Ci a ion: Cinca-Mo os, S.;
Ál a ez-He ms, J. The Impo ance o
Main aining and Imp o ing a Heal hy
Gu Mic obio a in A hle es as a
P e en i e S a egy o Imp o e Hea
Tole ance and Acclima iza ion.
Mic oo ganisms 2024,12, 1160.
h ps://doi.o g/10.3390/
mic oo ganisms12061160
Academic Edi o : P amod Gopal
Recei ed: 17 Ap il 2024
Re ised: 4 June 2024
Accep ed: 5 June 2024
Published: 6 June 2024
Copy igh : © 2024 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/).
mic oo ganisms
Re iew
The Impo ance o Main aining and Imp o ing a Heal hy Gu
Mic obio a in A hle es as a P e en i e S a egy o Imp o e Hea
Tole ance and Acclima iza ion
Se gi Cinca-Mo os 1,2,* and JesúsÁl a ez-He ms 3
1Mic o luidics Clus e UPV/EHU, Analy ical Mic osys ems & Ma e ials o Lab-on-a-Chip (AMMa-LOAC)
G oup, Analy ical Chemis y Depa men , Uni e si y o he Basque Coun y UPV/EHU,
01006 Vi o ia-Gas eiz, Spain
2
Mic o luidics Clus e UPV/EHU, BIOMICs Mic o luidics G oup, Lasca ay Resea ch Cen e , Uni e si y o he
Basque Coun y UPV/EHU, 01006 Vi o ia-Gas eiz, Spain
3Physiology and Molecula Labo a o y (Phymolab), 40170 Collado He moso, Spain; [email p o ec ed]
*Co espondence: [email p o ec ed]; Tel.: +34-686475163
Abs ac : Exposu e o passi e hea (acclima ion) and exe cise unde ho condi ions (acclima iza ion),
known as hea acclima ion (HA), a e me hods ha a hle es include in hei ou ines o p omo e as e
eco e y and enhance physiological adap a ions and pe o mance unde ho condi ions. Despi e
he po en ial posi i e e ec s o HA on heal h and physical pe o mance in he hea , hese s imuli
can nega i ely a ec gu heal h, impai ing i s unc ionali y and con ibu ing o gu dysbiosis. Blood
edis ibu ion o ac i e muscles and pe iphe al ascula iza ion exis du ing exe cise and HA s im-
ulus, p omo ing in es inal ischemia. Gas oin es inal ischemia can impai in es inal pe meabili y
and agg a a e sys emic endo oxemia in a hle es du ing exe cise. Sys emic endo oxemia ele a es
he immune sys em as an in lamma o y esponses in a hle es, impai ing hei adap i e capaci y o
exe cise and hei HA ole ance. Be e gu mic obio a heal h could bene i exe cise pe o mance
and hea ole ance in a hle es. This a icle sugges s ha : (1) he in es inal modi ica ions induced by
hea s ess (HS), leading o dysbiosis and al e ed in es inal pe meabili y in a hle es, can dec ease
heal h, and (2) a p e iously acqui ed mic obial dysbiosis and/o leaky gu condi ion in he a hle e
can nega i ely exace ba e he sys emic e ec s o HA. Main aining o imp o ing he heal hy gu
mic obio a in a hle es can posi i ely egula e he in es inal pe meabili y, educe endo oxemic le els,
and con ol he sys emic in lamma o y esponse. In conclusion, s a egies based on posi i e daily
habi s (nu i ion, p obio ics, hyd a ion, ch ono egula ion, e c.) and p e en ing mic obial dysbio-
sis can minimize he po en ially undesi ed e ec s o applying HA, a o ing he mo ole ance and
pe o mance enhancemen in a hle es.
Keywo ds: acclima ion/acclima iza ion, hea s ess; gu mic obio a; in es inal dysbiosis; in es inal
pe meabili y; a hle es
1. In oduc ion
O e he las decades, a hle es ha e s a ing o include di e en s a egies o passi e
and ac i e exe cise in ho condi ions (passi e hea ) o p omo e eco e y and he mo-
ole ance in subsequen exe cise in he hea [
1
–
4
]. Exposu e o hea p omo es adap i e
esponses o acclima ion o acclima iza ion, depending on whe he he exposu e occu s
in a i icial (acclima ion) o na u al (acclima iza ion) wa m en i onmen s [
1
]. Hea ac-
clima ion/acclima iza ion, he ea e HA, is used among a hle es o p o ec heal h and
imp o e pe o mance in ho en i onmen s [
1
]. Long- e m HA s a egies, which include
egula passi e o ac i e hea exposu e o mo e han 10 days, achie e he bes esul s
compa ed o sho - e m in e en ions [
4
]. To da e, he e ha e been a la ge numbe o
p o ocols and guidelines desc ibed o long- e m HA p ocedu es [
3
–
7
]. Du ing exe cise in
Mic oo ganisms 2024,12, 1160. h ps://doi.o g/10.3390/mic oo ganisms12061160 h ps://www.mdpi.com/jou nal/mic oo ganisms
Mic oo ganisms 2024,12, 1160 2 o 15
he hea , p ema u e exhaus ion and shock due o hea s ess (HS) can be common in a hle es
no acclima ized o hea and a e he esul o a complex combina ion o hea cy o oxici y
(including endo oxemia om he gu ), impai ed coagula ion, and sys emic in lamma o y
esponse synd ome (SIRS), which is ollowed by de e io a ion o o gan esponses and
ul ima ely, educed physical pe o mance. The p e en ion o hea s ess is now conside ed
o be mo e bene icial han ea ing he condi ion. The e o e, p o iding s a egies ha
p omo e he p e en ion o p ema u e hea a igue would be o in e es o a hle es, coaches,
and scien is .
Biologically, p olonged and in ense exe cise ele a es body empe a u e, p omo ing
blood edis ibu ion o ac i e muscles, which educes in es inal blood low by 80% [
8
]. This
e ec p omo es in es inal ischemia ha exace ba es damage o he epi helial cells and igh
junc ion p o eins making up he in es inal mucosa’s physical ba ie [
9
]. The gas oin es inal
(GI) ac exhibi s key unc ions in main aining whole-body homeos asis and heal h. The
GI ac is he o gan di ec ly esponsible o abso bing nu ien s, and i ac s as a physical
and immunological ba ie agains he en y o noxious compounds in o he in e io
milieu [
10
]. Impai men o he gu ba ie in eg i y is o en in ol ed in a ious GI and
ex a-GI diseases, esul ing in educed physical pe o mance. On he o he hand, he gu
mic obio a (GM) colonize he GI ac and de elop mul iple sys emic unc ions o he hos
a diges i e [
11
,
12
], me abolic [
11
,
12
], immunological [
11
–
13
],
homeos a ic [11,12,14–16]
,
and s uc u al [
11
,
12
] le els. In ac , he GM is di ec ly in ol ed in main aining he
epi helial ba ie in eg i y h ough bac e ial ac i i y, p oducing and syn hesizing mucus
and sho -chain a y acids (SCFAs) [
11
,
12
,
17
]. Thus, he GM in e ac s di ec ly wi h he
immune and neu al sys ems h ough me aboli es and ne es (gu –b ain axis), modula ing
he in lamma o y esponse, and p e en ing ha m o he in es inal ba ie [
13
]. Fu he mo e,
he GM con ibu es o main aining he app op ia e in es inal pH, empe a u e, and oxygen
le els o di e en s uc u es o he in es ine [
11
,
12
,
14
–
16
]. Main aining a heal hy gu
mic obio a can be achie ed by main aining a highe di e si y, s abili y, and balance o
he bac e ial ecosys em [
18
]. Fo a hle es, main aining a heal hy GM is key o p omo ing
adap i e bene i s ha p e en abe an esponses such as hose occu ing du ing a s a e
o gu dysbiosis, cha ac e ized by local in lamma ion, leaky gu synd ome, and impai ed
me abolic and endoc ine unc ions [
19
]. In his ega d, he he apeu ic ole o main aining
a heal hy gu mic obio a (GM) has also been epo ed in he p e en ion o hea s oke
h ough he de e ence o sys emic endo oxemia [20].
Con e sely, he imbalance o he GM is de ined and desc ibed in he li e a u e as
a dysbiosis ha con ibu es o a wo sening o he symbio ic unc ions in he hos [
17
].
Such a condi ion can be eached ollowing exposu e o di e en s ess ul s imuli and
nega i ely esul om a li e s yle ha includes poo nu i ion, exposu e o oxics and pollu-
ion, ch onodis up ion, ce ain acqui ed pa hologies, and seden a ism [
21
]. An abe an
consequence o gu dysbiosis is leaky gu synd ome, in which in es inal pe meabili y is
impai ed, esul ing in he highe ansloca ion o bac e ia and oxins om he gu in o he
bloods eam (endo oxemia) [
22
–
24
]. Sys emic endo oxemia esul s in a sys emic in lam-
ma o y and immune esponse ha di ec ly impai s heal h and physical pe o mance [
25
].
Thus, he ch onici y o sys emic in lamma ion and immune o e eac ion can lead o a
nega i e physiological spi al, comp omising bo h he heal h and physical pe o mance
o a hle es [
26
]. The pa hophysiology occu ing du ing hea exposu e can be agg a a ed
when a hle es su e om a s a e o GM dysbiosis. In his ega d, Cos a e al. [
27
] desc ibe
how imp o ing he balance o he gu mic obio a (GM) in a hle es, including epi helial
ba ie heal h, could imp o e he sys emic s a e du ing exe cise in he hea , dec easing
he in lamma o y esponse and endo oxemia induced by he gu . In a s, Cao e al. [
28
]
demons a ed ha imp o ing he gu mic obiome balance and i s unc ions in ega ds o
gu ba ie in eg i y (mucus, cell in eg i y, and selec i e pe meabili y) induced p o ec i e
p ope ies unde hea s ess. The mucus laye ac s as an impo an mechanism o p o-
ec ing he hos agains mic obial in ade s and con ibu es o he mu ualism be ween he
hos and he mic obes [
29
]. The loss o mucus laye hickness would be a consequence, as
Mic oo ganisms 2024,12, 1160 3 o 15
well as a p ecu so o bo h nega i e as maladap i e esponses o HA and o he physically
ele a ed demands in a hle es.
The e o e, a hle es mus ake in o conside a ion hei own sys emic heal h [
30
], in-
cluding hei GM balance and he in eg i y o hei GI unc ions p io o including highly
speci ic aining me hods, such as HA. Fu u e s udies equi e he in es iga ion o di ec
s a egies ha p e en and ea GI complica ions p oduced by ex eme en i onmen al
condi ions such as hea [31] o al i ude [32].
He e, we in es iga e he di ec consequences induced by a s a e o GM dysbiosis on
maladap i e esponses su e ed by a hle es exposed o HS. The main goal o he p esen
s udy is o highligh he impo ance o main aining a heal hy GM balance in a hle es as
a he apeu ic ea men , which can speci ically con ibu e o he p e en ion o p ema u e
a igue du ing HS exposu e and exe cise.
2. Hea S ess S imulus and Gu Dysbiosis in A hle es
The physical p epa a ion o high-pe o mance a hle es is e y di icul and includes
epea ed highly speci ic and in ense s imulus (ele a ed consump ion o simple ca bohy-
d a es [
30
] and p o eins [
33
], hypoxic exposu e and aining [
34
], and hea exposu e and
aining [
4
]). Ex ensi e e idence has shown ha hea exposu e (ac i e and passi e) can
p omo e heal h and physical pe o mance bene i s [
3
,
32
–
34
]; howe e , he speci ic h esh-
old ha nega i ely a ec s heal h has no been comple ely explo ed. Un il ecen ly, mos
esea ch on his opic has ocused on how hea s ess p omo es in es inal al e a ions, such
as bu ns, in pa ien s wi h hea - ela ed pa hologies [
35
–
37
]. Howe e , hese speci ic in e -
en ions equi e e icien sys emic esponses o main ain and/o imp o e physiological
pe o mance unde such s ess. The main enance o he sys emic heal h o a hle es is he
main ac o o ob aining he bene i s o hese speci ic in e en ions [
30
]. Fo example, in a
sys emic con ex , whe e a hle es expe ience a decline in heal h due o ch onic s ess, highe
le els o immune esponse and in lamma ion inc ease he allos a ic load and can induce
mo e physiological damage, impai ing physical pe o mance. I is impo an , he e o e, o
unde s and he mechanisms ha imp o e adap i e esponses in bo h he sho and long
e m, including a heal hy GM and i s communica ion wi h he a hle e’s o ganisms.
The inc eased plasma endo oxemia om leaky gu synd ome is suspec ed o be an
impo an e iological ac o in he ci cula o y shock ha accompanies p ema u e HS in ol-
e ance in humans [
38
]. The exposu e o HS and maximal exe cise agg a a es endo oxemia
in he con ex o impai ed gu pe meabili y, possibly due o he educ ion o hepa ic de oxi-
ica ion. Du ing HA and exe cise, he educ ion o po al ein blood low, combined wi h
he mally al e ed hepa ocy e unc ion, se e ely educes he capaci y o de oxi y a su ge o
endo oxin [39].
The non-adap i e e ec s o HS on pe o mance and heal h ha e been ela ed o
exace ba ed ca dio ascula , me abolic, and ho monal esponses [
7
]. A he gu le el, HS
can lead o leaky gu synd ome, which is associa ed wi h in es inal ischemia. Du ing HA
and exe cise, a sys emic blood low edis ibu ion om splanchnic and enal ascula beds
o he muscula and cu aneous ascula beds exis s, ensu ing an adequa e ene gy and
oxygen supply o he ac i e muscles and acili a ing hea dissipa ion [
40
]. Howe e , gu
ischemia and i s consequen hypoxia inc eases me abolic s ess [
41
], which di ec ly al e s
he s uc u e o he en e ocy e memb ane [
22
], in ol ing igh junc ions (TJs), which become
damaged, allowing o he ansloca ion o lipopolysaccha ides (LPS) om G am-nega i e
bac e ia (mainly p o eobac e ia) in o he ci cula ion [
22
]. G am-nega i e bac e ia ound
in he small and la ge in es ine a e ha m ul o he body due o an endo oxin uni loca ed
in he bac e ial ou e memb ane [
23
]. This ansloca ion o LPS om he luminal side o
he bloods eam s imula es a sys emic immune esponse cha ac e ized by he elease o
p oin lamma o y cy okines IL-6 and TNF-
α
[
42
]. I also ac i a es inna e immune p oduc ion
(ci cula ing monocy es and issue mac ophages like Kup e cells) o an i-in lamma o y
cy okines IL-1 [
43
]. This in lamma o y esponse u he a ec s igh junc ions, which show
inc eased leakage o bac e ial LPS on he basola e al side [
44
]. Along wi h he cy o oxic
Mic oo ganisms 2024,12, 1160 4 o 15
e ec s o hype he mia p oduced by HS and exe cise i sel , dehyd a ion o en exace ba es
hese e ec s, comp omising he he mo egula o y capaci y [
45
]. This si ua ion u he
agg a a es pe meabili y, and he blood LPS concen a ion eaches a h eshold ha can
igge a sys emic in lamma o y esponse (SIR) (see Figu e 1) [39].
Figu e 1. Hea s ess (HS) aining and exposu e p omo e ischemia in he in es ine h ough he
blood edis ibu ion o ac i e muscles and ascula essels. The main goal o he body du ing HS
is main ain homeos a ic empe a u e. Gu dysbiosis is a nega i e heal h condi ion o he body,
impai ing symbio ic unc ions o he mic obio a and agg a a ing in es inal dys unc ions, p esen ing
as impai ed gu pe meabili y. Gu pe meabili y dys unc ion allows o he passage o endo oxins
in o he blood, inc easing he sys emic in lamma o y esponse and educing he ime o exhaus ion
du ing exe cise in a ho en i onmen .
P e ious s udies ha e shown ha a hle es who main ain a heal hy gu homeos asis
can pe o m physical ac i i y ee o ad e se hea - ela ed consequences, ole a ing highe
co e empe a u es (Tc), e en up o 42
◦
C [
46
–
49
]. In his con ex , esea ch s udies ha e
p oposed di e en p e en i e measu es, ocusing on minimizing he sys emic e ec s o
inc eased body empe a u e [
50
–
52
]. Howe e , no p e ious s udies ha e sugges ed ha
a hle es who imp o e hei GM heal h could p ese e hei in es inal unc ions and educe
he p ema u e hea -shock and/o sys emic ailu e induce by exace ba ed endo oxemia and
in lamma ion de i ed om he gu . These p e en i e ac o s ela ed o gu heal h may play
a c ucial ole in he pa hophysiology o HS beyond he e ec s o hea s ess, as sugges ed
by p e ious esea ch [
26
,
53
,
54
]. In his ega d, A ms ong e al. [
39
] p oposed ha highe
ole ance o mode a e le els o LPS p oduced du ing HS and maximal exe cise could be a
Mic oo ganisms 2024,12, 1160 5 o 15
plausible explana ion o he supe io ole ance o endo oxemia in a hle es acclima ized
o hype he mia.
In he sho - e m, acu e HS appea s no o a ec he di e si y and abundance o p o-
ec i e commensal bac e ia ( hose mo e a o able o hos gu heal h, such as Lac obacillus,
Bi idobac e ium,S ep ococcus,Akke mansia muciniphyla,Faecalibac e ium p ausni zii,Rosebu ia,
o Eubac e ium) [
55
–
58
]. Howe e , applying ch onic passi e and ac i e hea du ing HA
s imuli in a hle es may agg a a e leaky gu synd ome and po en ia e sys emic endo ox-
emia. This could igge sys emic in lamma ion simila o ha obse ed in pa hologies
associa ed wi h hea s ess and signi ican ly impai physical pe o mance (see Figu e 1).
In es inal mic oo ganisms a e sensi i e o changes in sys emic empe a u e. The inc ease in
in e nal empe a u e de i ed om exe cise in HA could enhance he eme gence o po en ial
pa hogens ha would di ec ly exace ba e dysbiosis, in es inal leaky gu synd ome, and
consequen ly, sys emic endo oxemia and in lamma ion (see Figu e 2). I has been epo ed
ha each bac e ium equi e a speci ic en i onmen al milieu o li e and g ow h adequa ely.
In his ega d, some pa hogenic bac e ia, such as Esche ichia coli and o he membe s o he
En e obac e iaceae amily, a e he mo ole an , able o su i e a empe a u es bo h coole
and wa me han hose o he ypical endo he mic hos . Ye sinia en e opa hogenic can g ow
a empe a u es close o 0
◦
C [
59
], while labo a o y s ains o Esche ichia coli can g ow
be ween app oxima ely 8
◦
C [
60
] and 42
◦
C, and adap o g ow a empe a u es o 48
◦
C o
highe [
61
]. Membe s o he P o eobac e ia phylum a e conside ed unc ionally lexible in
esponse o a ious en i onmen al s esses. Speci ically, pa hogens like Salmonella,Ye sinia,
Pseudomonas, and pa hogenic Esche ichia coli use hos empe a u e as an en i onmen al cue
o up egula e he i ulence genes [
62
–
64
]. These genes espond mo e s ongly o e e -like
empe a u es, such as 42
◦
C, han o empe a u es below 37
◦
C [
64
], and an enzyme in
Pseudomonas ae uginosa shows inc eased e iciency up o 45
◦
C [
64
]. Clos idioides di icile,
ano he ele an in es inal pa hogen, g ows equally well a 37
◦
C and 41
◦
C
in i o
[
65
,
66
].
In a s udy using g owing pigs subjec ed o ch onic hea s ess, in es inal dysbiosis and
inc eased pe meabili y we e obse ed, cha ac e ized by an inc ease in he p esence o
po en ial pa hogens like As e oleplasma,Shu lewo hia, and Mycoplasma. Addi ionally, a
supp ession o bene icial bac e ia species such as Cop ococcus and Ae isca do ia, which a e
associa ed wi h in es inal immune unc ion, was obse ed [67].
Figu e 2. Hea s ess can lead o gu dysbiosis h ough he ele a ion o ce ain he mo ole an bac e ia,
while educing o he bene icial bac e ia. The educ ion o blood pe usion du ing exe cise p oduces
ischemia hypoxia in he gu , possibly inc easing he GM dysbiosis and exace ba ing he e ec s o
hea s ess du ing exe cise.
Mic oo ganisms 2024,12, 1160 6 o 15
3. Could Gu Heal h Imp o e Hea S ess Tole ance in A hle es?
The use o bioma ke s o moni o HS esponse (molecula , physiological, and beha -
io al) can be a aluable ool o assessing an a hle e’s esilience unde such condi ions. To
main ain homeos asis du ing HS, a hle es igh o adjus hei physiological and beha io al
esponses o posi i ely adap . The egula s imulus o hea exposu e in a hle es possibly
al e s he beha io al esponses, including ood and hyd a ion in ake, he equency and
du a ion o sleep, and no mal ac i i ies, including es ing. F om a molecula pe spec i e,
bioma ke s such as hea shock p o ein 60 [
39
] o in e leukins [
35
] a e being used o moni o
he esponse o HS. Thus, GM analysis could also be used as a bioma ke con ibu ing o
an ea ly diagnosis o HS in ole ance by de ec ing GM dysbiosis. [68].
The gu is one o he majo a ge o gans a ec ed by speci ic in e en ions caused
by exe cise, al i ude, nu i ion, and hea s ess. High-in ensi y exe cise and HA p omo es
damage o he mucosal epi helia, inc easing immune ac i i y and leaky gu synd ome.
Mo eo e , HS p omo es changes in ega ds o GM di e si y [
69
]. Recen s udies ha e
sugges ed ha hea acclima iza ion imp o es physiological pe o mance du ing HS h ough
sys emic esponses, bu his may also be ela ed o GM adap a ion [
55
]. I has been shown
ha a e HA, a signi ican dec ease in po en ially pa hogenic bac e ia occu s, whe eas
bene icial bac e ia inc ease signi ican ly [
9
,
55
,
70
]. The e o e, op imizing bene icial bac e ial
pheno ypes om he GM ( o example, highe le els o bac e ial p ecu so s o e icien gu
pe meabili y, sho -chain a y acid p oduc ion, seconda y bile acid p oduc ion) con e s
po en ial bene i s o esponding and adap ing o HS and physical exe cise. In e en ions
ocused on p ecise nu i ion and p obio ic in ake [
55
,
71
] could be necessa y when a hle es
include hea exposu e du ing hei aining and compe i i e ou ines.
3.1. Speci ic Nu i ion and Hyd a ion Balance o Imp o e Gu Heal h and HA Tole ance
in A hle es
The loss o bac e ial homeos asis in he gu (dysbiosis), wi h he p esence o impai ed
epi helial pe meabili y (leaky gu synd ome), is a ca as ophic condi ion o a hle es because
i can inc ease hei isk o su e ing p ema u e a igue du ing HA and/o maximal exe -
cise [
72
]. The e o e, imp o ing and op imizing he unc ionali y associa ed wi h a heal h
in es inal ba ie possibly dec eases HS shock and inc eases ole ance. In his ega d, he
main s imulus o changing he gu ecosys em and i s unc ionali y is die and hyd a ion.
F om ou pe spec i e, hyd a ion should also be emphasized, especially in con ex
whe e gu dysbiosis combines wi h hea s ess (HS) because dehyd a ion can be an ag-
g a a ing ac o o HA [
45
]. This leads o a loss o he mo egula o y capaci y, u he
inc eases co e empe a u e (Tc), and damages he epi helial ba ie . A s a e o dehyd a ion
can exace ba e undesi ed HS esponses. In ac , Lambe e al. [
45
] epo ed ha he loss o
luid balance du ing unning exe cise p oduced g ea e in es inal pe meabili y han ha
ound in a hle es ha main ained adequa e hyd a ion du ing he ace, e en wi h alues
simila o hose a es , i losses due o swea we e compensa ed. Thus, a disbalance o
hyd a ion con ibu es o educe in es inal blood low, agg a a ing in es inal pe meabili y
and impai ing physical pe o mance [45].
I is impe a i e o emphasize he impo ance o adequa e nu i ion o p omo e GM
heal h and educe he possibili y o induced in es inal dysbiosis [
13
]. Se e al s udies ha e
in es iga ed how die s ich in sa u a ed a s [
73
,
74
] and suga s [
75
] dec ease GM di e si y
and impai in es inal pe meabili y. In his sense, Pendyala e al. [
76
] demons a ed how
a Wes e n-s yle die ich in a s and ca bohyd a es inc eased endo oxemia o igina ing in
he in es ine by 71%, while a die lowe in a s and ca bohyd a es educed hese le els
by 31%. Among suga s, i has been shown ha he excessi e consump ion o uc ose is
ela ed o impai men o he in es inal ba ie [
77
,
78
]. While e ined suga s p omo e he
g ow h o oppo unis ic bac e ia such as Clos idium di icile [
79
] and pe ingens due o
inc eased bile p oduc ion [
80
], complex ca bohyd a es inc ease le els o bene icial species
such as Bi idobac e ia spp., B.longum subspecies longum,B.b e e, and B. he aio aomic on [
81
].
Vege a ian die s p e en he g ow h o po en ially pa hogenic bac e ia such as E. coli and
Mic oo ganisms 2024,12, 1160 7 o 15
o he membe s o he En e obac e iaceae amily [
82
]. This is due o he g ea e amoun
o ibe ha his ype o die con ains, which causes g ea e p oduc ion o sho -chain
a y acids (SCFA) by in es inal bac e ia, as well as a dec ease in in es inal pH [
82
]. Fibe
consump ion seems o be ano he key aspec o main aining gu eubiosis. In his ega d,
Filippo e al. [
83
] epo ed ha he GM o Eu opean child en is educed in Bac e oide es and
en iched in En e obac e iaceae compa ed o he GM o A ican child en o u al o igin. The
main di e ence be ween he die o Eu opean and A ican child en is associa ed wi h ibe
consump ion. The consump ion o la onoids o plan o igin, such as que ce in p esen in
g apes and onions, which inc ease epi helial esis ance and he exp ession o claudin-4 in
epi helial cells [84], can con ibu e o he p o ec ion agains in es inal pe meabili y.
The e o e, abo e desc ip ion indica es ha nu i ion is key o main aining GM heal h
and a oiding o co ec ing dysbiosis. A hle es mus aim o a oid he excessi e egula
consump ion o suga s and sa u a ed a s, limi he in ake o animal p o eins, and inc ease
ibe consump ion. On he o he hand, he s imulus o as ing o e nigh o 14 o 16 h has
demons a ed e ec i eness in p omo ing in es inal homeos asis, educing in lamma ion,
and egene a ing he mucosal ba ie [
85
]. I is ecommended o use as ing as a s a egy
p io o he applica ion o con olled hype he mic s imuli, o a leas main ain a minimum
in e al o 4 h om he las in ake o ood be o e s a ing he he mal s imulus, whe eby
in es inal mo ili y is educed [86].
3.2. The E ec o P obio ics, P ebio ics, Vi amins, and Sho -Chain Fa y Acids on Gu Heal h o
Imp o e P e-Acclima iza ion and Hea Tole ance in A hle es
He e, we p opose ha inc easing bene icial bac e ia o main ain good pe meabili y
could imp o e p ema u e hea shock in a hle es exposed o hea condi ions and du ing
maximal exe cise. The in ake o p obio ics has demons a ed p o ec i e bene i s in ega ds
o gu heal h and a hle ic pe o mance [
87
]
.
In his con ex , i appea s ha p obio ic
supplemen a ion may mi iga e he ad e se e ec s o hea exposu e when implemen ed o
a p olonged du a ion. Li le esea ch exis s on he opic; howe e , Gill e al. [
88
] demon-
s a ed ha supplemen a ion wi h a p obio ic d ink con aining Lac obacillus casei du ing
wo hou s o unning a 34
◦
C did no signi ican ly imp o e endo oxemia and ele a ed
cy okine le els caused by HS. Howe e , Shi e al. [
56
] epo ed ha main aining p obio ic
supplemen a ion o 4 weeks and inc easing he dose (con aining 45 billion CFU o Lac o-
bacillus, Bi idobac e ium, and S ep ococcus) could e ec i ely educe he inc eased le el o
LPS caused by a hle es exe cising a high empe a u es. Gi en he small numbe o s udies
on his opic, i is necessa y o u he explo e whe he p obio ic supplemen a ion can
signi ican ly imp o e HS- ela ed discom o . Be o e making ecommenda ions o a hle es,
i is he e o e impo an o conside : (1) he ype and dosage o p obio ics, acco dingly he
indi idual GM, and (2) he indi idual ac o s ega ding he hos lo a s a us (di e si y)
and he HS s imuli ha he a hle e can wi hs and o be e de ine he in e ening ole o
p obio ics [87].
The e o e, i may be essen ial o ecommend ha a hle es es hei GM p io o includ-
ing an HA s a egy. The analysis o key bac e ia ela ed o gu ba ie homeos asis, mucosal
p oduc ion, and egene a ion would be impo an . The e a e ce ain p o ec i e bac e ia
which ha e been accep ed as bioma ke s o heal hy gu ba ie pe meabili y (Akke mansia
muciniphyla,Faecalibac e ium p ausni zii,Rosebu ia, and some species o Eubac e ium) [
57
,
58
].
Depending on he mucosal ela ed-bac e ia p opo ions, he p e- and p obio ic in e en ion
and die could be indi idualized and p oposed. We ha e obse ed ha eli e endu ance a h-
le es exp essing high le els o Faecalibac e ium p ausni zii and Rosebu ia p io o endu ance
compe i ions we e ee o GI complica ions, e en hough immedia ely a e exe cise, hese
le els dec eased signi ican ly. I seems ha p olonged physical e o al e s gu mic obial
ac i i y and unc ional in es inal ac i i y, p esen ing as gu pe meabili y, bu he educ ion
o ood in ake may also be ela ed o gas oin es inal mo ili y and endoc ine me aboli es,
such as lep in, gh elin, and neu o ansmi e s. Nu i ional and p obio ic adminis a ion
p io o maximal physiological e o could be an in e es ing s a egy o minimize he
Mic oo ganisms 2024,12, 1160 8 o 15
possible nega i e e ec s o s imulus such as HA, hypoxia, and/o p olonged maximal
exe cise on gu mic obio a. The adminis a ion o some p obio ics sugges ed in Re s. [
89
,
90
],
as well as o he s, such as Esche ichia coli Nissle 1917 (EcN), has been demons a ed o be
e ec i e in p e en ing he ba ie dis up ion caused by in ec ion o T84 and Caco-2 cells
wi h an en e opa hogenic Esche ichia coli s ain [91].
Ano he p obio ic s ain, Lac obacillus plan a um MB452 ( om he VSL3 p obio ic),
induces he ansc ip ion o genes like occludin and cingulin ha imp o e gu ba ie
in eg i y [
92
]. A s udy has shown ha L. plan a um can egula e human epi helial TJ
p o eins
in i o
and con e p o ec i e e ec s agains chemically induced epi helial ba ie
dis up ion in an
in i o
model [
93
]. Adminis a ion o L. plan a um in he duodenum
o heal hy human olun ee s signi ican ly inc eases zonuline and occludin nea he TJ
s uc u es [
93
]. These indings sugges ha L. plan a um adminis a ion may enhance he
s abili y o TJ complexes in humans and a enua e hei dis up ion by cy okines, oxins, and
pa hogens. Besides L. plan a um, o he Lac obacillus p obio ic s ains also show p o ec i e
e ec s on he in es inal ba ie . Among hese s ains a e L. sali a ius UCC118,L. sali a ius
CCUG38008,L. hamnosus GG, he Lac obacillus casei DN-114.001 s ain, and he Lac obacillus
casei Shi o a s ain [94–98].
Taking ce ain i amins has also p o en o be e ec i e in imp o ing GM balance.
Vi amin A and i s de i a i es ha e been shown o egula e he g ow h and di e en ia ion
o in es inal cells [
99
]. Vi amin D also appea s o play a ole in in es inal ba ie . Vi amin
D de iciency, a cha ac e is ic o in lamma o y bowel disease (IBD), co ela es wi h ce ain
disease se e i y [
100
]. Supplemen a ion wi h asco bic acid can na u ally educe pos -
exe cise LPS concen a ion by ~12 old [101]. Supplemen a ion wi h glu amine in a hle es
wi h inadequa e le els can imp o e in es inal ba ie heal h, as p e iously desc ibed in
esponse o ex eme s esso s, including al i ude shock and hea shock in humans [
102
].
Sho -chain a y acids (SCFA), including bu y a e, play a pa icula ole in main aining he
in es inal ba ie [
103
]. To ele a e SCFA me aboli es, i is impo an include p ebio ics in
he die daily, especially galac ooligosaccha ides (GOS) [
104
] and uc ooligosaccha ides
(FOS) [
105
], as well as esis an s a ch ha eeds SCFA-p oducing bac e ia. Among hese,
bu y a e s ands ou o i s ole in main aining he in es inal ba ie [
103
]. Acco ding o a
s udy using a s wi h coli is induced by dex an sodium sul a e [
106
], he adminis a ion
o bu y a e could be use ul o a eco e y o ansepi helial esis ance associa ed wi h
he main enance o he in eg i y o igh junc ions and he inhibi ion o he elease o
in lamma o y ac o s such as TNFα.
Rega ding supplemen a ion, i is c ucial o me iculously in es iga e he bene i s o i s
use because, as sugges ed Ál a ez-He ms e al. [
30
], a possible associa ion be ween sup-
plemen in ake and de e io a ion o he gu mic obio a (GM) could appea . Supplemen s
and p obio ics include no mal indus ial addi i es ha , in excess, may exace ba e eac i e
in es inal esponses, inc easing gu bac e ial dysbiosis. Food addi i es p esen in unc ional
nu i ional p oduc s, such as p obio ics and/o supplemen s, a e nume ous, including
p ese a i es (sul u dioxide, sodium sul ide and/o benzoa e, e c.), la o enhance s
(monosodium glu ama e), a i icial swee ene s (suc alose, xyli ol, so bi ol, saccha in, e c.),
colo an s ( i anium dioxide), and emulsi ie s [
30
,
107
]. The e o e, i is impo an o con-
sciously e alua e he quali y and quan i y o he supplemen a ion o a hle es, speci ically
conside ing he p ecise nu i ional o a hle es in ega ds o indi idual GM balance.
As can be seen in Figu e 3, di e en s a egies can p omo e GM eubiosis and imp o e
bo h sys emic heal h and physiological pe o mance. Con a ily, he main enance o ch onic
daily habi s ha nega i ely a ec GM homeos asis may exace ba e in lamma o y esponses,
agg a a ing in ole ance o HS and physical exe cise.
Mic oo ganisms 2024,12, 1160 9 o 15
Figu e 3. Hea s ess aining in a hle es can lead o posi i e adap i e physiological esponses
o con as ingly, p omo e abe an physiological consequences. HS can p omo e o agg a a e GM
dysbiosis. A hle es a e equi ed o main ain sys emic heal h o each hei maximal biological po en ial
and acqui e physiological bene i s om he suppo ed s imulus. A hle es wi h poo conside a ion
o hei own heal h a e exposed o GM dysbiosis and ole a e poo maximal physical exe cise and
ano he s imuli, including HS o hypoxia.
App oaches o p ese ing gu heal h and imp o ing he adap a ion o HS s imuli can
ocus on bo h enhancing he consump ion o ce ain oods and subs ances bene icial o gu
eubiosis and a oiding hose ha may dis up gu balance and hea ole ance. In his ega d,
i has been epo ed ha he in ake o ce ain medica ions, such as an icholines e ases,
an idep essan s, diu e ics [
108
,
109
], o non-s e oidal an i-in lamma o y d ugs, can lead
o dis u bances in swea ing, he mo egula ion [
110
], in es inal in lamma ion [
111
], and
can e en ually con ibu e o he exace ba ion o gu dysbiosis and leaky gu synd ome.
Alcohol in ake has also been linked o inc eased in es inal pe meabili y and consequen
endo oxemia [94,112].
4. Gu Heal h as he Key Fac o o Indi idualize S imulus o Physical Exe cise and HA
Be o e ecommending ha a hle es ollow speci ic aining plans, including en i-
onmen al s imulus such as hype he mia and/o hypoxia, i is necessa y o ake in o
conside a ion he GM balance o p omo e posi i e in e en ions. Moni o ing indi idual
p e- and pos -GM changes a e di e en HA in e en ions appea s o be a key s a egy
o enhance he indi idualiza ion o an a hle e’s sys emic heal h and a o g ea e adap -
abili y [
111
]. Di e en ma ke s o de e mine he s a e o he GM and gu pe meabili y
ha e been epo ed, such as (see Figu e 3): (1) le els o sys emic LPS [
22
,
23
,
39
], (2) ci cu-
la ing an ibodies agains he endo oxin co e (EndoCAb) [
113
,
114
], (3) a y acid binding
p o eins (FABPs) [
115
–
117
], (4) ecal calp o ec in [
113
], (5) sec e o y IgA [
115
], and (6) ecal
β-de ensin-2 [117].
In summa y, he e is limi ed e idence ega ding he e ec s ha a heal hy GM can
p oduce on HA ole ance and he consequences associa ed wi h hea eac i e mechanisms.
Ne e heless, i is impe a i e o in es iga e he p ecise mechanisms unde lying unc ional
communica ions be ween he mic obio a and physiological HS esponses o imely adjus
