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The Use of Defined Microbial Communities To ModelHost-Microbe Interactions in the Human Gut

Janneke Elzinga,a John van der Oost,a Willem M. de Vos,a,b Hauke Smidta

aLaboratory of Microbiology, Wageningen University and Research, Wageningen, The NetherlandsbResearch Programme Unit Human Microbiome, Faculty of Medicine, Helsinki University, Helsinki, Finland

SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2DEFINED COMMUNITIES MIMICKING THE NORMAL INTESTINAL MICROBIOTA

IN VIVO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3(Altered) Schaedler Flora . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3Oligo-MM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20SIHUMI(x) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20Toward a Normal Model Gut Microbiota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21Defined Communities in Nonrodents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

OTHER DEFINED COMMUNITIES IN VIVO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Therapeutic Communities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23Minimal Communities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24

CRITICAL EVALUATION OF DEFINED COMMUNITIES IN VIVO: THE MICROBIOTA . . . . . 24How Representative Are Defined Microbiota Models of a Normal Microbiota? . . . . . . . . . 24Simplified versus Complex Communities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25Bottom-Up versus Top-Down Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27Future Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27

CRITICAL EVALUATION OF DEFINED COMMUNITIES IN VIVO: THE HOST . . . . . . . . . . . . . . 28Host Parameters Influencing the Microbiota . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28Validation of In Vivo Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

DEFINED COMMUNITIES IN VITRO . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31Modeling the Intestinal Microbiota In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31Modeling the Host In Vitro . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32Validation of In Vitro Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

CONCLUSIONS AND FUTURE OUTLOOK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33ACKNOWLEDGMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34AUTHOR BIOS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

SUMMARY The human intestinal ecosystem is characterized by a complex interplaybetween different microorganisms and the host. The high variation within the hu-man population further complicates the quest toward an adequate understanding ofthis complex system that is so relevant to human health and well-being. To studyhost-microbe interactions, defined synthetic bacterial communities have been intro-duced in gnotobiotic animals or in sophisticated in vitro cell models. This review re-inforces that our limited understanding has often hampered the appropriate designof defined communities that represent the human gut microbiota. On top of this,some communities have been applied to in vivo models that differ appreciably fromthe human host. In this review, the advantages and disadvantages of using definedmicrobial communities are outlined, and suggestions for future improvement ofhost-microbe interaction models are provided. With respect to the host, technologi-cal advances, such as the development of a gut-on-a-chip system and intestinal or-ganoids, may contribute to more-accurate in vitro models of the human host. Withrespect to the microbiota, due to the increasing availability of representative cul-tured isolates and their genomic sequences, our understanding and controllability of

Citation Elzinga J, van der Oost J, de Vos WM,Smidt H. 2019. The use of defined microbialcommunities to model host-microbeinteractions in the human gut. Microbiol MolBiol Rev 83:e00054-18. https://doi.org/10.1128/MMBR.00054-18.

Copyright © 2019 American Society forMicrobiology. All Rights Reserved.

Address correspondence to Janneke Elzinga,[email protected].

Published 13 March 2019

REVIEW

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the human gut “core microbiota” are likely to increase. Taken together, these ad-vancements could further unravel the molecular mechanisms underlying the humangut microbiota superorganism. Such a gain of insight would provide a solid basis forthe improvement of pre-, pro-, and synbiotics as well as the development of newtherapeutic microbes.

KEYWORDS animal model, gut-on-a-chip, in vitro model, intestinal microbiota,minimal microbiota

INTRODUCTION

Given its involvement in metabolic, nutritional, physiological, and immunologicalprocesses, the human intestinal microbiome can be regarded as an essential organof the human body (1). Further strengthening its clinical relevance, the intestinalmicrobiome has been linked to numerous disease conditions, including metabolic andimmune disorders, cancer, and neurodegenerative diseases (2). However, apart from aremarkable increase in the amount of genome sequence data of the human gutmicrobiota, progress in functional insight has been hampered by its complexity: theexistence of more than 1,000 prevalent species (3), combined with the high interper-sonal variation within the human population in terms of genetics, environment, andhabits, results in a complex entity termed the human microbiome superorganism (4).The number of known host-microbe interactions has grown rapidly over the pastdecades, yet many aspects still remain obscure.

To solve this complexity, there is a need for a reductionist approach in which bothhost and microbiome are simplified to the extent that experimental variables can betightly controlled and deliberately manipulated. Regarding the microbiota, synthetic ordefined communities have been proposed as useful models to study microbial ecology(5). In recent years, the number of cultivable gastrointestinal microbial species hasrapidly expanded (3) by the use of sophisticated or brute-force culturomics approaches(6, 7). These strategies have allowed for the design of defined communities that arerepresentative of the normal human intestinal microbiota. With respect to the humanhost, laboratory animals, notably mice, have proven valuable models for developinghuman medicine. The colonization of germfree (GF) animals with defined bacterialcommunities, resulting in gnotobiotic animals, has already been applied for decades.During the 1960s and 1970s, it was recognized that the intestines of GF animals displayaberrant histological, anatomical, and physiological characteristics compared to con-ventional laboratory animals (8). The development of the Schaedler cocktail for colo-nization of the murine gut (9) marked one of the first attempts to normalize GF mice.An altered version has been widely adopted as a standardized gut microbiota by animalbreeders and biomedical researchers ever since. Over time, various other definedcommunities have been designed to generate gnotobiotic animals for purposes be-yond standardization; they have proven to be a valuable in vivo tool to study microbialecology (e.g., microbial invasion, microbe-microbe interactions, and metabolism) andhost-microbe interactions. However, mice and other animal models have variouslimitations that hamper their use as models for the human microbiome, as was recentlyreviewed (10, 11). Interesting alternatives concern the development of sophisticated invitro models, such as organ-on-a-chip systems and organoids.

This review summarizes existing models of host-microbe interactions in whichdefined communities, as models of the (human) gut microbiota, were applied. We aimto present all in vivo studies that used defined microbial communities representing theintestinal microbiota of healthy individuals and in which host parameters were con-sidered. The designs of these model communities, as well as the selection of their host,are compared and critically evaluated. The potential uses of defined communities in invitro (cellular) models, as a surrogate host, are outlined as well. We conclude bydiscussing the increased value, opportunities, and possible obstacles when applyingdefined communities in to-be-developed in vitro host-microbe interaction models.

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DEFINED COMMUNITIES MIMICKING THE NORMAL INTESTINAL MICROBIOTAIN VIVO

A number of recent studies addressed host-microbe interactions in vivo by usingdefined communities representative of the healthy human gut microbiota (Tables 1 to 3).These include various mouse studies with more- or less-defined intestinal microbiota,which are summarized below. Studies in which animals were antibiotic treated beforebacterial colonization are excluded from our analysis, as their reproducibility andgnotobiology cannot be ensured (12). The following section first discusses the specif-ically named defined communities applied in rodents (Table 1) (n � 31), followed bynon-specifically-named communities in rodents (Table 2) (n � 16). Finally, the definedcommunities administered to nonrodent models are discussed (Table 3) (n � 6).

(Altered) Schaedler Flora

In 1965, Russel W. Schaedler colonized GF mice with a defined microbial communitycomposed of strains isolated from normal mice, to study the fate of the bacteria in thegastrointestinal tract (GIT) and their effect on cecum size. With respect to theseparameters, it turned out that the Schaedler flora (SF) was able to, at least partially,normalize the cecum size of GF mice in comparison with animals raised under con-ventional conditions (9). The defined microbial population was supplied to animalvendors to serve as a community that could limit infection of ex-GF rodents withopportunistic pathogens. Schaedler developed several different bacterial cocktails overtime. In 1978, Roger P. Orcutt set out to standardize and improve the SF flora, but inview of the monitoring costs, the total number of bacterial species was limited to eight.Orcutt made a selection of bacterial species (altered Schaedler flora [ASF]) based ontheir representation and stable colonization in the murine gut, their ease of identifi-cation (morphologically), and their presence in or interference with isolator contami-nants. For instance, the cocci and spore-forming, blunt-ended rods were eliminated,which represented the majority of isolator contaminants. Also, the amount of faculta-tive anaerobes was limited, as they outgrew aerobic isolator contaminants and thusimpeded the ability to detect the latter (13). The ASF consists of six Firmicutes (Clos-tridium species [ASF356], Lactobacillus intestinalis or Lactobacillus acidophilus [ASF360],Lactobacillus murinus or Lactobacillus salivarius [ASF361], Eubacterium plexicaudatum[ASF492], Pseudoflavonifractor sp. [ASF500], and Clostridium sp. [ASF502]), one Bacte-roidetes species (Parabacteroides distasonis [ASF519]), and one Deferribacteres species(Mucispirillum schaedleri [ASF457]).

The ASF has been used multiple times as a reference or minimal defined microbiota,and its applications were extensively reviewed elsewhere (14). Several studies involvingASF in mice (or other animals) reported its effect on host parameters (Tables 1 to 3). Thelist is probably not exhaustive, given the wide application of ASF mice as a control orminor population in studies, which makes these studies harder to identify.

The applications of ASF in rodents varied from wild-type strains (mostly C57BL/6 butalso C3H/HeN and Swiss Webster mice) to models prone to diseases, including irritablebowel disease (IBD) (15–17), type I diabetes (18), or colorectal cancer (19). The ASF lacksProteobacteria, a phylum shared by mice and humans, whereas some researchersintroduced Proteobacteria to ASF mice, such as Oxalobacter formigenes (20) and Esch-erichia coli (21). Other studies included only selected members of the ASF, because notall members were found to successfully colonize the murine cecum (18) or to test thelevels of colonization resistance of different combinations of ASF members (22). Overall,the application of ASF for the study host-microbe interactions has been quite diverse,regarding host strain, gut region of interest, and host parameters studied.

Although the ASF has been used multiple times as a reference microbiota and hasaided in the establishment of other defined microbiota, such as Oligo-MM and theBristol microbiota, its representability of the normal gut microbiota has been criticized(23), as discussed below.

Defined Intestinal Microbial Communities Microbiology and Molecular Biology Reviews



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cadh

erin

pro

tein

exp

ress

ion

and

RegI

II-ga

mm

am

RNA

exp

ress

ion

inco

lon;

surv

ival

,col

itis

dise

ase

seve

rity,

hist

olog

ysc

ore,

and

mye

lop

erox

idas

eac

tivity

afte

rD

SSin

duct

ion;

colo

nic

IL-6

,IL-

10,M

CP-

1,IF

N-c

,TN

F-�

,IL-

12p

70le

vels

17

Mou

seM

ouse

(C57

BL/6

)N

RA

utoc

lave

dfo

odBo

th8–

12w

k(8

–12

wk)

RegI

II-ga

mm

aRN

Aan

dp

rote

inex

pre

ssio

nin

ileum

and

colo

n

176

(Con

tinue

don

next

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e)




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br.asm.org/

Dow

nloaded from


TAB

LE1

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylae

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

df

No.

ofan

imal

s/g

roup

Ch

owSe

xA

ge

(col

lect

ion

tim

e[s]

c )St

udy

outc

ome(

s)d

Refe

ren

ce

Mou

seM

ouse

(C57

BL/6

and

C57

BL/6

TSLP

R�/�

)

3–5

NR

NR

NR

(28

days

)Ex

pre

ssio

nof

thym

icst

rom

ally

mp

hop

oiet

inm

RNA

inin

test

inal

epith

elia

lce

llor

colo

nic

LP(L

P);%

ofC

D4�

Tce

llsse

cret

ing

IL-1

7Aan

dIF

Nga

mm

ain

the

colo

nic

LPan

dM

LN;e

xpan

sion

ofco

loni

cTr

egce

llsin

colo

nic

LPan

dM

LN;e

xpre

ssio

nof

rece

pto

rfo

rTS

LPb

yC

D4�

and

regu

lato

ryT

cells

177

Mou

seM

ouse

(NIH

Swis

s)4

NR

NR

3da

ys(3

days

)St

ruct

ure

ofm

yent

eric

ple

xus,

nerv

ede

nsity

,ave

rage

no.

ofH

uC/D

-pos

itive

mye

nter

icne

uron

sp

erga

nglio

n,ce

llb

ody

size

,and

aver

age

no.

ofnN

OS-

pos

itive

neur

ons

per

mye

nter

icga

nglio

nin

duod

enum

,jej

unum

,and

ileum

;sm

all

inte

stin

alm

otili

ty(f

requ

ency

and

amp

litud

eof

mus

cle

cont

ract

ions

)in

duod

enum

,je

junu

m,a

ndile

umb

efor

ean

daf

ter

gene

ral

neur

alor

spec

ific

nitr

ergi

cb

lock

ade

178

Mou

seM

ouse

(C57

BL/6

)5–

14A

utoc

lave

dm

ouse

bre

eder

’sdi

et(H

arla

n),

unlim

ited

acce

ss

Both

6–12

wk

(3w

k)C

olon

ichi

stol

ogy,

infla

mm

ator

y(M

PO)

activ

ity,

ente

rop

athy

(pre

senc

eof

feca

lal

bum

in),

and

cyto

kine

exp

ress

ion;

feca

lm

icro

bio

tap

rofil

es;c

olon

icge

neex

pre

ssio

n;p

rop

ortio

nof

T-ce

llsu

bty

pes

inco

loni

cLP

and

othe

rm

ucos

alan

dsy

stem

icim

mun

eco

mp

artm

ents

81

ASF

(8sp

ecie

s)(O

ligo-

MM

12

was

also

used

,but

noho

stp

aram

eter

sw

ere

asse

ssed

)

Mou

seM

ouse

(C57

BL/6

)3

(ASF

),5–

23(O

ligo-

MM

)N

RBo

thN

RTh

ickn

esse

sof

tota

lco

lon

and

colo

nin

ner

muc

us(A

SF);

muc

ustu

rnov

ertim

e(A

SF);

alp

hadi

vers

ityin

colo

nan

dce

cum

(Olig

o-M

M)

26

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tinue

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e)




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nloaded from


TAB

LE1

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylae

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

df

No.

ofan

imal

s/g

roup

Ch

owSe

xA

ge

(col

lect

ion

tim

e[s]

c )St

udy

outc

ome(

s)d

Refe

ren

ce

ASF

(8an

d9

spec

ies)

8sp

ecie

s:A

SF9

spec

ies:

ASF

�O

xalo

bact

erfo

rmig

enes

9sp

ecie

s:M

ouse

Mou

se(S

W)

4–7

LM-4

85au

tocl

avab

lero

dent

diet

,fre

eac

cess

M(n

oge

nder

effe

ctob

serv

ed)

3–9

mo

(3–9

mo

�6

wk)

Bact

eria

lle

vels

inst

omac

h,ce

cum

,pro

xim

alco

lon,

and

ceca

lm

ucos

a;b

ody

wt;

diet

ary

oxal

ate

inta

ke;c

ecal

and

feca

lox

alat

ele

vels

;ur

ine

vol;

urin

ary

met

abol

itele

vels

;cec

alw

etw

t;ce

cal

wat

erm

etab

olite

s

20

Part

ial

ASF

(6sp

ecie

s)A

SF35

6,-3

61,-

492,

-502

,-5

19,a

nd-5

00(A

SF36

0an

d-4

57di

dno

tco

loni

ze)

Mou

seM

ouse

(NO

D.M

yD88

KO)

Non

e9–

23N

RBo

thN

R(u

pto

30w

k)In

cide

nce

ofdi

abet

es;

hist

olog

ical

scor

esof

pan

crea

ticis

let

dest

ruct

ion

18

Part

ial

ASF

(4an

d5

spec

ies)

4sp

ecie

s:A

SF36

0,A

SF36

1,A

SF45

7,A

SF51

95

spec

ies:

4sp

ecie

s�

Buty

rivib

riofib

risol

vens

(typ

eI,

ATC

C19

171;

typ

eII,

ATC

C51

255)

4sp

ecie

s:

5sp

ecie

s:

Mou

sean

db

ovin

e

Mou

se(B

ALB

/c)

4–5

Aut

ocla

ved

low

-fib

erdi

et(5

SRZ,

cata

log

no.

1813

680)

,hig

h-fib

erdi

et(5

SVL,

cata

log

no.

1813

901)

,or

trib

utyr

indi

et(5

AVC

,cat

alog

no.1

8149

61)

NR

NR

(2.5

–5m

oaf

ter

colo

rect

alca

ncer

indu

ctio

n)

Col

orec

tal

tum

orm

ultip

licity

,tu

mor

size

,and

tum

orgr

ade;

leve

lsof

LDH

A,

lact

ate,

but

yrat

e,H

3ac,

and

tota

lH

3in

colo

nic

tissu

ean

dtu

mor

s;lu

min

alSC

FAle

vels

;H3a

can

dex

pre

ssio

nle

vels

ofFa

s,p

21,a

ndp

27ge

nes

inco

loni

ctis

sue

and

tum

ors;

apop

tosi

san

dce

llp

rolif

erat

ion

leve

lsin

colo

nic

tissu

ean

dtu

mor

s

19

Part

ial

ASF

(4,5

,7,a

nd7

spec

ies)

4sp

ecie

s:A

SF35

6,A

SF36

0,A

SF36

1,an

dA

SF51

95

spec

ies:

ASF

360,

ASF

361,

ASF

457,

SB2

(ASF

502)

,an

dA

SF51

97

spec

ies:

ASF

356,

ASF

360,

ASF

361,

ASF

457,

ASF

500,

SB2

(ASF

502)

,an

dA

SF51

97

spec

ies:

4sp

ecie

s�

E.co

liM

t1B1

,St

rept

ococ

cus

dani

elia

eER

D01

G,S

taph

yloc

occu

sxy

losu

s33

-ERD

13C

(mor

ew

ithO

ligo-

MM

[see

bel

ow])

4sp

ecie

s:

5sp

ecie

s:

7sp

ecie

s:

7sp

ecie

s:

Mou

seM

ouse

(C57

BL/6

)4–

6N

RBo

th0

or8–

12w

k(8

–12

wk

or40

days

)Fe

cal

bac

teria

lco

nten

t;b

acte

rial

load

ofS.

Typ

him

uriu

min

fece

s,ce

cum

,and

MLN

;rel

ativ

ece

cal

wt;

func

tiona

lge

nom

ican

alys

isof

bac

teria

22

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tinue

don

next

pag

e)




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br.asm.org/

Dow

nloaded from


TAB

LE1

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylae

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

df

No.

ofan

imal

s/g

roup

Ch

owSe

xA

ge

(col

lect

ion

tim

e[s]

c )St

udy

outc

ome(

s)d

Refe

ren

ce

Olig

o-M

M(1

2,15

,and

17sp

ecie

s)12

spec

ies,

Olig

o-M

M:

Acu

talib

acte

rm

uris

KB18

,Fla

voni

frac

tor

plau

tiiYL

31,C

lost

ridiu

mcl

ostr

idio

form

eYL

32,

Blau

tiaco

ccoi

des

YL58

,Cl

ostr

idiu

min

nocu

umI4

6,La

ctob

acill

usre

uter

iI4

9,En

tero

cocc

usfa

ecal

isKB

1,Ba

cter

oide

sca

ecim

uris

I48,

Mur

ibac

ulum

inte

stin

ale

YL27

,Bifi

doba

cter

ium

long

umsu

bsp

.ani

mal

isYL

2,Tu

ricim

onas

mur

isYL

45,A

kker

man

sia

muc

inip

hila

YL44

15sp

ecie

s:12

spec

ies

�3

facu

ltat

ive

anae

rob

es(E

.co

liM

t1B1

,St

rept

ococ

cus

dani

elia

eER

D01

G,S

taph

yloc

occu

sxy

losu

s33

-ERD

13C

)17

spec

ies:

12sp

ecie

s�

5A

SFm

emb

ers

(ASF

360,

ASF

361,

ASF

457,

SB2

[ASF

502]

,ASF

519)

12sp

ecie

s:

15sp

ecie

s:

17sp

ecie

s:

Mou

seM

ouse

(C57

BL/6

)4–

6N

RBo

th0

(8–1

2w

k)Fe

cal

bac

teria

lco

nten

t;b

acte

rial

load

ofS.

Typ

him

uriu

min

fece

s,ce

cum

,and

MLN

;rel

ativ

ece

cal

wt;

func

tiona

lge

nom

ican

alys

isof

bac

teria

22

Olig

o-M

M(1

2an

d13

spec

ies)

12sp

ecie

s:O

ligo-

MM

13sp

ecie

s:12

spec

ies

�Cl

ostr

idiu

msc

inde

nsA

TCC

3570

4

12sp

ecie

s:

13sp

ecie

s:

Mou

seM

ouse

(C57

BL/6

)5–

8N

RN

R0

(6–1

2w

k)Fe

cal

and

ceca

lb

acte

rial

cont

ents

;cec

alle

vels

oflip

ocal

in-2

;cal

pro

tect

inex

pre

ssio

nin

ceca

ltis

sue;

hist

opat

holo

gyof

cecu

m;

ceca

lb

ileac

idm

etab

olom

e

SIH

UM

I(x)

(7an

d8

spec

ies)

:SI

HU

MI:

Ana

eros

tipes

cacc

aeD

SM14

662

orD

SM14

667,

Bact

eroi

des

thet

aiot

aom

icro

nD

SM20

79,B

.lon

gum

NC

C27

05,B

laut

iapr

oduc

taD

SM29

50,C

lost

ridiu

mra

mos

umD

SM14

02,E

.co

liK-

12M

G16

55,

Lact

obac

illus

plan

taru

mD

SM20

174

SIH

UM

I(x)

Clos

trid

ium

buty

ricum

DSM

1070

2

7sp

ecie

s:

8sp

ecie

s:

Hum

anRa

t(S

pra

gue-

Daw

ley)

3–21

Ster

ilize

dst

anda

rdch

ow(2

25g/

kgof

bod

yw

tp

rote

in,5

0g/

kgcr

ude

fat,

65g/

kgas

h,13

5g/

kgm

oist

ure,

480

g/kg

N-f

ree

extr

act)

,fe

rmen

tab

le-

fiber

-fre

edi

et,

inul

indi

et,p

ectin

diet

,and

high

-fat

and

low

-fat

diet

s

Both

0–3

mo

(2–3

8w

k)St

abili

tyof

mic

rob

iota

inof

fsp

ring;

SCFA

conc

nan

dp

Hin

cecu

m,c

olon

,and

fece

s;b

acte

rial

coun

tsin

cecu

m,c

olon

,and

fece

s;M

idtv

edt

crite

ria

27

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tinue

don

next

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e)




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br.asm.org/

Dow

nloaded from


TAB

LE1

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylae

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

df

No.

ofan

imal

s/g

roup

Ch

owSe

xA

ge

(col

lect

ion

tim

e[s]

c )St

udy

outc

ome(

s)d

Refe

ren

ce

SIH

UM

I(x)

(8an

d9

spec

ies)

8sp

ecie

s:SI

HU

MI(x

)9

spec

ies:

8sp

ecie

s�

A.

muc

inip

hila

ATC

CBA

A-8

35

9sp

ecie

s:H

uman

Mou

se(C

3H)

5–10

NR

NR

12w

k(5

–15

days

)Ba

cter

ial

cell

no.a

ndp

rop

ortio

nsin

cecu

man

dco

lon;

ceca

lan

dco

loni

chi

stop

atho

logy

scor

es;

exp

ress

ion

ofp

roin

flam

mat

ory

cyto

kine

sin

ceca

lan

dco

loni

cm

ucos

a;se

rum

pro

tein

leve

lsof

pro

infla

mm

ator

ycy

toki

nes;

no.o

fS.

Typ

him

uriu

mce

llsin

MLN

and

sple

en;s

ize;

mac

rop

hage

infil

trat

ion

ince

cal

tissu

e;lo

caliz

atio

nof

A.m

ucin

iphi

laan

dS.

Typ

him

uriu

m;m

ucin

form

atio

n,m

ucus

thic

knes

s,m

ucus

com

pos

ition

,and

no.

ofm

ucin

-fille

dce

lls

28

SIH

UM

I(x)

(8an

d9

spec

ies)

8sp

ecie

s:SI

HU

MI(x

)9

spec

ies:

8sp

ecie

s�

Fuso

bact

eriu

mva

rium

ATC

C85

01

9sp

ecie

s:H

uman

Mou

se(C

3H/H

eOuJ

)12

Irra

diat

edst

anda

rdch

owR0

3-40

F0

(8w

k)Bo

dyw

t;dr

ym

ass

ofce

cum

and

colo

n;b

acte

rial

cont

ent

ince

cum

and

colo

n;p

olya

min

eco

ncn

ince

cum

and

colo

n;SC

FAco

ncn

ince

cum

and

colo

n;hi

stol

ogy

ofce

cum

and

dist

alco

lon

(thi

ckne

sses

ofcr

ypt,

epith

elia

lla

yer,

muc

osa,

sub

muc

osa,

mus

cula

risex

tern

a);m

itosi

san

dap

opto

sis

ofce

cal

and

dist

alco

loni

ctis

sue

30

Hum

anM

ouse

(Prm

/Alf,

C3H

/He)

12–1

3St

erili

zed

pel

lete

dst

anda

rdch

owR0

3-40

F0

(56

�1

days

)Le

ngth

sof

smal

l,la

rge,

and

who

lein

test

ines

;th

ickn

esse

sof

mus

cle,

cryp

t,an

dvi

lliin

pro

xim

alan

dsm

all

inte

stin

ean

dco

lon;

feca

lan

dce

cal

mic

rob

ial

cont

ents

;cec

alco

ncn

ofSC

FAs

and

pol

yam

ines

31

(Con

tinue

don

next

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e)




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br.asm.org/

Dow

nloaded from


TAB

LE1

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylae

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

df

No.

ofan

imal

s/g

roup

Ch

owSe

xA

ge

(col

lect

ion

tim

e[s]

c )St

udy

outc

ome(

s)d

Refe

ren

ce

SIH

UM

I(x)

(7an

d8

spec

ies)

7sp

ecie

s:SI

HU

MI(x

)w

ithou

tC.

ram

osum

8sp

ecie

s:SI

HU

MI(x

)

7sp

ecie

s:

8sp

ecie

s:

Hum

anM

ouse

(C3H

/HeO

uJ)

3–9

Irra

diat

edlo

w-f

ator

high

-fat

diet

adlib

itum

M0

(16

wk)

Body

wt;

%bo

dyfa

t;ad

ipos

etis

sue

wt

(epi

didy

mal

,m

esen

teric

,and

subc

utan

eous

);en

ergy

inta

ke;

food

effic

ienc

y;di

gest

ibili

tyof

high

-fat

diet

;dig

estib

leen

ergy

;ce

cala

ndco

loni

cba

cter

ial

cont

ents

per

spec

ies;

bloo

dgl

ucos

e;le

ptin

gene

expr

essio

nin

epid

idym

altis

sue;

liver

wt;

liver

trig

lyce

ride

leve

ls;liv

ergl

ycog

enco

nten

ts;

expr

essio

nof

gene

sin

volv

edin

lipid

tran

spor

t,lip

idsy

nthe

sis,c

hole

ster

olsy

nthe

sis,

and

lipid

cata

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m;g

ene

expr

essio

nof

prot

eins

invo

lved

insm

alli

ntes

tinal

gluc

ose

upta

ke;S

CFA

form

atio

nin

cecu

m,c

olon

,and

port

alve

inpl

asm

a;ge

neex

pres

sion

ofSC

FA-re

late

dpr

otei

nsin

colo

nic

muc

osa;

gene

expr

essio

nof

lipid

tran

spor

tan

dst

orag

epr

otei

nsin

ileum

;pa

ram

eter

sof

inte

stin

alpe

rmea

bilit

yan

dlo

w-g

rade

infla

mm

atio

n

32

SIH

UM

I(x)

(8an

d9

spec

ies)

8sp

ecie

s:SI

HU

MI(x

)9

spec

ies:

8sp

ecie

s�

A.

muc

inip

hila

ATC

CBA

A-8

35

9sp

ecie

s:H

uman

Mou

se(C

57BL

/6.

129P

2-Il1

0tm

1Cgn

)

5–6

Irra

diat

edst

anda

rdch

ow(f

ortifi

edty

pe

1310

;A

ltro

min

,Lag

e,G

erm

any)

adlib

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M0

or8

wk

(3w

k)Bo

dyw

t;hi

stop

atho

logy

scor

esin

subm

ucos

a,LP

,sur

face

epith

eliu

m,a

ndlu

men

;col

onle

ngth

;rel

ativ

em

RNA

leve

lsof

Tnfa

,Ifn

g,an

dRe

g3g;

feca

llip

ocal

in-2

conc

n;fe

cala

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calb

acte

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s;ce

cal

hist

olog

y;no

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tce

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r10

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ince

cum

and

colo

n;m

ucus

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ess

inco

lon;

rela

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Muc

2m

RNA

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dist

alsm

alli

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cecu

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lon

29

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bb

revi

atio

ns:M

,mal

e;F,

fem

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SW,S

wis

sW

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P,la

min

ap

rop

ria;M

LN,m

esen

teric

lym

ph

node

s;M

PO,m

yelo

per

oxid

ase;

NR,

not

rep

orte

d;SC

FA,s

hort

-cha

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tty

acid

;Tre

gce

ll,re

gula

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Tce

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days

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F-�

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pan

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the

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ctin

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;,V

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,oth

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from

left

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htin

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illus

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,duo

denu

m;

,jej

unum

;,i

leum

;,c

ecum

;,c

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ectu

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,fec

es.




http://mm

br.asm.org/

Dow

nloaded from


TAB

LE2

Stud

ies

usin

gno

n-sp

ecifi

cally

-nam

edde

fined

com

mun

ities

inro

dent

sto

stud

yho

st-m

icro

be

inte

ract

ions

invi

vo(n

�16

)a

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

,F-s

trai

ns,a

ndN

-str

ains

(2,9

,11,

41,a

nd13

0sp

ecie

s)2

spec

ies:

E.co

liC

25�

Lact

obac

illus

9sp

ecie

s:2

spec

ies

�En

tero

cocc

us�

Lact

obac

illus

�Ca

ndid

a�

4m

orp

holo

gica

llydi

ffer

ent

stra

ins

ofG

ram

-neg

ativ

ean

aero

bes

11sp

ecie

s:9

spec

ies

�2

stra

ins

ofG

ram

-ne

gativ

ean

aero

bes

with

fusi

form

mor

pho

logy

41sp

ecie

s:11

spec

ies

�30

addi

tiona

lst

rain

sof

Gra

m-n

egat

ive

anae

rob

es13

0sp

ecie

s:50

stra

ins

ofG

ram

-neg

ativ

est

rict

anae

rob

es(N

)�

80fa

cult

ativ

ean

aero

bes

(F)

2sp

ecie

s:

Oth

ers

not

spec

ified

Mou

seM

ouse

(CD

-1)

4–57

Aut

ocla

ved

Lob

und

diet

L-35

6or

pel

lete

dst

erile

diet

from

Cha

rles

Rive

rM

ouse

Farm

s

NR

NR

(1–6

0da

ys)

Cec

alnu

mb

erof

E.co

liC

25b

acte

ria;c

ecal

size

;hi

stop

atho

logy

ofst

omac

h,sm

all

inte

stin

e,ce

cum

,and

colo

n

33

N-

and

F-st

rain

s(6

0,96

,and

97sp

ecie

s)60

spec

ies:

N-s

trai

ns�

14fa

cult

ativ

ean

aero

bes

�E.

coli

C25

96st

rain

s:F-

stra

ins

�E.

coli

C25

,E.c

oli

40T,

orSh

igel

la97

stra

ins:

F-st

rain

s�

E.co

liC

25�

Shig

ella

orE.

coli

40T

Not

spec

ified

Mou

seM

ouse

(CD

-1)

5–75

Ster

ilize

dLo

bun

ddi

etL-

356,

Cha

rles

Rive

rfo

rmul

a7R

F,Lo

bun

ddi

etL-

485,

orPu

rina

bre

eder

chow

NR

NR

(4w

k)C

ecal

size

;cec

alle

vels

offa

tty

acid

s;ce

cal

leve

lsof

E.co

li;p

Hof

ceca

lco

nten

ts

34

NA

(4sp

ecie

s)La

ctob

acill

ussp

ecie

s1

and

2,Ba

cter

oide

ssp

.,St

rept

ococ

cus

grou

pN

Rat?

Rat

(Sp

ragu

e-D

awle

y)N

one

2A

utoc

lave

dst

anda

rddi

ete

sup

ple

men

ted

with

caff

eic

acid

NR

NR

Urin

ary

met

abol

ites

ofca

ffei

cac

ids

179

(Con

tinue

don

next

pag

e)




http://mm

br.asm.org/

Dow

nloaded from


TAB

LE2

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

(2,2

,2,2

,3,3

,4,5

,6,6

,6,

8,8,

9,13

,15,

and

17sp

ecie

s)2

spec

ies:

Act

inob

acill

uss3

�St

rept

ococ

cus

s12

spec

ies:

Bact

eroi

des

s8�

Act

inob

acill

uss3

2sp

ecie

s:Eu

bact

eriu

ms1

0�

Mic

roco

ccus

s62

spec

ies:

Clos

trid

ium

C1

�C

23

spec

ies:

Bact

eroi

des

s8�

Act

inob

acill

uss3

�E.

coli

s73

spec

ies:

Shig

ella

flexn

eri

�C

5�

C6

4sp

ecie

s:C

1–C

44

spec

ies:

S.fle

xner

i�

C3–

C5

6sp

ecie

s:C

1–C

66

spec

ies:

Act

inob

acill

uss3

�St

rept

ococ

cus

s1�

Lact

obac

illus

s4�

Cory

neba

cter

ium

s5�

Mic

roco

ccus

s6�

Stre

ptoc

occu

ss2

6sp

ecie

s:S.

flexn

eri

�C

5–C

98

spec

ies:

6sp

ecie

s(A

ctin

obac

illus

,etc

.)�

Bact

eroi

des

s8�

E.co

lis7

8sp

ecie

s:S.

flexn

eri

�C

3–C

99

spec

ies:

C1–

C9

13sp

ecie

s:C

1–C

1315

spec

ies:

C1–

1517

spec

ies:

8sp

ecie

s(A

ctin

obac

illus

,etc

.)�

C1–

C9

2sp

ecie

s(2

�):

2sp

ecie

s:

3sp

ecie

s:

6sp

ecie

s:

8sp

ecie

s:

4,9,

13,a

nd15

spec

ies:

17sp

ecie

s:

Hum

anan

dm

ouse

Mou

se(C

D-1

)�

2St

erili

zed

com

mer

cial

diet

(Usi

ned’

Alim

enta

tion

Ratio

nnel

le)

adlib

itum

Both

2–5

mo

(4w

kaf

ter

last

inoc

ulat

ion)

No.

ofIg

Ap

lasm

ocyt

esin

duod

enum

38

(Con

tinue

don

next

pag

e)




http://mm

br.asm.org/

Dow

nloaded from


TAB

LE2

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

(2,2

,2,2

,2,2

,2,2

,and

3sp

ecie

s)2

and

2sp

ecie

s:Cl

ostr

idiu

mE

orP

with

E.co

liK-

122

spec

ies

(�6)

:Clo

strid

ium

E�

E.co

liS,

Prot

eus

mira

bilis

,Kle

bsie

llapn

eum

onia

e,Ba

cter

oide

s(A

listip

es)

putr

edin

is,

Veill

onel

laal

cale

scen

s,or

Clos

trid

ium

perf

ringe

ns3

spec

ies:

Clos

trid

ium

Ean

dP

�E.

coli

K-12

2sp

ecie

s(5

�):

2sp

ecie

s:

2sp

ecie

s(2

�):

3sp

ecie

s:

Mou

se,

rat,

hum

an

Mou

se(C

3H)

2–6

Aut

ocla

ved

com

mer

cial

diet

NR

Adu

lt(u

pto

51da

ys)

Feca

lb

acte

rial

coun

ts;

(muc

osal

)hi

stol

ogy

ofst

omac

h,je

junu

m,i

leum

,ce

cum

,and

colo

n

180

UW

-GL

(9sp

ecie

s)G

ener

aLa

ctob

acill

us,

Baci

llus,

Clos

trid

ium

and

Cory

neba

cter

ium

Spec

ies

not

defin

ed?

�p

hyla

know

n,b

utex

act

com

pos

ition

not

defin

ed

NR

Mou

se(B

ALB

/c)

Tota

lof

3St

erili

zed

Rals

ton

Purin

adi

et50

10C

Both

0(6

0–90

days

)C

ecal

leve

lsof

bac

teria

and

Cand

ida

albi

cans

;hi

stol

ogy

ofto

ngue

and

stom

ach

37

NA

(6sp

ecie

s)St

rept

ococ

cus

(Ent

eroc

occu

s)fa

ecal

is,

Lact

obac

illus

brev

is,

Aer

obac

ter

aero

gene

s,St

aphy

loco

ccus

epid

erm

idis

,Bac

tero

ides

spur

ius

(?),

aye

ast

fung

us

?�

phy

lum

coul

dno

tb

ere

trie

ved

NR

Mou

se(B

ALB

/c/A

BOM

f)N

one

3–6

Ster

ilize

dfo

od(2

diff

eren

tp

roce

dure

s)N

R0

(14

wk)

Seru

mle

vels

ofIg

G1,

IgG

2,Ig

M,a

ndIg

A10

8

Part

ial

orco

mp

lete

UW

-GL

(2,3

,and

9sp

ecie

s)2

spec

ies:

Lact

obac

illus

�Cl

ostr

idiu

m3

spec

ies:

2sp

ecie

s�

Baci

llus

9sp

ecie

s:U

W-G

L

2,3

spec

ies:

NR

and

mou

seM

ouse

(HA

/IC

R)10

–48

NR

Both

Adu

lt(1

4–56

days

)

Dea

thaf

ter

C.bo

tulin

umin

fect

ion;

feca

lC.

botu

linum

toxi

nex

cret

ion;

colo

niza

tion

pat

tern

ofC.

botu

linum

36

(Con

tinue

don

next

pag

e)




http://mm

br.asm.org/

Dow

nloaded from


TAB

LE2

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

(2sp

ecie

s)B.

thet

aiot

aom

icro

nVP

I-54

82�

Des

ulfo

vibr

iopi

ger

ATC

C29

098

Hum

anM

ouse

(NM

RI/K

I)4–

5A

utoc

lave

dp

olys

acch

arid

e-ric

hdi

et(B

&K)

adlib

itum

M(s

ubse

t)A

dult

or12

wk

(14–

28da

ys)

Bact

eria

lco

nten

tsin

cecu

man

ddi

stal

colo

n;b

acte

rial

gene

exp

ress

ion;

glyc

anle

vels

ince

cum

;SC

FAp

rodu

ctio

nin

cecu

m;

seru

mac

etat

e;liv

ertr

igly

cerid

es;e

pid

idym

alfa

tp

ad

109

NA

(2,6

,and

10sp

ecie

s)2

spec

ies:

Stap

hylo

cocc

usep

ider

mid

is�

Veill

onel

lapa

rvul

a6

and

10sp

ecie

s:an

aero

bic

stra

ins

isol

ated

from

aco

nven

tiona

lm

ale

mou

se(n

otsp

ecifi

ed)

2sp

ecie

s:M

ouse

Mou

se(B

10.B

R)45

–73

Ster

ilize

dST

1(In

stitu

teof

Phys

iolo

gyA

SC

R)M

21da

ys(1

2m

o)O

ccur

renc

eof

anky

losi

ngen

thes

opat

hyof

the

ankl

e;co

lon

hist

olog

y;b

acte

rial

cont

ents

inile

uman

dco

lon

181

NA

(2sp

ecie

s)B.

thet

aiot

aom

icro

n�

Euba

cter

ium

rect

ale

Hum

anM

ouse

(NM

RI/K

I)4–

5Ir

radi

ated

stan

dard

low

-fa

t,p

lant

pol

ysac

char

ide-

rich

diet

(die

t20

18fr

omH

arla

ndTe

klad

);hi

gh-f

at,“

high

-sug

ar”

Wes

tern

-typ

edi

et(c

atal

ogno

.961

32;

Har

lan

Tekl

ad);

orlo

w-f

at,h

igh-

suga

rdi

et(c

atal

ogno

.03

317;

Har

lan

Tekl

ad)

M11

wk

(14

days

)Ba

cter

ial

gene

exp

ress

ion;

ceca

lco

loni

zatio

nle

vels

;fe

rmen

tatio

nef

ficie

ncy

ince

cum

;col

onic

gene

exp

ress

ion;

pro

tein

exp

ress

ion

ince

cum

85

NA

(3,8

,9,a

nd10

spec

ies)

3sp

ecie

s:E.

coli

HS,

Bact

eroi

des

vulg

atus

DSM

1447

,B.

thet

aiot

aom

icro

nD

SM20

798

spec

ies:

3sp

ecie

s�

B.lo

ngum

NC

C27

05,

Blau

tiaha

nsen

iiD

SM20

583,

C.sc

inde

nsD

SM56

76,E

ubac

teriu

mve

ntrio

sum

DSM

3988

,La

ctob

acill

usrh

amno

sus

NC

C40

079

spec

ies:

8sp

ecie

s�

Colli

nsel

laae

rofa

cien

sD

SM39

79(c

olon

ized

mos

tm

ice)

10sp

ecie

s:9

spec

ies

�Fa

ecal

ibac

teriu

mpr

ausn

itzii

DSM

1767

7(d

idno

tco

loni

zem

ice)

3sp

ecie

s:

8sp

ecie

s:

9sp

ecie

s:

10sp

ecie

s:

Hum

anM

ouse

(C3H

/HeN

)15

in tota

lSt

erile

stan

dard

chow

diet

orsw

itch

tohi

gh-f

atdi

etad

libitu

m

Both

7w

k(7

0da

ysaf

ter

1st

inoc

ulat

ion)

Feca

lan

dce

cal

bac

teria

lce

llco

unts

;bod

yw

t;m

etab

olite

sin

urin

ean

dp

lasm

a

39

(Con

tinue

don

next

pag

e)




http://mm

br.asm.org/

Dow

nloaded from


TAB

LE2

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

(15

and

19sp

ecie

s)15

spec

ies:

Bact

eroi

des

cacc

ae,B

acte

roid

esov

atus

,B.

thet

aiot

aom

icro

n,Ba

cter

oide

sun

iform

is,B

.vu

lgat

us,B

acte

roid

esst

rain

WH

2,C.

scin

dens

,Cl

ostr

idiu

msp

irofo

rme,

C.ae

rofa

cien

s,D

orea

long

icat

ena,

E.re

ctal

e,F.

prau

snitz

ii,Pa

raba

cter

oide

sdi

stas

onis

,Rum

inoc

occu

sob

eum

,Rum

inoc

occu

sto

rque

s(s

trai

nin

form

atio

nno

tac

cess

ible

)19

spec

ies:

15sp

ecie

s�

Bifid

obac

teriu

man

imal

issu

bsp

.lac

tisC

NC

MI-2

494,

Lact

obac

illus

delb

ruec

kii

sub

sp.b

ulga

ricus

CN

CM

I-163

2�

CN

CM

I-151

9,La

ctoc

occu

sla

ctis

sub

sp.

crem

oris

CN

CM

I-163

1,an

dSt

rept

ococ

cus

ther

mop

hilu

sC

NC

MI-1

630

15sp

ecie

s:

19sp

ecie

s:

Hum

anM

ouse

(C57

BL/6

J)5

Aut

ocla

ved

low

-fat

,p

lant

pol

ysac

char

ide-

rich

diet

(B&

Kra

tan

dm

ouse

auto

clav

able

chow

,cat

alog

no.

7378

000)

M6–

8 wk

(42

days

)

Feca

lan

dce

cal

bac

teria

lco

nten

t;b

acte

rial

gene

exp

ress

ion;

urin

ary

met

abol

ites

40

NA

(2sp

ecie

s)B.

thet

aiot

aom

icro

nVP

I-54

82(A

TCC

2914

8)�

F.pr

ausn

itzii

A2-

165

(DSM

1767

7)

Hum

anRa

t(F

344)

6–16

Irra

diat

edp

olys

acch

arid

e-ric

hdi

et(R

03,S

AFE

)

M�

3m

o(3

0da

ysaf

ter

inoc

ulat

ion

ofF.

prau

snitz

ii)

Hos

tge

neex

pre

ssio

nin

colo

nic

epith

eliu

m;c

ecal

SCFA

conc

n;ox

idor

educ

tion

pot

entia

lin

ceca

lco

nten

ts;

colo

nic

cryp

tde

pth

;to

tal

cells

/cry

pt

inco

lon;

exp

ress

ion

ofdi

ffer

entia

tion

pro

tein

sof

secr

etor

ylin

eage

(KLF

-4,C

hgA

);M

uc2

pro

duct

ion

inco

loni

cep

ithel

ium

;col

onic

muc

ingl

ycos

ylat

ion

182

(Con

tinue

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next

pag

e)




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br.asm.org/

Dow

nloaded from


TAB

LE2

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

(2sp

ecie

s)B.

thet

aiot

aom

icro

nVP

I-54

82�

B.lo

ngum

NC

C27

05

Hum

anM

ouse

(SW

)3

Stan

dard

diet

(Pur

ina

Lab

Die

t5K

67)

NR

NR

(10

days

)Fe

cal

bac

teria

lco

nten

t;m

etab

olite

sin

fece

san

dur

ine

86

NA

(2,8

,and

9sp

ecie

s)2

spec

ies:

B.th

etai

otao

mic

ron

�D

.pi

ger

8sp

ecie

s:B.

thet

aiot

aom

icro

n,B.

cacc

ae,B

.ova

tus,

E.re

ctal

e,M

arvi

nbry

antia

form

atex

igen

s,C.

aero

faci

ens,

E.co

li,Cl

ostr

idiu

msy

mbi

osum

9sp

ecie

s:8

spec

ies

�D

.pi

ger

2sp

ecie

s:

8sp

ecie

s:

9sp

ecie

s:

Hum

anM

ouse

(NM

RI)

4–20

Irra

diat

edlo

w-f

at/h

igh-

pla

nt-p

olys

acch

arid

eor

high

-fat

/hig

h-si

mp

le-s

ugar

diet

adlib

itum

,HF/

HS

diet

with

mod

ified

sulfa

teco

ncn

(600

-fol

dra

nge)

,or

HF/

HS

diet

sup

ple

men

ted

with

chon

droi

tinsu

lfate

M7–

8w

k(2

wk)

Feca

lb

acte

rial

rela

tive

abun

danc

e;fe

cal

met

atra

nscr

ipto

me;

gene

exp

ress

ion

ofD

.pig

er;

gene

exp

ress

ion

ofm

ouse

pro

xim

alco

lon;

ceca

lm

etab

olite

s

42

NA

(14

spec

ies)

�vi

rusl

ike

par

ticle

sC.

aero

faci

ens

ATC

C25

986,

B.ca

ccae

ATC

C43

185,

B.ov

atus

ATC

C84

83,B

.th

etai

otao

mic

ron

VPI-

5482

�73

30,

Bact

eroi

des

unifo

rmis

ATC

C84

92,B

acte

roid

esvu

lgat

usA

TCC

8482

,Ba

cter

oide

sce

llulo

sily

ticus

WH

2,Pa

raba

cter

oide

sdi

stas

onis

ATC

C85

03,C

.sc

inde

nsA

TCC

3570

4,C.

sym

bios

umA

TCC

1494

0,C.

spiro

form

eD

SM15

52,

D.l

ongi

cate

naD

SM13

814,

E.re

ctal

eA

TCC

3365

6,R.

obeu

mA

TCC

2917

4

Hum

anM

ouse

(C57

BL/6

J)5

Aut

ocla

ved

low

-fat

/hi

gh-p

lant

-p

olys

acch

arid

edi

et(B

&K)

adlib

itum

NR

8w

k(4

6da

ys)

Gut

bar

rier

and

imm

une

func

tion;

over

all

heal

thst

atus

;bod

yw

tan

dad

ipos

ity;n

o.of

CD

4�

and

CD

8�T

cells

insp

leen

san

dM

LN;f

ecal

bac

teria

lco

nten

tan

dvi

ral

abun

danc

e;ge

netic

chan

ges

upon

vira

lat

tack

(pha

gere

sist

ance

);b

acte

rial

cont

ents

ofp

roxi

mal

and

dist

alsm

all

inte

stin

es,c

ecum

,and

colo

n;p

rop

hage

activ

atio

n

45

(Con

tinue

don

next

pag

e)




http://mm

br.asm.org/

Dow

nloaded from

http://www.rcsb.org/pdb/explore/explore.do?structureId=5K67https://mmbr.asm.orghttp://mmbr.asm.org/

TAB

LE2

(Con

tinue

d)

Con

sort

ium

(no.

ofsp

ecie

sb)

Div

isio

nof

ph

ylaf

Stra

inso

urce

(s)

Hos

tsp

ecie

s(s

trai

n)

Part

ofth

eg

utst

udie

dg

No.

ofan

imal

s/g

roup

Ch

owSe

x

Ag

e(c

olle

ctio

nti

me[

s]c )

Stud

you

tcom

e(s)

dRe

fere

nce

NA

(14

spec

ies)

B.ov

atus

DSM

1896

,Ba

cter

oide

sun

iform

isD

SM84

92,B

.th

etai

otao

mic

ron

DSM

2079

,B.c

acca

eD

SM19

024,

Barn

esie

llain

test

inih

omin

isYI

T118

60,R

oseb

uria

inte

stin

alis

1461

0(L

1-82

),E.

rect

ale

DSM

1762

9(A

1-86

),F.

prau

snitz

iiD

SM17

677

(A2-

165)

,Mar

vinb

ryan

tiafo

rmat

exig

ens

DSM

1446

9(I-

52),

C.sy

mbi

osum

DSM

934,

C.ae

rofa

cien

sD

SM39

79,

E.co

liH

S,A

.muc

inip

hila

DSM

2295

9M

uc,D

.pi

ger

ATC

C29

098

Hum

anM

ouse

(SW

)To

tal

of51

Aut

ocla

ved

stan

dard

fiber

-ric

h(1

5%di

etar

yfib

er),

fiber

-fr

ee,o

rp

reb

iotic

(add

ition

ofp

urifi

edso

lub

legl

ycan

s)di

etad

libitu

m

Both

8–9

wk

(54

days

)

Mic

rob

ial

com

pos

ition

infe

ces,

cecu

m,c

olon

iclu

men

,and

muc

usla

yer;

bac

teria

lC

AZy

me

exp

ress

ion

ince

cum

;m

ucin

-sp

ecifi

ctr

ansc

ripts

inB.

cacc

ae,A

.m

ucin

iphi

la,a

ndB.

thet

aiot

aom

icro

n;ce

cal

mic

rob

ial

enzy

me

activ

ities

;lev

els

ofSC

FAs

and

orga

nic

acid

s;co

loni

cm

ucus

laye

rth

ickn

ess;

colo

nic

exp

ress

ion

ofm

ucus

-p

rodu

ctio

n-re

late

dge

nes;

no.o

fgo

ble

tce

llsin

colo

n;hi

stop

atho

logy

;b

ody

wt;

feca

llip

ocal

in;

colo

nle

ngth

;cec

altr

ansc

ripto

me;

afte

rin

fect

ion

with

C.ro

dent

ium

,his

tolo

gica

lsc

ores

ofce

cum

and

colo

n,ar

eaof

infla

med

tissu

ein

cecu

m,s

urvi

val,

asce

ndin

gan

dde

scen

ding

colo

nan

dre

ctum

,adh

eren

tC.

rode

ntiu

mb

acte

riain

colo

n

43

aA

bb

revi

atio

ns:N

A,c

onso

rtiu

mna

me

not

avai

lab

le/a

pp

licab

le;A

SC

R,A

cade

my

ofSc

ienc

esof

the

Cze

chRe

pub

lic;C

hgA

,chr

omog

rani

nA

;KLF

the use of deﬁned microbial communities to model host … · microbial communities are outlined,...

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