Gut Microbioma Population: An Indicator Really Sensible to Any Change in Age, Diet, Metabolic ...

12 Pages·2015·1.83 MB·English

Hindawi Publishing Corporation
Mediators of Inflammation
Volume 2014, Article ID 901308, 11 pages
http://dx.doi.org/10.1155/2014/901308
Review Article
Gut Microbioma Population: An Indicator Really Sensible to
Any Change in Age, Diet, Metabolic Syndrome, and Life-Style
NoceAnnalisa,1TarantinoAlessio,1TsagueDjoutsopClaudette,1VasiliErald,2
DeLorenzoAntonino,3andDiDanieleNicola1
1DivisionofHypertensionandNephrology,DepartmentofSystemMedicine,UniversityofRomeTorVergata,
VialeOxford81,00133Rome,Italy
2DepartementofDiagnosticandMolecularImaging,InterventionalRadiologyandRadiationTherapy,
UniversityofRomeTorVergata,VialeOxford81,00133Rome,Italy
3DepartmentofBiomedicineandPrevention,DivisionofClinicalNutritionandNutrigenomic,UniversityofRomeTorVergata,
VialeOxford81,00133Rome,Italy
CorrespondenceshouldbeaddressedtoDiDanieleNicola;[email protected]
Received13December2013;Revised8May2014;Accepted8May2014;Published4June2014
AcademicEditor:RiccardoCalafiore
Copyright©2014NoceAnnalisaetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,
whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
Obesityhasbecomeapandemicthreatinthelatest30years.Thetrendoftheprevalenceofoverweightandobesityhasgotan
overallincreaseineverypartoftheworld,regardlessofethnicity,life-styleandsocialties.Highfoodintake,genetic,andsedentary
havebeenrelatedtoobesity;ithasbeenalsohypothesizedthatgutmicrobiotacouldhaveanimpactonthecomplexmechanism
underlyingtheweightgain.Thisreviewaimstoillustratetheactualliteratureaboutgutmicrobiotaanditsrelationwithobesityand
toanalyzethepossibleimplicationsoffactorssuchasdietandlife-styleontothecompositionofgutmicrobiota,thatcanleadto
overweight/obesitycondition.
1.Introduction (dual-energy X-ray absorptiometry). They identified a new
syndrome, called “normal-weightobese (NWO) syndrome”
1.1. Definition and Epidemiology of Obesity: Global and [4]inwomenwithnormalweightandBMIwhosefatmass
RegionalTrends. Themostwidelyparameterutilizedinorder is>30%oftheirtotalbodyweight.NWOwomenarecharac-
todefineoverweightandobesityisBodyMassIndex(BMI, terizedbyearlyinflammation,relatedtotheirbodyfatmass,
defined as the weight in kilograms divided by the height andtheirplasmaproinflammatorycytokinesconcentrationis
in meters squared) [1]. This method is fast, simple, and significantlyincreasedcomparedtononobesewomen[5].
inexpensiveandisoftenpreferredtomoresophisticatedtools
Due to obesity strict connection to several pathological
duetoitslowercostsandavailability[2].
conditions,likecardiovasculardiseases,highbloodpressure
Actually adult subjects with BMI values between 18.5
[6], type II diabetes [7], and many other chronic noncom-
2
and24.9kg/m areconsiderednormal,subjectswithvalues municablediseases(CNCD),itssurveillancehasbeengreatly
2
between 25 and 29.9kg/m are considered overweight, and improvedinthelatestyears.Infact,ithasbeenestimatedthat
2
thosewithBMIhigherthan30kg/m areconsideredobese, obesitycausesmorethan1milliondeathsand12millionlife-
while adult subjects with BMI values lower than 18.5 are yearsofillhealtheveryyear[8].
consideredunderweight[3]. Severalstudieshaveprovedthatoverweightandobesity
Recently a group of researchers has proposed a new are positively correlated with increased risk of mortality in
anthropometric classification by combining the values of 50-year-oldnonsmokers[9].Arelevanthigherprevalencein
BMI and fat mass percentage (FM%), obtained by DEXA malesubjectswasalsoobserved.
2 MediatorsofInflammation
Prevalence of obesity (%)
<10 >30
10–19.9 Data not available
20–29.9 Not applicable
Figure1:WorldwideOverallpercentageofobesityprevalence(2008).Datasource:WHO[1].
Furthermore,inthelatest20–30yearsanincreasedglobal 40
prevalenceofobesityhasbeendetectedinalmosteverypart
35
oftheworld(Figure1).
EspeciallyinUSA,theobesityprevalencehasgreatlyrisen
30
since1980,when15%ofpeoplewereobese;inabout25years
prevalence has reached 34% [12]. In 2006 a study on US 25
childrenagedfrom2to19yearsshowedthat31.9%ofthem
wereatorabovethe85thpercentileofthe2000CDCBMI- 20
for-age growth charts, and 16.3% were at or above the 95th
15
percentileofBMIforage.Consideringthatin1980children
who were at or above 85th percentile were 5.5%, this study
10
reveals a huge increase in US obesity and overweight rates,
thoughsince2006norelevantfurtherincreaseoftheBMI- 5
statedobesityhasbeenobserved[12](Figure2).
Several European studies showed similar data. Despite 0
1980 2008
the remarkable differences in life style, an overall increased
prevalenceofoverweightandobesityhasbeendetected,even
Adult obesity (%)
in nations with a well-known low prevalence of high BMI
Adult overweight (%)
values(mainlyallthesouthernEuropeanstates)[13].
Children obesity (%)
A group of researchers studied the obesity/overweight Children overweight obesity (%)
trend in Italy in the 1983–2010 period, finding an overall
Figure 2: Prevalence’s trend of overweight and obesity in USA
steady increase of prevalence of both conditions until 1997,
population(1980–2008)[1].
with a substantial stabilization of the values since then
(Figure3)[14–17].
In particular, an overall increased prevalence of high
in Brazil-Russia-India-China (BRIC) [22] and developing
BMI values has been observed in the richest countries,
countries,confirmingtheglobalincreasingtrend.
but the higher values have been recorded among the most
disadvantagedsocialclasses[18].Althougheveninthosesub-
groups data showed significant differences between various 1.2. Obesity Etiopathogenesis. A well-defined etiopathogen-
ethnic groups, a high prevalence of overweight/obesity has esis is still far to be recognized; however, actually obesity
beenrecordedinallthegroups,underliningtheimportance is considered a complex, multifactorial condition resulting
of some life-style factors (e.g., unhealthy dietary patterns, from the interaction between the environment, genetic and
reduced physical activity, and the improved of motorized life-stylefactors[23].
transports)[19,20]. Recent studies, however, showed a strongly genetic fea-
Some studies evidenced also a significant role for par- tureintheriskofbecomingobese,inparticularthehomozy-
ent’s educational level, especially mothers [21]. In the latest gotes for mutation in human leptin receptor gene. In fact,
decadesobesityandoverweighthavebecomeepidemiceven theleptinreceptorpolymorphismhasbeenestablishedtobe
MediatorsofInflammation 3
Trend of obesity/overweight in Italy (1983–2010) ofmicrovasculature.Consequentlythe immunecellswould
40
reachtheintestinalepitheliumwheretheyrecognizebacterial
35
antigensandestablishanimmunetolerancerequiredtoavoid
30
%) achronicinflammatorystate[36,37].
25
n ( Inthehumanbody,thegutisthemostdenselycolonized
o 20
ati microbialcommunityandconsistsofnumerousspecies[38,
pul 15 39].Intoitlivetrillionsofmicrobes,composedapproximately
Po 10 by100differentkindsofbacteria,inanumberof1010to1011
5 bacteriapergram.Themajorityofmicrobiotaiscomposedby
0 strictlyanaerobes,eveniffacultativeanaerobesandaerobes
1983 1994 1997 2004 2010
are also present [40]. Although a huge number of different
Year bacteria phyla have been identified, the overall bacterial
population of human gut is determined basically by only
Overweight
2 of them: Bacteroidetes and the Firmicutes, even if Pro-
Obesity
teobacteria, Verrucomicrobia, Actinobacteria, Fusobacteria,
Figure 3: Trend of overweight and obesity in Italian population andCyanobacteriaarealsopresenteveniftheirroleisunclear
(1983–2010)[10,11]. yet.
At present little is known about the development of
the microbiota, even if it has been demonstrated that the
associatedwithobesity,especiallyinCaucasianpopulations microbiotastartsintheearlylifetocolonizehumangut;this
[24].Alsothediscoveryofthefatmassandobesity-associated acknowledgement was acquired due to the observation of
protein(FTO)geneshowedthegeneticroleinthedevelop- the similarities between the intestinal microbiota of infants
mentofobesityandmetabolicsyndrome(MetS)[25]. and the vaginal microbiota of their mothers [41]. It was
Diet is also very important nowadays, because of the also recently stated that the composition of microbiota
diffusionoffoodwithhigh percentage ofcarbohydrate and can be really variable even between people of the same
highlyrefinedoilscausinganexcess ofenergyintakeanda ethnicity, nation, and life-style [42]. It has been specu-
relevantchangeofthemostcommondietary-patterns[20]. lated that the composition of gut microbiota comes from
a complex interaction between several factors like dietary-
pattern, ethnicity, genetic factors, and more. Some reports
2.TheHumanGutMicrobiota
on twins also demonstrated that incidental environmental
exposures play a major role in determining the distinctive
2.1. Definition. In recent years there has been a growing
characteristicsofthemicrobialcommunity,becausedespite
interest for the fact that humans are supraorganisms com-
considerabletemporalvariation,thedistinctfeaturesofeach
posed also by microbial cells [26]. Therefore, the humans
baby’smicrobialcommunitywererecognizableforintervals
carrytwosetsofgenes,thoseencodedontheirowngenome
ofweekstomonths[43].
andthoseencodedinmicrobiotagenome(microbioma).The
The gut functions as a chemostat, a continuous culture
humancellsgenesareabout23,000[27]andmicrobiotagenes
system for microorganisms leave at a relative constant rate
are about 3 million [28, 29]. Thus as superorganism, the
[44].Approximately1.5kgofbacteriaisresidentinhumans
humansinheritonly1%oftheirgenesfromtheirparents,and
gut[33],and50%ofhumanfaecalmatterisbacterialcells.To
the remaining 99% is mainly acquired from the immediate
maintainsuchahighpopulationdensity,thesebacterianeed
environmentwhentheyareborn,andinparticularfromtheir
alotofnutrients,whichcancomefromfoodsourcessuchas
mothers’birthcanalandbreastmilk[30,31].Importantly,all
dietary fibres (which are otherwise indigestible to humans)
thegenesinbody,whetherhumanormicrobiomeencoded,
[45,46],frommucinandfromcellssloughedfromthegut,
havethepotentialtohaveanimpactonhealthstatus[32,33].
aswellasdrugsandotherxenobioticcompounds[47,48].
Theintestinalmicrobiotaisconsideredasasymbiontthat
The host physiologic digestion (characterized by the
ispartoforganismsinceatbirththateducatestheimmune
pH of the gut and by the presence of bile acids) [49, 50]
systemandcontributestothedevelopmentoftheintestinal
and the components of the innate immune response (such
vasculatureandmostprobablyofthenervoussystem(having
as defensins and immunoglobulin A), impose a selective
apositiveimpactoncognition,memory,andothercerebral
pressuretodeterminethemembershipofthegutmicrobiota
skills)[34].
[51].
Astudyofgermfreemice(miceraisedwithoutexposure
toanyorganism[GF])hadshownthatthecolonizationwith However, the microbiota composition is the result of
microbiotapromotesvesseldensityinthesmallintestine[35]. theequilibriumbetweentheabilitytotakeadvantageofthe
Themechanismsthatexplainthisprocessisthepromotionof available nutrients and to withstand the forces removing it
tissue factor (TF) glycosylation associated with its localiza- fromthegut[52].
tionatthecellsurface,theactivationofcoagulationproteases, Recentstudiesdemonstratedthatageingalsohasamajor
and the phosphorylation of the TF cytoplasmic domain role in the transformation of microbiota; in fact the com-
in the small intestine. This mechanism could favour the position of microbial flora can be totally different between
developmentoftheimmunesystemcausingthematuration children, adults, and elderly. Microbioma can also change
4 MediatorsofInflammation
forpathologicalconditions(like chronicinflammatoryguts 2.3. The Mechanisms Underlying Weight Gain. Due to the
diseasesandmetabolicdiseasesuchastypeIIdiabetes)[53, increase of the overweight status in the latest decades, the
54]. attentionontheobesityconditionincreasedinalmostevery
field of research; obviously, also human gut and human
gutmicrobiotawereinvolved.Themutualisticnatureofthe
2.2.MicrobiotaandMetabolism. Gutmicrobiotaplaysakey
host-bacterial relationship is underscored by mechanisms
role in human metabolism; in fact, up to one-third of the
thatunderliefat-storagephenotype.Ourmicrobialpartners
small molecules in human blood can be derived from gut
have coevolved with us forging a symbiotic relationship,
bacteria[55–57].
with mutual advantage. This relationship is established on
Metabolitesproducedbygutbacteriacanentertheblood-
nutrientsharing.Ba¨ckhedetal.[80]statedintheirstudythat
stream by absorption, by enterohepatic circulation, or by
onemanifestationofthissymbioticrelationshipismicrobial
impairedgutbarrierfunction[58].Somemicrobiota-derived
processingofcomponentsofthefoodintakeanddeposition
metabolitescanhaveapositiveimpactonthehost,including
the extracted energy in host fat depots. The ability to store
thosewithanti-inflammatory[59],antioxidant[60],orpain
energy was essential for ancient humans who did not have
reliefactivity[61],andthosethatregulategutbarrierfunction easyaccesstofood.However,nowadays,becauseofthewide-
[62] as well as those acting as vitamins [63] or energy spreading of large-portion, high-calorie diets, this “benefit”
sources [64]. For example, butyrate, which is produced by becameadetriment.
bacterial fermentationof dietary fibres, can serve as energy Microbiotacolonizationincreasesglucose uptakein the
source for colonocytes and can increase satiety [65, 66]. host intestine and induces a substantial elevation in serum
Thiscompoundisalsoeffectiveinalleviatinginflammation, glucose and insulin, both of which stimulate hepatic lipo-
reducingcarcinogenesis,andmitigatingoxidativestress[62, genesis through their activity on two transcription factors
67]. (ChREBPandSREBP-1c)[81].
By contrast, other microbiota-derived metabolites are Short-chain fatty acids, generated by microbial fermen-
toxictotheirhost,includingcytotoxins[68],genotoxins[69], tation,alsoinducelipogenesis.Triglyceridesexportedbythe
and immunotoxins [70]. For example, lipopolysaccharide liverintothecirculationaretakenupbyadipocytesthrough
(LPS), an endotoxin released by gram-negative bacteria, alipoproteinlipase-(LPL-)mediatedprocess.
can provoke an inflammatory response and thus aggravate Themicrobiotasuppressesintestinalepithelialexpression
inflammation-related chronic conditions such as insulin ofacirculatingLPLinhibitorcalledfasting-inducedadipose
resistance[62,70,71]. factor(Fiaf).ComparisonsofGF,conventionalizedwild-type
Thecausalroleofgutmicrobiotainthecontrolofenergy andmiceknocked-outfortheFiafgene,establishedthatFiaf
homeostasis was first demonstrated by comparative study isaphysiologicallyimportantregulatorofLPLactivityinvivo
betweenconventional(CV)miceandgermfree(GF)micefed andakeymodulatorofthemicrobiota-inducedincreaseinfat
withhigh-fat(HF)diet[72].Whereasconventionalmicegain storage.However,itisreasonabletopostulatethatthecaloric
weightasexpected,theGFmiceremainedleanalthoughtheir value varies between individuals due to their different gut
dailyamountoffoodintakewasdramaticallyincreased[72], microbiotacomposition,differentintestinaltransittime,and
suggestinganimpairedfeedingefficiency.Bodyweightgain thefactthatthemicrobiotainfluenceshumanenergybalance.
wasgreaterwhenthegermfreemicewerecolonizedwiththe The humans are divided into the following: “high effi-
microbiotafromobeseratherthanfromaleanmouse[73]. ciencybioreactors”and“lowefficiencybioreactors,”accord-
Furtherstudiesdemonstratedthatthehigh-fatdietresponse ing to the ability to harvest energy from feeding and to
is not only dependent on GF state but also dependent on promotestorage.Relativelythefirstareinvolvedintodevel-
type of HF-diet; it was stated that a diet with high content opment of obesity while the last are significantly related to
ofsucrosehadagreaterlipogeniceffectonCVmicethanon leanness.
GFmice[74,75]. The idea that individual variations in bioreactor effi-
It was subsequently shown that obese patients were ciencies may be a significant variable in the energy bal-
characterized by an intestinal microbiota dysbiosis where ance equation is supported by several observations. First,
the proportion of the principal phyla (Firmicutes and Bac- individual variations in the composition of the microbiota
teroidetes)waschangedinfavourofanexcessofFirmicutes occurandareinfluencedbyhostgenotype.Second,smallbut
when compared with lean controls [76]. This dysbiosis was chronic differences between energy intake and expenditure
reversed when the obese patients were submitted to caloric canproducemajorchangesinbodycomposition.Third,the
restrictions for several months. Interestingly, the obese microbiotaisasubstantialconsumerofenergy[81].
leptin-deprived ob/ob mice showed similar intestinal dys- A recent study demonstrated that individuals on a
biosis[77]suggestingacommonmechanismbetweenmice “Britishdiet”mustferment50to65gofhexosesugarsdaily
andhumans. to obtain the energy required to replace the 15 to 20g of
Butothersstudiescontradictwiththesepreviousreports bacteriatheyexcreteperday.Inmicrobiota,therearespecies
with regard to the contribution of various bacterial micro- withlargercapacitiesforprocessingdietarypolysaccharides,
biota composition to the development of obesity; in par- such as Bacteroides, and they are more represented in lean
ticular,theBacteroides/Firmicutesratiohasbeenprovedas subjects than in morbidly obese subjects. So, differences
insignificant[78,79]. in the composition of the microbiota are associated with
MediatorsofInflammation 5
differencesingutbioreactorefficiencyandpredispositionof the peroxisomal proliferator activated receptor coactivator
obesity[80]. (Pgc-1) and enzymes involved in fatty acid oxidation. Thus,
As we adapt to changes of the environment, the gut GF animalsareprotectedfromdiet inducedobesityby two
microbiotaadaptstoqualitativeandquantitativechangesof complementary but independent mechanisms that result in
ourdiet.Particularly,bacteriaofthelargeintestinerespond increasedfattyacidmetabolism[87–89].
to changes in diet, especially to the type and quantity of Thegutmicrobiotawasalsostudiedinordertoassessa
dietary carbohydrate. One of the main consequences of possiblecorrelationwithotherchronicdegenerativediseases
increasedcarbohydrateintakeistodecreasethepHofthegut likechronicinflammation,insulinresistance,type2diabetes
lumen,significantlyalteringbacterialmetabolismandcom- mellitus, and atherosclerosis. Cani and Delzenne studied
mensalprevalence.Thesurplusofcarbohydratesbreakdown mice after a period of 2–4 weeks of high-fat diet for the
is channeled by components of the microbiota into energy purpose of finding any important relation between food
storage.Infact,certaincommensalspeciessuchasFirmicutes intake,microbiotacompositionanddevelopmentofobesity,
suppresscirculatingLPLinhibitors,thusinducingincreased and metabolic syndrome [90]. They found out a significant
enzymeactivityandenergyaccumulationasfat[82–85]. increaseinplasmaLPSandnamedthiscondition“metabolic
endotoxemia,” because levels of circulating LPS were lower
thanthoserelevatedduringacanonicsepticshock[91].
2.4. In Vitro/Animal Studies. A team lead by JI Gordon has
studiedtheimportanceofgutmicrobiotaasanenvironmen- FurthermoreitwasobservedthathighLPSlevelscoming
talfactorregulatingfatstorageandplayingaroleinobesity.In from a high-fat diet can be absorbed by gut epithelium
fact,thecolonizationofgerm-freemicebymousemicrobiota inducing a low-grade inflammation that is strictly involved
producesamassiveincreaseinbodyfat(+60%)andinsulin inthedevelopmentofobesity.Inthisinflammatoryprocess
resistance. The association of Bacteroides thetaiotaomicron there is a reduction of the Bacteroides number and an
and Methanobrevibacter smithii increased the metabolic increaseofFirmicutes,atypicalconditionobservedinobese
activityofgerm-freecolonizedmice.Weightandfatincreases subject[90].
in mice were not related to food consumption increase
but, rather, to food conversion ratio increase (increase of 2.5. In Vivo Studies. A remarkable number of researchers
weight/ingested food weight). When comparing offspring studied different populations (children, adult, elderly, lean,
andmothermicrobiotainnongeneticallyobesemice,itwas overweight, and obese), different even for ethnicity and
found that the offspring’s microbiota reflected that of the social-economic conditions. The results obtained have
mother[73]. demonstrated a dominant role of environment and others
Microbiota transplantation from either lean or obese life-style related factors [92], although alterations in the
miceintothegutofgerm-freemiceresultedin,respectively, human intestinal microbiota are also linked to pathologic
lessormorebodyfat,evenwhenthecaloricintakeremained conditionssuchasinflammatoryboweldiseaseandirritable
the same. Genetic and environmental factors influenced bowelsyndrome[93].
microbiotacompositioninmice.Microbiotaislinkedtoobe- Muelleretal.haveshowedthatawell-definedmicrobiota
sityeitherasacause(transferofmicrobiota)oraconsequence population for any studied subgroup (such as age, socio-
(obesegenotype)[73]. economiccondition,life-style)cannotbeidentified[94].
Raoult recently found that a single adsorption of a Thewaysinwhichthegutsmicrobepopulationinfluences
Lactobacillus strain dramatically increased food conversion obesity is not yet well-know; it was hypothesized that this
andweightincreaseinchickens.Takentogether,theempirical can happen by several mechanisms, like increasing dietary
data from agriculture and experimental data in laboratory energyharvest,promotingfatdeposition,triggeringsystemic
animalsshowedthatmanipulatinggutmicrobiotabyantibi- inflammation, perhaps modifying locomotor activity, and
otic ingestion or by contamination with selected bacteria havingcentraleffectsonsatiety[95].
causes a significant weight gain. It is difficult to reject the
DiBaise and his group tried to find out a connection
hypothesisthatantibioticsandprobioticsmayhavethesame
betweenobesityandgutmicrobiotasuggestingthatbacterial
effectinhumans[86].
lipopolysaccharide derived from the intestinal microbiota
Ba¨ckhedetal.reportthat,incontrasttomicewithagut
mayactasatriggeringfactorlinkinginflammationtohigh-
microbiota,thegerm-free(GF)miceareprotectedagainstthe
fatdiet-inducedmetabolicsyndrome[96].
obesitythatdevelopsafterconsumingahigh-fatandsugar-
Ithasbeensuggestedalsothatantibioticsandprobiotics
rich diet. Their persistently lean phenotype is associated
maybeabletoinfluencetheBMIandweightgainduetotheir
with increased skeletal muscle and liver levels of phos-
effectsonmicrobiotapopulation,causinganincreaseonfat
phorylated AMP-activated protein kinase (AMPK) and its
downstreamtargetsinvolvedinfattyacidoxidation(acetyl- andweightgainevenwithoutgeneticallypredisposingfactors
CoAcarboxylase;carnitinepalmitoyltransferase).Moreover, orincreasedfoodintake[86].
GF knockout mice lacking fasting-induced adipose factor
(Fiaf)arenotprotectedfromdiet-inducedobesity.Although 2.5.1. In Elderly Subjects. In old age there is a progressive
GF Fiaf−/− animals exhibit similar levels of phosphory- changeinbacteriapopulation.Medicaltreatment,inparticu-
lated AMPK as wild-type mice in liver and gastrocnemius larantibiotics,affectscompetitivenessandcolonizationresis-
muscle, they have reduced expression of genes encoding tance.Furthermore,hostphysiologymaybecompromisedin
6 MediatorsofInflammation
agedpopulationsowingtoareducedtasteandsmellpercep- overweight women and 36 normal-weight women (control
tion. For example, achlorhydria, which is often observed in group).Theyobservedthatmicrobialcountsincreasedfrom
elderlysubjects,mayresultinreducedcolonizationresistance thefirsttothirdtrimesterofpregnancyandhighBacteroides
and lead to bacterial overgrowth of the stomach and the concentrations were associated with excessive weight gain
small intestine. In addition, elderly tends to deviate from over pregnancy. In addition, the differences in Bifidobac-
usual dietary habits, which in turn may influence bacterial teriumgenusnumbersbetweenthefirstandthirdtrimesters
colonization[97,98]. ofpregnancyshowedacorrelationwithnormalweightgain
The microbiota also undergoes substantial changes at overpregnancy,suggestingthatBifidobacteriumcountswere
the extremes of life, in infants and older people. The core higher in women with lower weight gain over pregnancy
microbiota of elderly subjects was distinct from that pre- [104].
viously established for younger adults, with a greater pro- A recent study reports that high-fat feeding is associ-
portionofBacteroidesspp.anddistinctabundancepatterns atedwithlowerconcentrationsofbifidobacteria[105].High
of Clostridium groups. The fecal microbiota of the elderly numbers of bifidobacteria may correlate positively with the
showstemporalstabilityoverlimitedtimeinthemajorityof normalizationofinflammatorystatusandimprovedglucose
subjectsbutischaracterizedbyunusualphylumproportions toleranceandglucose-inducedinsulinsecretion.Then,alow
andextremevariability[99]. number of Bifidobacterium in overweight mothers may be
associatedwithinflammatoryprocesses.Bifidobacteriumhas
In elderly persons bifidobacteria decrease or disappear,
thusanimportanteffectonmicrobiotatransferfrommothers
clostridia including C. perfringens significantly increase,
to infants. It may be important to modify the microbiota
and lactobacilli, streptococci, and enterobacteriaceae also
of pregnant women to influence the first inoculum and the
increase.
transfer of microbiota to the infant, because it may have a
TomotariMitsuokaretainedthattheabnormalfloraare
significanteffectonthelaterhealthoftheinfant[104].
generallycharacterizedbyaremarkableincreaseinbacterial
Patiletal.reportacomparativeandquantitativeanalysis
countsinthesmallintestine,byanincreaseofaerobes,mostly
of dominant gut microbiota of lean, normal-weight, obese,
enterobacteriaceaeandstreptococci,bythereductionordis-
and surgically treated obese individuals of Indian origin.
appearance of bifidobacteria, and/or often by the incidence
They observed that the bacteria of genus Bacteroides were
of C. perfringens. This ecological evidence would suggest
prominent among the obese individuals. In addition, a
that bifidobacteria should exist in the large intestine for
remarkably high archaeal density was also noted in the
maintenanceofhealthstatusandarefarmoreimportantthan
obese group. On the contrary, the surgically treated obese
lactobacilli as the beneficial intestinal bacteria throughout
individualsexhibitedcomparativelyreducedBacteroidesand
human life. In other words, the reduction or disappearance
archaealcounts[106].
of bifidobacteria in the human intestine would indicate an
“unhealthy”state[100–102]. Fernandez-Raudales et al. compare, in a randomized
double-blind study, the effects of consuming low glycinin
soymilk(LGS),conventionalsoymilk(S),orbovinemilk(M)
2.5.2. Adult Subjects. Turnbaugh et al. studied adult female
ontheintestinalmicrobiomeinoverweightandobesemen.
monozygotic and dizygotic twin pairs concordant for lean-
Theparticipantsweredividedinthreesubgroups:consumed
ness or obesity in order to assess the existence of a “core”
500mL daily of LGS, S, or M for 3 months. PCR analysis
humangutmicrobiome.Innoneofthe154enrolledsubjects
showedthatthetotalbacteriaincreasedinalltreatmentsover
was detectable a single bacterial phylotype by a set of
time. Bacteroides-Prevotella and Lactobacillus increased in
abundant microbial lineages that we all share, proving that
LGS and M, respectively. Bifidobacterium was significantly
thishypothesisiswrong;hovewer,theauthorsfoundoutan
reducedinLGS.BacterialdiversitydecreasedforLGS,S,and
importantconnectioninsharedgenes.Thisdiscoverygained
M. Then, the consumption of the three beverages differen-
majorrelevancewhenresearchersassessedthatthosegenes
tially altered the microbiota in overweight and obese men
were greatly involved in a lot of very important metabolic
includingapotentiallybeneficialalterationoftheFirmicutes
functions.Theauthorscomparedthissituationtoanisland,
toBacteroidetesratioinbothsoymilkgroups[107].
assesting that every person is an island with a unique gut
microbioma,inwhichdifferentspeciesassemblagesconverge
onsharedcorefunctionsprovidedbydistinctivecomponents 2.5.3. In Babies and Young Subjects. By one year of age, the
[103]. babiesretainedtheiruniquenessbuttheyconvergedtoward
Collado et al. hypothesized that the gut microbiota aprofilecharacteristicoftheadultgastrointestinaltract[43].
compositiondiffersinobesepregnantwomencomparedwith Timsetal.demonstratedthatmonozygotictwinshavea
normal-weight pregnant women and it may be associated more similar microbiota compared with unrelated subjects;
with weight gain during pregnancy. The deviations in gut the composition and temporal patterns of development of
microbiotacompositionduringpregnancycouldpredispose the intestinal microbiota in a pair of fraternal twins were
toexcessiveenergystorageresultinginhigherbirthweight. strikinglysimilar,suggestingthatgeneticandenvironmental
Thisisaviciouscirclebecauseoverweightinfantsfrequently factorsshapeourgutmicrobiotainareproducibleway.
becomeoverweightadolescentsandobeseadultswithahigh Then, lower BMI was associated with a more abundant
risk of Western life-style diseases. These researches lead a network of primary fiber degraders, while a network of
comparativestudyontoapopulationofpregnantwomen:18 butyrate producers was more prominent in subjects with
MediatorsofInflammation 7
higherBMI.InthehigherBMIsubjectsbutyrateandvalerate Further studies should investigate the possibility to
contentsinthefecalmatterwereincreased.Thesedifferences improvegutshealthstatusbypreventinggutsdysbiosisand
inmicrobialnetworkssuggestashiftinfermentationpatterns characterize the weight gain process. Actually the results of
at the end of the colon, which could affect human energy severaltrialshavebeeninconsistentwithregardtothetype
homeostasis[108]. of probiotic used, dosing and timing of agent selected, and
De Filippo et al. has examined two children population thepopulationlikelytobenefit.
one coming from Europe and the other from rural Africa
in a comparative study. Both in the Western world and AbbreviationList
in the developing countries diets rich in fat, protein, and
sugar, together with reduced intake of unabsorbable fibers, AMPC: Cyclicadenosinemonophosphate
are associated with a rapid increase in the incidence of BMI: BodyMassIndex
noninfectious intestinal diseases. The potential protective BRIC: Brazil-Russia-India-China
effects of the diet on bowel disorders were first described CNCD: Chronicnoncommunicablediseases
by Burkitt who, working in Africa in the 1960s, noticed ChrEBP: Carbohydrate-responsiveelement-binding
theremarkableabsenceofnoninfectiouscolonicdiseasesin protein
Africansconsumingatraditionaldietrichinfiber[109]. CKD: Chronickidneydisease
DEXA: Dual-energyX-rayabsorptiometry
Vaeletal.evaluatetheintestinalfloraininfantsrecruited
Fiaf: Fasting-inducedadiposefactor
prospectively from the general population at birth and
FM%: Fatmasspercentage
followeduptotheageof3years.HighintestinalBacteroides
FTO: Fatmassandobesityassociatedgene
fragilis and low Staphylococcus concentrations in infants
GF: Germ-free
between3weeksfrombirthand1yearwereassociatedwitha
LGS: Lowglycininsoymilk
higherriskofobesitylaterinlife.Thisstudysuggeststhatearly
LPL: Lipoproteinlipase
differences in the composition of the intestinal microflora
NWO: Normalweightobese
precedethedevelopmentofobesityinchildren.
PGC-1: Peroxisomalproliferatoractivated
Modificationoftheintestinalmicrofloraininfantsmight
receptorcoactivator
represent a new strategy for prevention and treatment of
SREBP-1C: Sterolregulatoryelement-bindingprotein
obesity[110].
1c.
Bervoetsetal.[111]focusedonthepositiveroleofbifido-
bacteria[112,113]andstudiedthecompositionofgutmicro-
ConflictofInterests
biota in obese and lean children. This study considered a
populationof26obese/overweightsubjects(BMI28.7±6.5) The authors declare that there is no conflict of interests
and27leansubjects,inordertocalculatetheconcentration regardingthepublicationofthispaper.
of bacterial species mostly related with major digestive
process(inparticular:Bacteroides,Bifidobacterium,Clostrid-
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