in compa ison wi h obesi y pa ien s being associa ed wi h se e al isk ac o s [
112
].
Impo an ly, ca dio espi a o y i ness (a powe ul indica o o a hle ic pe o mance and
heal h) has been associa ed o Fi micu es/Bac e oide es a io in heal hy young adul s,
and hese associa ions we e independen o die composi ion, demons a ing ha gu
mic obio a di e si y depends on he le el o physical i ness o he popula ion [
113
]. On
he o he hand, a hle es’ cha ac e is ics a e also a ac o ela ed o hei mic obio a com-
posi ion [
109
]. Speci ically, di e ences a e e iden in ugby a hle es ha show a highe
p opo ion Akke mansia genus han a g oup wi h an ele a ed BMI [33]. Mo eo e , he Bac-
e oides o P e o ella a io is di e en be ween endu ance (ca dio ascula exe cise pe o med
o an ex ended pe iod) aining elde ly subjec s and heal hy con ols [
114
]. In e es ingly,
bac e ial genus Veillonella was ela ed o exe cise changes in a hle es a e unning he
Bos on Ma a hon [
115
], sugges ing ha exe cise changes ela ed o mic obio a include
enzyma ic p ocesses ela ed o lac a e p oduc ion. Mo eo e , a p o essional cyclis shows a
highe abundance in axa ela ed o exe cise loads, such as P e o ella and Me hanob e ibac e
smi hii, which could be ela ed o posi i e consequences o exe cise o pe o mance and
a hle ic heal h [45].
Finally, Dono an e al. [
116
] s udied he mic obio a composi ion acco ding o di e en
g oups o spo s and ound di e ences in ela i e abundance ac oss i e species, namely,
Polynucleobac e necessa ies,Eubac e ium ec ale,B. ulga us,F. p ausni zii, and Go donibac e
massiliensis. In e es ingly, he classi ica ion was based on dynamic (mo e ela ed o aug-
men ed ca diac ou pu ) and inac i e componen s (mo e associa ed wi h inc easing he
Nu ien s 2021,13, 3999 8 o 15
maximal olun a y con ac ion) [
116
,
117
]. They ound ha hose pa icipa ing in high
dynamic spo ha e a bigge abundance o Lac obacillus acidophilus,Bi idobac e ium animalis,
F. p ausni zii, and P e o ella in e media, while a hle es wi h bo h s a ic componen s and
high dynamic we e ela ed o a g ea e Bac e oides caccae abundance. Thus, he au ho s
ha e indica ed ha he di e ences in abundance ac oss g oups may be a esul o he
speci ic cha ac e is ics o spo s, p incipally ela ed o he p oduc ion o c ea ine, lac a e,
and subs an ial muscle u no e [118].
7. Fu he Pe spec i es
The WHO anked physical inac i i y as he ou h p incipal isk elemen o global
mo ali y. In con as , egula and adequa e physical ac i i y le els d op he mo ali y
a e p oduced by some ch onic diseases. Fo ins ance, physical exe cise bene i s he
p e en ion o se e al obesi y- ela ed diso de s such as dyslipidemia, insulin esis ance,
and hype ension, educing in ahepa ic lipid [119].
Addi ionally, exe cise may posi i ely con ol gu mic obio a in immune-based and
ch onic diseases. In ac , exe cise can p o oke quali a i e and quan i a i e changes in
mic obial composi ion in humans [
120
]. In addi ion, a de e io a ed mic obio a p o ile
may con ibu e o he e iopa hogenesis o obesi y [
121
]. Acco dingly, he e is a concep ual
amewo k in which s udies on exe cise in he e e sion o hype calo ic die s e ec s and
obesi y by modula ing mic obio a a e gaining momen um wi hin he scien i ic commu-
ni y. Howe e , unsol ed ques ions emain open conce ning he complex nexus be ween
mic obio a, heal h main enance, and obesi y, and e en mo e, he exe cise in ensi y, ype,
du a ion, o doses emains a con o e sial issue. Fo example, i is likely he impac o
exe cise on he mic obio a would no be he same i i is p ac iced as a habi o main ain
weigh and heal h, in ensi ely as a high-le el a hle e, o as a weigh -loss s a egy wi h o
wi hou calo ic es ic ion. In consequence, he exe cise e ec s on he mic obio a canno be
conside ed globally as he e a e many a iables o conside in his equa ion depending on
he ul ima e pu pose o he exe cise. Mo eo e , i is also necessa y o conside ha exe cise
p o okes unique mic obio a p o iles acco ding o he hos cha ac e is ics. Fu he mo e,
he a ge exe cise popula ion should be conside ed, no only he baseline physical i ness
and he p esence o absence o unde lying diseases bu also he age, sex, and me abolic
and ho monal s a us o he indi idual. A his poin , i should be no ed whe he women
a e pos - o p e-menopausal since i is one o he main con olle s o ci cula ing es ogens
in he gu mic obio a [
122
]. In consequence, he implied me abolic pa hways could no
be he same and he e o e nei he could be hei impac on he mic obio a. Fu he , he
close connec ion be ween he b ain and he gu mic obio a ( he “gu –b ain axis”) should
also be conside ed. In his ega d, some pieces o e idence show ha he e is an ele a ed
ela ionship be ween emo ional and physical s ess h oughou exe cise and modi ica ions
in gas oin es inal mic obio a composi ion [
123
], bu i is ye unsol ed whe he exe cise
modi ies men al heal h, which is sugges ed by modi ica ions in he gu –b ain axis o he
obse ed imp o emen in men al heal h due o exe cise-induced changes in he mic obio a.
Figu e 1summa izes he main in o ma ion desc ibed in he p esen manusc ip .
Nu ien s 2021,13, 3999 9 o 15
Nu ien s 2021, 13, x FOR PEER REVIEW 9 o 15
in he mic obio a. Figu e 1 summa izes he main in o ma ion desc ibed in he p esen
manusc ip .
Figu e 1. Impac o exe cise on gu mic obio a in obesi y. Abb e ia ions: BCAA, b anched-chain amino acids; FXR, a -
nesoid X ecep o ; LPS, lipopolysaccha ide; GLP-1, Glucagon-like pep ide 1; GPCRs, G-p o ein-coupled ecep o s;
GPR119, G p o ein-coupled ecep o 119; PYY, Pep ide YY; UCP-1, Uncoupling p o ein 1; TGR5, G-p o ein-coupled bile
acid ecep o , TLR2, oll-like ecep o 2.
8. Conclusions
In es inal mic obio a ac as a signi ican playe in obesi y p og ession. Physical ac i -
i y po en ially bene i s obesi y h ough changes in mic obio a composi ion. Mic obio a,
exe cise, and die a y habi s ha e a complex ela ionship. Acco dingly, i is manda o y o
e alua e he possible in luence o exe cise and speci ic die s, oods, nu ien s, o supple-
men s on mic obial di e si y in he gu . The changes o gu mic obio a s imula ed by
physical exe cise depend on he basal physiological s a e and maybe condi ioned by pa-
ame e s, such as age o BMI. Fu he in es iga ion is needed o elucida e he unde lying
mechanisms.
Au ho Con ibu ions: J.A.-V., P.S.-U., F.J.R.-O., A.I.Á.-M., J.O.-A. and J.P.-D. pa icipa ed in he
bibliog aphic sea ch, discussion, and w i ing o he manusc ip . All au ho s ha e ead and ag eed
o he published e sion o he manusc ip .
Funding: This esea ch ecei ed no ex e nal unding.
Ins i u ional Re iew Boa d S a emen : No applicable.
Figu e 1.
Impac o exe cise on gu mic obio a in obesi y. Abb e ia ions: BCAA, b anched-chain amino acids; FXR, a nesoid
X ecep o ; LPS, lipopolysaccha ide; GLP-1, Glucagon-like pep ide 1; GPCRs, G-p o ein-coupled ecep o s; GPR119, G
p o ein-coupled ecep o 119; PYY, Pep ide YY; UCP-1, Uncoupling p o ein 1; TGR5, G-p o ein-coupled bile acid ecep o ,
TLR2, oll-like ecep o 2.
8. Conclusions
In es inal mic obio a ac as a signi ican playe in obesi y p og ession. Physical ac i -
i y po en ially bene i s obesi y h ough changes in mic obio a composi ion. Mic obio a,
exe cise, and die a y habi s ha e a complex ela ionship. Acco dingly, i is manda o y
o e alua e he possible in luence o exe cise and speci ic die s, oods, nu ien s, o sup-
plemen s on mic obial di e si y in he gu . The changes o gu mic obio a s imula ed
by physical exe cise depend on he basal physiological s a e and maybe condi ioned by
pa ame e s, such as age o BMI. Fu he in es iga ion is needed o elucida e he unde lying
mechanisms.
Au ho Con ibu ions:
J.A.-V., P.S.-U., F.J.R.-O., A.I.Á.-M., J.O.-A. and J.P.-D. pa icipa ed in he
bibliog aphic sea ch, discussion, and w i ing o he manusc ip . All au ho s ha e ead and ag eed o
he published e sion o he manusc ip .
Funding: This esea ch ecei ed no ex e nal unding.
Ins i u ional Re iew Boa d S a emen : No applicable.
In o med Consen S a emen : No applicable.