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Abstract

Objective A low FODMAP (Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols) diet reduces symptoms of IBS, but reduction of potential prebiotic and fermentative effects might adversely affect the colonic microenvironment. The effects of a low FODMAP diet with a typical Australian diet on biomarkers of colonic health were compared in a single-blinded, randomised, cross-over trial. Design Twenty-seven IBS and six healthy subjects were randomly allocated one of two 21-day provided diets, differing only in FODMAP content (mean (95% CI) low 3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6) g/day), and then crossed over to the other diet with ≥21-day washout period. Faeces passed over a 5-day run-in on their habitual diet and from day 17 to day 21 of the interventional diets were pooled, and pH, short-chain fatty acid concentrations and bacterial abundance and diversity were assessed. Results Faecal indices were similar in IBS and healthy subjects during habitual diets. The low FODMAP diet was associated with higher faecal pH (7.37 (7.23 to 7.51) vs 7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty acid concentrations, greater microbial diversity and reduced total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83 (9.72 to 9.93) log10 copies/g; p<0.001) compared with the Australian diet. To indicate direction of change, in comparison with the habitual diet the low FODMAP diet reduced total bacterial abundance and the typical Australian diet increased relative abundance for butyrate-producing Clostridium cluster XIVa (median ratio 6.62; p<0.001) and mucus-associated Akkermansia muciniphila (19.3; p<0.001), and reduced Ruminococcus torques. Conclusions Diets differing in FODMAP content have marked effects on gut microbiota composition. The implications of long-term reduction of intake of FODMAPs require elucidation. Trial registration number ACTRN12612001185853.
ORIGINAL ARTICLE
Diets that differ in their FODMAP content alter the
colonic luminal microenvironment
Emma P Halmos,
1,2
Claus T Christophersen,
3
Anthony R Bird,
3
Susan J Shepherd,
1
Peter R Gibson,
1,2
Jane G Muir
1,2
Additional material is
published online only. To view
please visit the journal online
(http://dx.doi.org/10.1136/
gutjnl-2014-307264).
1
Department of Gastr oenterology ,
Eastern Health Clinical School,
Monash University , Box Hill,
Victoria, Austr alia
2
Department of
Gastroenterology, Central
Clinical School, Monash
University, Melbourne, Victoria,
Australia
3
Food Futures National
Research Flagship,
Commonwealth Scientic and
Industrial Research
Organisation, Food, Animal
and Health Sciences, Adelaide,
South Australia, Australia
Correspondence to
Dr Emma P Halmos,
Department of
Gastroenterology, Central
Clinical School, Monash
University, Level 6 The Alfred
Centre, 99 Commercial Road,
Melbourne, VIC 3004,
Australia; Emma.Halmos@
monash.edu
Received 18 March 2014
Revised 9 June 2014
Accepted 24 June 2014
Published Online First
12 July 2014
To cite: Halmos EP,
Christophersen CT, Bird AR,
et al. Gut 2015;64:93100.
ABSTRACT
Objective A low FODMAP (Fermentable
Oligosaccharides, Disaccharides, Monosaccharides And
Polyols) diet reduces symptoms of IBS, but reduction of
potential prebiotic and fermentative effects might adversely
affect the colonic microenvironment. The effects of a low
FODMAP diet with a typical Australian diet on biomarkers
of colonic health were compared in a single-blinded,
randomised, cross-over trial.
Design Twenty-seven IBS and six healthy subjects were
randomly allocated one of two 21-day provided diets,
differing only in FODMAP content (mean (95% CI) low
3.05 (1.86 to 4.25) g/day vs Australian 23.7 (16.9 to 30.6)
g/day), and then crossed over to the other diet with 21-
day washout period. Faeces passed over a 5-day run-in on
their habitual diet and from day 17 to day 21 of the
interventional diets were pooled, and pH, short-chain fatty
acid concentrations and bacterial abundance and diversity
were assessed.
Results Faecal indices were similar in IBS and healthy
subjects during habitual diets. The low FODMAP diet was
associated with higher faecal pH (7.37 (7.23 to 7.51) vs
7.16 (7.02 to 7.30); p=0.001), similar short-chain fatty
acid concentrations, greater microbial diversity and reduced
total bacterial abundance (9.63 (9.53 to 9.73) vs 9.83
(9.72 to 9.93) log
10
copies/g; p<0.001) compared with
the Australian diet. To indicate direction of change, in
comparison with the habitual diet the low FODMAP diet
reduced total bacterial abundance and the typical
Australian diet increased relative abundance for butyrate-
producing Clostridium cluster XIVa (median ratio 6.62;
p<0.001) and mucus-associated Akkermansia muciniphila
(19.3; p<0.001), and reduced Ruminococcus torques.
Conclusions Diets differing in FODMAP content have
marked effects on gut microbiota composition.
The implications of long-term reduction of intake of
FODMAPs require elucidation.
Trial registration numb er ACTRN12612001185853.
INTRODUCTION
IBS often requires multimodal management
approaches that include psychological, dietary and
pharmacological domains. Dietary therapies are
gaining popularity as evidence of efcacy for
specic diets have emerged. One strategy is to restrict
intake of poorly absorbed short-chain carbohydrates,
termed FODMAPs (F ermentable Oligosaccharides,
Disaccharides, Monosaccharides And Polyols). The
evidence-base for efcacy of the low FODMAP diet
is building
15
with a recent blinded placebo-
controlled cross-over study conrming pr evious
studies that about 75% of patients gain clinically sig-
nicant benet.
6
The low FODMAP diet is increas-
ingly being applied by health professionals in patients
with IBS as rst-line therapy.
56
Given the high preva-
lence and chronic nature of IBS, it is possible that
many people will restrict intake of FODMAPs over
months to years.
2
Signicance of this study
What is already known on this subject?
A diet low in Fermentable Oligosaccharides,
Disaccharides, Monosaccharides And Polyols
(FODMAPs) reduces GI symptoms in
approximately 75% of patients with IBS.
FODMAPs are fermentable substrates and some
have prebiotic effects with putative benets on
colonic health.
A randomised parallel group study showed a
reduction of the proportion and concentration of
faecal Bidobacteria spp on a dietitian-taught
low FODMAP diet compared with a habitual diet.
What are the new ndings?
Diets that differ in their FODMAP content are
associated with considerable changes to the
structure of the faecal microbiota.
A provided low FODMAP diet reduces total
bacterial abundance but has no effect on
relative abundance of bacteria putatively
associated with colonic health.
The higher FODMAP intake of the provided
typical Australian diet compared with that of the
low FODMAP or habitual diets was associated
with specic stimulation of the growth of
bacterial groups with putative health benets.
No alterations in faecal short-chain fatty acid
concentrations were associated with differences
in FODMAP ingestion.
How might it impact on clinical practice in
the foreseeable future?
A low FODMAP diet should not be
recommended for asymptomatic populations.
Caution should be taken when recommending
the low FODMAP diet long-term.
Liberalising FODMAP restriction to the level of
adequate symptom control should be exercised
to use the potential health benets of higher
FODMAP intake on the gut microbiota.
Gut microbiota
Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264 93
FODMAPs are being increasingly used in food industry as
prebiotics, either formulated into various types of products or
manufactured as supplements, to promote colonic health.
Evidence is strong for the prebiotic actions of oligosacchar-
ides.
79
Reduced FODMAP delivery to colonic microbiota
might, therefore, have deleterious effects on the growth of bac-
teria with potentially favourable health effects. Indeed, a rando-
mised parallel group study where the effects on faecal
microbiota of a dietitian-taught low FODMAP diet compared
with those of a habitual diet indicated a reduction of the pro-
portion and concentration of Bidobacteria spp,
4
providing the
rst evidence for potentially unfavourable effects of the diet.
FODMAPs are also substrates for fermentation by bacteria
not considered to be prebiotic.
10
Bacterial fermentation of car-
bohydrates yields short-chain fatty acids (SCFAs), including
butyrate, the major energy substrate for the colonic epithe-
lium.
11 12
Butyrate is also a key regulator of colonocyte prolifer-
ation and apoptosis, and has immunomodulatory effects.
10
In
these ways, fermentable carbohydrates delivered to the colon
have potential anticarcinogenic and anti-inammatory actions.
13
Restriction of FODMAPs delivered to the colon to reduce gas
production, subsequent luminal distension and GI symptoms
might consequently have adverse effects on colonic health.
The present study aimed to address the hypothesis that a low
FODMAP diet recommended for reduction of IBS symptoms will
have adverse effects on colonic luminal microenvironment. This
was investigated by comparing the effects of a low FODMAP diet
with those of a FODMAP content of a typical Australian diet on
faecal microbiota and biomarkers related to colonic health.
Additional comparison with faecal indices while subjects con-
sumed their own diet was also performed. The bacteria targeted
were chosen on the basis of being avid butyrate-producers with
anti-inammatory association for some, traditional prebiotic bac-
teria and representatives of mucus-associated bacteria that have
putative health-promoting or detrimental effects.
914
Subjects
studied were participating in a randomised controlled efcacy trial
of the two diets where almost all food was provided and included
patients with IBS and healthy subjects.
6
METHODS
Participants
The study participants have been previously described in detail.
6
Briey, patients with IBS as dened by Rome III criteria
6
and
healthy controls were recruited via advertisements and word of
mouth. Exclusion criteria comprised coeliac disease, previous
abdominal surgery, comorbid conditions such as diabetes, and
inability to understand English. No participant had previously
visited a dietitian for management of GI symptoms, and had not
used antibiotics or probiotics for 2 weeks prior to study com-
mencement. Fibre supplements, laxatives and antidiarrhoeal
medications were not taken during the trial.
Study protocol
The study protocol has also been recently described in detail.
6
Briey, for 1 week, participants recorded their habitual dietary
intake and a 5-day faecal sample was collected (as outlined below).
Participants were then randomised according to a computer-
generated order to receive 21 days of a diet low in FODMAPs or
21 days of a diet containing FODMAP content of a typical
Australian diet. Participants were blinded to the diets and almost
all food was provided.
6
After this 21-day diet, each participant
entered a washout period of at least 21 days in which they
resumed their usual diet and then crossed over to the alternate
diet. From day 3 to day 7 of the habitual diet and day 17 to day 21
of interventional diets, participants collected all faeces passed.
Just prior to the faecal collection (morning of day 3 of habitual
and day 17 of interventional diets), participants swallowed a
capsule containing 24 radiopaque markers (Sitzmarks, Konsyl
Pharmaceuticals, Maryland, USA). The time and date of capsule
ingestion was noted. Participants were instructed to collect each
stool in a supplied plastic container and to avoid urine contamin-
ation. The containers were sealed and immediately stored in a
portable freezer (Waeco Pacic, Queensland, Australia). Each con-
tainer was marked with the date and time of stool passage. The
freezers were delivered to the laboratory within the week follow-
ing collection. Stools were X-rayed and radiopaque markers
counted to determine whole gut transit time (WGTT) based on
time of stool passage.
All participants gave written informed consent prior to study
commencement. The study protocol was approved by the Eastern
Health and Monash University Human Research and Ethics
Committees. The protocol was registered with the Australian New
Zealand Clinical Trials Registry (ACTRN12612001185853).
Interventional diets
Participants were supplied with three main meals and three
snacks daily as previously described.
6
The provided food was
free of charge and delivered to participants homes weekly. All
food consumed was recorded in diaries; dietary adherence was
based on these records.
The nutritional contents of the interventional diets were ana-
lysed using the Foodworks program (Xyris Software Pty Ltd;
Brisbane, Queensland, Australia) except for FODMAPs, which
were analysed using high performance liquid chromatography
and enzymatic assays.
15 16
The interventional diets differed
only in FODMAP-content6 as shown in table 1. Matching of
the diets for total bre and resistant star ch was achiev ed adding
psyllium and Hi-Maize 220 (Nat ional Starch and Chemical
Table 1 The mean daily nutrition information of provided low and
typical Australian FODMAP diets
Per day Typical Australian diet Low FODMAP diet p Value
Energy (MJ) 8.17 (7.378.97) 8.17 (7.099.24) NS
Protein (g) 96.1 (84.7107) 98.1 (83.7113) NS
Fat (g) 71.6 (49.493.8) 74.4 (51.997.0) NS
Total carbohydrate (g) 219 (180259) 215 (181249) NS
Sugars (g) 120 (103137) 122 (106139) NS
Starch (g) 94.0 (52.8135) 95.4 (59.7131) NS
Total dietary fibre* (g) 29.7 (23.935.7) 30.4 (24.236.5) NS
Fibre (g) 25.9 (21.330.6) 23.4 (18.728.2) NS
Resistant starch (g) 3.74 (1.855.63) 6.93 (3.5610.3) NS
Total FODMAPs (g) 23.7 (16.930.6) 3.05 (1.864.25) <0.001
Oligosaccharides (g) 5.49 (2.348.65) 1.57 (0.472.66) 0.009
Polyols (g) 4.21 (2.575.85) 0.20 (0.040.44) 0.002
Lactose (g) 1.35 (0.202.49) 0.05 (0.010.10) 0.033§
Fructose in excess
of glucose (g)
12.7 (8.06
17.3) 1.24 (0.412.07) 0.001
Diets were matched for all nutrients except daily FODMAPs, indicated in bold (paired
t test).
*Total dietary fibre comprises fibre and resistant starch.
The low FODMAP diet was supplemented with a daily average of 3 g psyllium.
The low FODMAP diet was supplemented with a daily average of 5 g Hi-Maize 220
(National Starch and Chemical Company; Bridgewater, New Jersey, USA).
§While there is a significant difference in lactose, 5 g lactose per sitting is considered
well absorbed and tolerated in majority of people
18
.
FODMAP, Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols;
NS, not significant.
Gut microbiota
94 Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264
Co mpany, New Jersey, USA), r espectiv ely.
6
For the typical Austr alian
diet, 4.4 g oligosaccharides, 2.6 g polyols and 23.7 g total
FODMAP s were consumed daily as guided by the Monash
Complete Nutritional A ssessment Q ues tionnaire.
17
The lo w
FODMAP diet aimed to keep oligosa ccharide, fructose in excess of
glucose and polyol content <0.5 g per sitting.
3
Average daily intake
was estima ted 1.6 g oligosaccharides, 0.2 g polyols and 3.1 g total
FODMAP s. Both diets wer e lo w in lactose (<5 g per sitting).
18
Faecal assessment
On delivery to the laboratory, the 5-day faecal samples were
defrosted, pooled and mixed, then transferred into small speci-
men containers. Samples were packed on dry ice and delivered
to the Commonwealth Scientic and Industrial Research
Organisation Animal, Food and Health Sciences (Adelaide,
South Australia), where they were thawed at 4°C, then trans-
ferred to an anaerobic chamber and aliquoted for further ana-
lysis. All samples were stored at 20°C until analysed for SCFA
and bacteria abundances. Commonwealth Scientic and
Industrial Research Organisation investigators were blinded to
the treatments, but not the patient cohorts.
Faecal contents were analysed in duplicate for SCFA by gas
chromatography and pH, as described previously.
19
Concentrations of the total SCFA (sum of SCFA) and individual
SCFA including branched-chain fatty acids (BCFA) were reported
as mmol/g of faecal matter.
DNA was extracted from 0.25 g faecal matter using a
repeat-bead-beating plus column method.
20
Total bacteria as
well as butyrate-producing bacteria Clostridium cluster IV
(Clostridium leptum group) including Faecalibacterium prausnit-
zii and Clostridium cluster XIVa (Clostridium coccoides group)
and Roseburia spp, prebiotic bacteria (Lactobacilli and
Bidobacteria spp), and mucus-degrading bacteria (Akkermansia
muciniphila, Ruminococcus gnavus and Ruminococcus torques)
were analysed. These bacteria were chosen for analysis to specif-
ically examine the role of dietary FODMAPs on bacteria
thought to be markers of inammation and bacteria traditionally
thought to be good markers of prebiotic effects.
Detailed methodology of the primers and optimised quantita-
tive real-time PCR conditions used are summarised in online
supplement 1 in addition to microbial diversity and lactate and
succinate.
Comparison of microbiota with symptom response
In order to assess whether patterns of microbiota predicted differ-
ences in symptoms experienced during the two interventional
diets, IBS subjects were arbitrarily categorised as non-responders
or good responders as dened by mean overall symptom scores in
the last 14 days of the low FODMAP diet <10 mm or >20 mm
below those in the typical Australian diet, respectively.
6
Whole gut transit time
WGTT was calculated as previously described.
21
For the
purpose of WGTT analysis, patients with IBS were further sub-
classed as diarrhoea-predominant (IBS-D), constipation-
predominant (IBS-C), patients with IBS with existing diarrhoea
and constipation (IBS-M) and patients with IBS with neither
diarrhoea nor constipation (IBS-U).
Statistical analysis
Sample size estimations were calculated based on GI symptoms
which have been previously published.
6
The data from patients
with IBS and healthy subjects were examined separately and
pooled (given the similarity between the results in the two
groups). Subject age and body mass index were presented as
median (IQR). A p value 0.05 was considered statistically sig-
nicant for data describing participant demographics, WGTT,
faecal pH and lactate and succinate. Data of faecal character-
istics were parametric, except for bacterial abundance, which
were normalised by log
10
conversion before further analysis. All
raw faecal characteristic data were presented as mean (95% CI).
Differences of faecal characteristics between the interventional
diets were shown as a ratio of low FODMAP compared with
typical Australian diet and did not t a normal distribution.
Hence, changes in bacterial abundance and SCFA were com-
pared between individual diets by Wilcoxon matched-pairs
signed rank test with Bonferroni corrections. Habitual diet data
comparing participant groups were analysed by unpaired t test
with Bonferroni correction; p0.006 was considered statistically
signicant for SCFA observations, p0.005 for absolute bacter-
ial abundance and p0.006 for relative bacterial abundance
observations. Multivariate analysis of denaturing gradient gel
electrophoresis (DGGE)-banding patterns was performed using
the Primer 6+Permanova package (PRIMER-E Limited,
Plymouth, UK), with the assumption that each DGGE band
represents one phylotype. Data were analysed using a
Bray-Curtis similarity matrix on fourth root-transformed data.
Differences between diets on the basis of DGGE-banding pat-
terns were calculated with a one-way and pairwise permanova
analysis. All statistical tests, unless specied, were analysed with
GraphPad Prism V.6 and SPSS V.20 programs.
RESULTS
Participants
Thirty-eight participants (30 IBS and 8 healthy controls) com-
pleted the study. Of the six IBS subjects who ceased the typical
Table 2 Comparison of subject demographics and habitual diet
characteristics between IBS and healthy cohorts
IBS (n=27)
Healthy
controls (n=6) p Value
Demographics
Female* 21 (78%) 5 (83%) NS
Age (years) 43 (2954) 31 (2361) NS
Body mass index (kg/m
2
) 24 (2327) 24 (2329) NS
Habitual dietary intake
Energy (MJ) 9.1 (8.3 to 10) 8.3 (7.1 to 9.5) NS
Protein (g) 94.7 (84.3 to 105) 91.4 (72.3 to 110) NS
Fat ( g) 87.6 (76.9 to 98.3) 81.7 (63.2 to 100) NS
Carbohydrate (g) 236 (207 to 266) 204 (144 to 264) NS
Sugars (g) 110 (88.8 to 130) 93.4 (58.4 to 128) NS
Starch (g) 140 (124 to 157) 118 (76.8 to 160) NS
Fibre (g) 24.1 (21.2 to 27.0) 22.5 (17.6 to 27.3) NS
Total FODMAPs (g) 16.6 (14.2 to 18.9) 18.2 (11.9 to 24.9) NS
Oligosaccharides (g) 3.9 (3.3 to 4.4) 3.9 (3.2 to 4.7) NS
Polyols (g) 1.6 (1.2 to 2.1) 2.5 (1.1 to 4.0) NS
Lactose (g) 11.1 (8.7 to 13.5) 11.8 (6.1 to 17.4) NS
Fructose (g) 18.7 (14.1 to 23.3) 16.5 (7.1 to 25.9) NS
Glucose ( g) 24.0 (17.7 to 30.3) 22.6 (12.9 to 32.4) NS
Data are presented as mean (95% CI) and compared by unpaired t test except where
specified.
*n (percentage of total ); Fishers exact analysis used.
Median (IQR).
Total FODMAP content does not include fructose in excess of glucose which cannot
be estimated from Foodworks program.
FODMAP, Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols;
NS, not significant.
Gut microbiota
Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264 95
Australian diet early due to unbearable symptoms, four com-
pleted faecal collection prior to exiting the study (range 7
12 days). One IBS and two healthy subjects did not complete
faecal collection. Thus, data from 27 IBS and 6 healthy subjects
were included in analysis. As shown in table 2, the cohorts were
well matched for sex, age and body mass index. Their habitual
diets were also matched in nutrients including FODMAP
content (table 2). Dietary adherence during the interventional
diets was good with all participants adhering to the typical
Australian diet, and 81% of IBS and all healthy participants
adhering to the low FODMAP diet for at least 81% of the
interventions.
Faecal analysis during habitual diet
Faecal pH, lactate, succinate, SCFA and absolute and relative
bacterial abundance in IBS and healthy subjects during their
habitual diet are shown in table 3. Besides lower isobutyrate and
isovalerate concentrations in patients with IBS when compared
with healthy subjects, there were no differences in other mea-
sured indices. On the habitual diets, WGTT was signicantly
slower in healthy (67.1 (47.0 to 87.2) h) participants when
compared with IB S-D (31.9 (22.4 to 41.4) h; p=0.001) and
IBS-M subjects (40.6 (21.5 to 59.6) h; p=0.034) (see online
supplement 2).
Comparison of biochemical indices on habitual and
interventional diets
As there were few differences in faecal measures during the
habitual diet, IBS and healthy cohorts were combined. Faecal
pH was 0.2 units higher on the low FODMAP in comparison
with the habitual and typical Australian diets (p=0.008). No
differences were seen in total or specic faecal SCFA or succin-
ate between diets (table 4 and gure 1A). Only one participant
had complete data for faecal lactate, so could not be analysed.
Molar proportions of the major SCFA were also unchanged
(data not shown).
Absolute and relative abundance of bacteria are shown in
table 5. When analysed as absolute abundance, the low
FODMAP diet had a lower total bacterial load compared with
habitual and typical Australian diets (table 5 and gure 1B).
Furthermore, absolute abundance of the butyrate-producing
bacteria, the prebiotic bacteria, Bidobacteria spp and the
mucus-associated bacterium, A. muciniphila, was greater on the
typical Australian diet compared with the other two diets
(table 5 and gure 1B). In terms of relative abundance, the
typical Australian diet increased Clostridium cluster XIVa and A.
muciniphila in comparison with habitual and low FODMAP
diets, but decreased R. torques in comparison with the low
FODMAP diet (table 5 and gure 1C). Microbial diversity in
the Clostridium cluster XIV was greater in subjects on the low
FODMAP compared with the typical Australian diet and the
habitual diet (table 5). Similar patterns were seen when data
were separated into IBS and healthy cohorts.
Neither dietary changes nor the habitual diet pattern in abso-
lute and relative bacterial abundances predicted symptomatic
difference between the interventional diets in non-responders
and good responders (see online supplement 3).
Altering dietary FODMAPs did not affect WGTT in any
subject cohort, including specic IBS subtypes. The healthy sub-
jects had a slower WGTT when compared with IBS-D and
IBS-M subjects on all diets as well as IBS-C subjects during the
interventional diets (see online supplement 2). No correlation
between WGTT and the composition of the gut microbiota were
observed (data not shown).
DISCUSSION
The low FODMAP diet has good evidence of efcacy for
symptom management in patients with IBS.
6
However, as
FODMAPs, especially oligosaccharides, have shown positive
effects on the colonic microenvironment and microbiota in
healthy populations,
78
a low FODMAP diet might impact nega-
tively on colonic health. The present study investigated its
effects in 33 subjects compared with those of a carefully
matched diet representing the typical FODMAP intake in
Australia on markers linked to colonic health through the assess-
ment of WGTT, soluble luminal microenvironment and faecal
microbiota. Marked differences in absolute and relative bacterial
abundance and diversity, but not SCFA or transit were observed.
Table 3 Faecal pH, lactate, succinate, SCFA, absolute and relative
bacterial abundance and bacterial diversity on pooled 5-day
samples in IBS and healthy subjects during their habitual diet
IBS (n=27)
Healthy control
(n=6) p Value
pH 7.19 (7.077.31) 7.17 (6.637.72) 0.916
Lactate (g/100 g)* 0.02 (0.020.03) 0.02 (00.04) 0.375
Succinate (g/100 g)* 0.03 (0.020.03) 0.04 (0.020.06) 0.063
SCFA concentration (mmol/g)
Total SCFA 81.9 (72.391.5) 93.4 (58.6128) 0.334
Butyrate 15.6 (13.018.1) 18.9 (9.6128.3) 0.283
Propionate 15.8 (13.618.0) 17.6 (9.5325.6) 0.526
Acetate 42.5 (37.447.5) 44.7 (27.561.9) 0.715
Isobutyrate 1.92 (1.662.17) 3.10 (2.523.68) <0.001
Isovalerate 2.99 (2.563.43) 5.06 (3.926.19) <0.001
Valerate 2.28 (1.732.83) 3.70 (1.625.78) 0.044
Caproate 0.95 (0.581.32) 0.46 (0.121.04) 0.175
Absolute abundance (Log
10
copies of 16S rRNA gene/g)
Total bacteria 9.85 (9.729.98) 9.82 (9.6110.0) 0.861
Clostridium cluster IV 8.40 (8.208.59) 8.37 (7.978.76) 0.892
Faecalibacterium
prausnitzii
7.86 (7.688.05) 7.76 (7.128.39) 0.643
Clostridium cluster XIVa 8.26 (8.118.41) 8.04 (7.668.41) 0.193
7.64 (7.467.83) 7.50 (6.908.10) 0.518
Lactobacilli 6.27 (6.036.51) 5.94 (5.496.39) 0.219
Bifidobacteria 7.61 (7.377.86) 8.07 (7.558.58) 0.104
Akkermansia
muciniphila
4.07 (3.424.72) 4.50 (2.536.47) 0.571
Ruminococcus gnavus 7.20 (7.067.34) 6.96 (6.707.22) 0.129
Ruminococcus torques 6.09 (5.836.34) 6.74 (6.377.11) 0.025
Relative abundance (percentage of total bacteria)
Clostridium cluster IV 4.05 (3.344.77) 3.73 (2.395.07) 0.687
F. prausnitzii 1.31 (0.891.74) 1.18 (0.192.16) 0.778
Clostridium cluster XIVa 2.81 (2.403.22) 1.82 (0.972.67) 0.037
Roseburia 0.82 (0.571.06) 0.67 (0.131.22) 0.609
Lactobacilli 0.07 (0.010.13) 0.02 (00.03) 0.412
Bifidobacteria 1.33 (0.532.13) 2.18 (0.483.87) 0.348
A. muciniphila 0.01 (0
0.02) 0.01 (00.03) 0.756
R. gnavus 0.30 (0.200.40) 0.16 (0.040.28) 0.204
R. torques 0.03 (0.010.06) 0.12 (0.010.23) 0.008
Diversity (Shannon index)
Clostridium cluster XIV 1.83 (1.671.98) 1.64 (1.351.93) 0.310
Differences in cohorts were analysed by unpaired t test. Statistically significant
differences are shown in bold based upon p0.05 for pH, lactate and succinate,
p0.006 for SCFA concentrations, p0.005 for absolute and p0.006 for relative
bacterial abundance after Bonferroni correction.
*Due to difficulties in analysis, for lactate, IBS n=8 and healthy controls n=2.
Due to difficulties in analysis, for caproate, IBS n=18 and healthy controls n=5.
SCFA, short-chain fatty acid.
Gut microbiota
96 Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264
Comparisons with data during the participants habitual diet
were also made.
Colonic luminal concentrations of SCFA are of major import-
ance to gut health given their role in secretion, absorption,
motility and epithelial health. Because they are products of bac-
terial fermentation, a change in the delivery of fermentable sub-
strates to the colon is anticipated to alter the concentrations and
output of faecal SCFA. The low FODMAP diet reduced total
bacterial abundance in the faeces by an average 47% in compari-
son with the typical Australian diet, which in turn could pos-
sibly lower SCFA production. However, faecal SCFA
concentration was unaffected by the FODMAP content of the
diet, although faecal pH was higher on the low FODMAP diet.
This apparently paradoxical situation requires explanation.
While SCFAs are the major anions in the large bowel, other bac-
terial metabolites not measured or alterations in protein catabol-
ism may have contributed to the lower faecal pH associated
with FODMAP intake. The higher average resistant starch
content of the low FODMAP compared with that of the typical
Australian diet (table 1) might have compensated for the lower
FODMAP content as suggested by an animal trial comparing
resistant starch with fructo-oligosaccharides (FOS).
22
However,
the difference in resistant starch consumed in the present study
was small (3.2 g/d) and all previous studies have shown that at
least 16 g/d is required to alter faecal SCFA concentration, but
only when combined with wheat bran.
2224
Changes in colonic
transit will inuence faecal SCFA excretion, but WGTT was
similar in each dietary period. This nding is consistent with
previous data indicating that non-fermented or poorly fermen-
ted dietary bres are more effective faecal bulking agents and so
have a greater effect on hastening transit than readily fermented
carbohydrates.
2426
Although the methodology used measures
whole gut transit, it is likely that this reects large bowel transit
as this is the longest duration. Indeed, faecal weight was not
altered by FODMAP ingestion,
6
which might have been
expected by such a reduction in total bacterial abundance.
Supplementation of bre and resistant starch to the low
FODMAP diet may have concealed the expected change. The
most likely explanation for the apparent paradox is, because
FODMAPs are fermented in the proximal colon, that faecal
concentrations of SCFA are poor markers of colonic fermenta-
tion. It is also known that more than 95% of SCFAs are rapidly
absorbed and metabolised.
12
It is likely that changes in the structure of the microbiome
will translate into functional changes, although the nature of
such a relationship remains undened. The interventional diets
were associated with several differences in faecal microbiota.
Absolute abundances overall and of butyrate and prebiotic bac-
teria were less in association with the low FODMAP diet. This
is not surprising as these bacteria metabolise carbohydrates,
and a reduction of such substrates should lead to reduced pro-
liferation non-specically. Of the mucus-degrading bacterial
species, R. gnavus and A. muciniphila were reduced in total
abundance. As total bacterial abundance was altered on the
interventional diets, the effects of the diets on relative abun-
dance of specic bacteria were of more importance. Three bac-
terial groups of putative functional importance were targeted.
First, Clostridium cluster XIVa showed a sevenfold difference
between the two diets and this wide difference was observed in
all participants (IBS or healthy). This observation is consistent
with those in animal and human studies showing increased
Clostridium cluster XIVa in faeces and digesta after consump-
tion of oligosaccharides, or foods containing FODMAPs
(wheat bran).
92728
Second, traditionally prebiotic bacteria, namely
Bidobacterium spp, was similar between the two diets. The
only previous study to investigate prebiotic bacteria in associ-
ation with a low FODMAP diet identi ed a difference in abso-
lute and relative abundance of faecal Bidobacterium spp in
patients with IB S compared with those in a parallel UK popula-
tion consuming their habitual diet.
4
One possible explanation
for this discrepancy might be that the habitual diet in the UK
population contained a higher amount of galacto-oligosacchar-
ides (GOS) (mean (95% CI) 2.0 (1.4 to 2.5) g/d) and total oligo-
saccharides than provided by the typical Australian (GOS 1.01
(0.09 to 1.94) g/d) and habitual diets (GOS 0.76 (0.55 to 0.96)
g/d) of this Australian cohort. As oligosaccharides (including
GOS) are thought to inuence faecal concentrations of
Bidobacterium spp,
89
the greater decline from the habitual UK
to the low FODMAP diet may have been responsible for the
altered relative abundance in the UK subjects.
The third bacterial group studied was mucus-degrading bac-
teria, specically A. muciniphila and two Ruminococcus spp.
Simplistically, such bacteria are able to adhere to mucus and
feed off glycans and mucin proteins as part of the mucus
secreted by the gut epithelium.
29
Extensive degradation of the
mucous layer might be detrimental by impairing gut barrier
function. On the other hand, such foraging bacteria may
provide substrates for other bacteria important for development
of a healthy mucus-associated microbiota.
30
The diets were asso-
ciated with marked differences in the relative abundance of
A. muciniphila, (lower in the low FODMAP arm) and R. torques
(higher in the low FODMAP arm). The pattern observed was
similar as the difference seen in patients with IBD compared
with controls.
31 32
Similarly in mice
33
and rats inoculated with
human microbiota,
30
ingestion of oligosaccharides increase the
excretion of A. muciniphila. However, the mechanism is uncer-
tain as oligosaccharides do not directly promote the growth of
A. muciniphila in vitro.
32
Faecal abundance appears to reect
distal colonic mucosal abundance,
32
but whether it reects
mucus-degrading microbiota in the proximal colon is uncertain
Table 4 Faecal pH, succinate, total and specific SCFA (mmol/g) on
pooled 5-day faecal samples after following a habitual diet for
5 days and low FODMAP and typical Australian diets for 1721 days
in cross-over trial (n=33)
Measure Australian diet Low FODMAP diet p Value Habitual diet
pH 7.16 (7.027.30) 7.37*(7.237.51) 0.001 7.18 (7.077.31)
Succinate 0.03 (0.020.04) 0.03 (0.020.03) 0.178 0.03 (0.030.04)
Total SCFA 74.7 (65.983.4) 77.6 (68.886.5) 0.208 84.0 (74.893.2)
Butyrate 14.0 (11.816.2) 13.5 (11.315.7) 0.672 16.2 (13.718.6)
Propionate 14.4 (12.416.4) 15.2 (13.416.9) 0.145 16.2 (14.018.2)
Acetate 38.6 (34.143.1) 40.9 (36.145.6) 0.126 42.9 (38.247.6)
Isobutyrate 2.01 (1.662.37) 2.07 (1.692.45) 0.836 2.13 (1.862.41)
Isovalerate 3.15 (2.523.78) 3.22 (2.543.91) 0.857 3.37 (2.893.85)
Valerate 2.25 (1.822.67) 2.29 (1.902.69) 0.974 2.54 (1.973.10)
Caproate 1.03 (0.641.42) 1.13 (0.741.52) 0.454 1.20 (0.851.55)
Interventional diets were analysed by Wilcoxon matched-pairs signed rank test.
Statistically significant differences are shown in bold and based upon p0.05 for
faecal pH and p<0.006 for SCFA concentrations after Bonferroni correction.
Differences between habitual diet and interventional diets are indicated with an
asterisk.
*p=0.004 compared with habitual diet; Wilcoxon matched-pairs signed rank test.
Due to difficulties in analysis for succinate, n=18.
Due to difficulties in analysis for caproate, n=15.
FODMAP, Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols;
SCFA, short-chain fatty acid.
Gut microbiota
Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264 97
especially when caecal abundance of A. muciniphila was
reduced in association with FOS-induced increase in faecal
excretion of A. muciniphila in rodents.
30
Most evidence would
suggest that mucus-associated A. muciniphila have favourable
effects, perhaps via the provision of substrates such as acetate
and propionate for the support of a healthy consortium of bac-
teria adjacent to the epithelium.
14
The study of the effect of the
low FODMAP diet on mucus-degrading microbiota in the unin-
amed proximal and distal colon is required to resolve this
dilemma.
The diets differing in FODMAP content were also associated
with differences in the diversity of a cluster of bacteria including
many butyrate-producers, with greater diversity on the low
FODMAP diet. Reduced diversity is a common nding in dis-
eased colons, particular in association with IBD, where diversity
is inversely proportional to the degree of intestinal inamma-
tion.
34
However, the focus was specically on the Clostridium
cluster XIVa, which includes a large number of butyrate-
producing bacteria. The abundance of this group (Clostridium
cluster XIVa) declined signicantly on the low FODMAP diet in
IBS and healthy subjects. These two ndings together may rep-
resent an alteration in dynamics of this cluster of bacteria from
a cluster with fewer and more dominant species to one with
more but less dominant species on the low FODMAP diet.
However, functional and health signicances cannot be attribu-
ted to this difference in diversity at the present time.
The key question regarding the differences in microbiota
between diets that vary in their FODMAP intake is what is
increased and what is decreased. The characterisation of faecal
microbiota in the same participants while taking their habitual
diet provided that opportunity. As anticipated, bacterial abun-
dance was reduced in association with the low FODMAP diet.
However, the marked changes in relative abundance of
Clostridium cluster XIVa and A. municiphila reected an increase
Figure 1 Comparison of faecal indices with the two interventional diets in subjects with IBS and healthy subjects. (A) Changes in pH, total and
major short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs); (B) total and specic absolute bacterial abundance; and (C) relative
bacterial abundance. All data are presented as a ratio of low Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols (FODMAP)
to typical Australian diet and analysed by Wilcoxon matched-pairs signed rank test. Statistically signicant differences between the diets are
indicated with an asterisk based upon p0.05 for faecal pH, p0.006 for SCFA concentrations p0.005 for absolute and p0.006 for relative
bacterial abundance after Bonferroni correction.
Gut microbiota
98 Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264
in association with the Australian diet rather than a decrease in
the low FODMAP diet. This could be arguably described as a
prebiotic effect of the former diet. It is also reasonable to postu-
late that such a difference resided in the modest differences in
oligosaccharide intake in the typical Australian diet compared
with the habitual diet (approximately 1.6 g), although these two
indices were measured using different methods. In concert with
more oligosaccharides in the typical Australian than habitual diet,
there was a small increase in GI symptoms.
6
Hence, the low
FODMAP diet reduced absolute abundance of faecal bacteria,
but did not have an antiprebiotic effect.
The present study was not powered to compare faecal micro-
biota and biochemical indices in healthy subjects with those
who have IBS. However, similar trends in microbiota and SCFA
concentrations were noted. The only exceptions were the higher
faecal concentrations of the BCFA. BCFAs are products of
protein degradation, fermented increasingly through progression
to the distal colon,
35
and associated with increased genotoxicity
and possibly less cytotoxicity.
35
Reasons for differences in the
faecal BCFA concentrations, such as differences in microbiota
associated with protein fermentation, were not specically inves-
tigated. However, dietary components with potential to increase
faecal BCFAs, such as protein and calcium, which are thought
to alter genotoxicity and cytotoxicity, respectively,
36 37
were
similar between subject groups. Altering the dietary FODMAP
content showed a similar lack of response in SCFAs across the
two cohorts.
Post hoc analyses of faecal microbiota were performed to gain
some insight as to whether changes in the microbiota might
predict clinical response in patients with IBS (see online supple-
ment 3). No differences were observed between non-responders
and good responders indicating that the symptoms and micro-
biota were probably not directly associated in response to diet.
Similarly, faecal content of SCFA and BCFA were not associated
with response (data not shown).
In conclusion, this study is the rst randomised controlled
trial to compare faecal soluble milieu and microbiota in sub-
jects with IBS while following two controlled diets differing in
their FODMAP content in a cross-over design. There was a
higher faecal pH, but the concentrations of faecal SCFAs were
not different. In contrast, marked changes in the microbiota
were found. The low FODMAP diet was associated with lower
absolute abundance of total bacteria, butyrate-producing bac-
teria, prebiotic bacteria and A. muciniphila and R. gnavus.
Marked lower relative abundances of Clostridium cluster XIVa
and A. muciniphila,andasignicantly higher abundance of
R. torques were also observed. Finally, bacterial taxonomic diver-
sity of a large cluster of primarily butyrate-producers was greater
on the low FODMAP diet. Comparison with faecal microbiota
on habitual diet indicated that the low FODMAP intake was
associated with reduced absolute abundance of bacteria, but the
higher FODMAP intake associated with the typical Australian
diet showed evidence of specic stimulation of the growth of
bacterial groups with putative health benets. The functional sig-
nicance and health implications of such changes might lead to
caution about reducing FODMAP intake in the longer term.
Liberalising FODMAP restriction to the level of adequate
symptom control should be exercised. The low FODMAP diet
should not be recommended for asymptomatic populations.
Acknowledgements The authors thank Gina Dimitrakopoulos and Debbie King
(Monash University) for their assistance with food preparation and packaging, Kelly
Liels, Ourania Rosella and Rosemary Rose (Monash University) for analysis of
FODMAP content of meals, Simone Peters and Chu Kion Yao (Monash University) for
statistical analysis, and Jennifer Giles (CSIRO) for molecular microbiological analysis.
Contributors Study concept and design: EPH, SJS, PRG, JGM; recruitment, enrolment
and assessment of participants: EPH, JGM; acquisition of data: EPH; analysis and
interpretation of data: EPH, CTC, ARB, PRG; study supervision: SJS, PRG, JGM; drafting
of the manuscript: EPH, CTC, ARB, PRG; approval of nal draft: all authors.
Funding This study was supported by the National Health and Medical Research
Council (NHMRC) of Australia and the Les and Eva Erdi Foundation. EPH was
Table 5 Absolute and relative bacterial abundance and bacterial diversity on pooled faecal samples after following a habitual diet for 5 days
and low FODMAP and typical Australian diets for 1721 days in cross-over trial (n=33)
Measure Bacteria Australian diet Low FODMAP diet p Value Habitual diet
Absolute abundance (Log
10
copies of 16S rRNA gene/g) Total bacteria 9.83 (9.729.93) 9.63*(9.539.73) <0. 001 9.85 (9.739.96)
Clostridium cluster IV 8.33 (8.158.52) 8.05*(7.888.23) <0. 001 8.39 (8.238.56)
Faecalibacterium prausnitzii 7.72 (7.497.95) 7.45*(7.257.65) <0. 001 7.84 (7.678.01)
Clostridium cluster XIVa 9.05*(8.939.16) 8.03 (7.918.15) <0.001 8.22 (8.09 8.36)
Roseburia 7.72 (7.597.85) 7.49 (7.347.63) <0.001 7.62 (7.457.79)
Lactobacilli 6.35 (6.206.50) 6.08 (5.916.24) 0.003 6.21 (6.006.42)
Bifidobacteria 7.71 (7.53
7.88) 7.30*(7.117.50) <0.001 7.70 (7.487.91)
Akkermansia muciniphila 5.46*(4.886.04) 4.29 (3.584.99) <0.001 4.29 (3.674.92)
Ruminococcus gnavus 7.26 (7.147.37) 7.10 (6.967.25) 0.002 7.16 (7.047.28)
Ruminococcus torques 6.08 (5.856.31) 6.23 (6.076.39) 0.140 6.20 (5.976.44)
Relative abundance (percentage of total bacteria) Clostridium cluster IV 4.00 (3.214.71) 3.32 (2.703.94) 0.108 3.99 (3.394.60)
F. prausnitzii 1.11 (0.821.40) 0.95 (0.691.22) 0.108 1.29 (0.921.66)
Clostridium cluster XIVa 18.1*(15.420.8) 2.72 (2.333.12) <0.001 2.63 (2.26 3.01)
Roseburia 0.85 (0.5851.11) 0.82 (0.680.96) 0.153 0.79 (0.581.00)
Lactobacilli 0.05 (0.030.06) 0.04 (0.030.05) 0.634 0.06 (0.010.11)
Bifidobacteria 1.33 (0.741.92) 0.87 (0.471.27) 0.028 1.48 (0.792.18)
A. muciniphila 0.10*(0.030.16) 0.02 (0.010.03) <0.001 0.01 (00.02)
R. gnavus 0.37 (0.230.50) 0.41 (0.270.53) 0.480 0.27 (0.190.36)
R. torques 0.04 (0.020.06) 0.06 (0.040.09) 0.001 0.05 (0.020.08)
Diversity (Shannon index) Clostridium cluster XIV 1.47 (1.391.55) 1.79 (1.701.89) <0.001 1.60 (1.461.73)
Interventional diets were analysed by Wilcoxon matched-pairs signed rank test. Statistically significant differences are shown in bold and based upon p0.05 for bacterial diversity,
p0.005 for absolute and p0.006 for relative bacterial abundance after Bonferroni correction. Differences between habitual diet and interventional diets are indicated with an asterisk.
*p<0.001 compared with habitual diet; Wilcoxon matched-pairs signed rank test.Due to difficulties in microbial analysis for A. muciniphila, three IBS subjects could not be included;
n=30.
p<0.05 compared with habitual diet; pairwise permanova test.
FODMAP, Fermentable Oligosaccharides, Disaccharides, Monosaccharides And Polyols.
Gut microbiota
Halmos EP, et al. Gut 2015;64:93100. doi:10.1136/gutjnl-2014-307264 99
supported by a scholarship from the Faculty of Medicine, Nursing and Health
Sciences, Monash University.
Competing interests SJS has published a book on food intolerances and several
cookbooks related to the topic of the manuscript. PRG has published a book on food
intolerances. There were no conicts of interest to declare for EPH, CTC, ARB, JGM.
Patient consent Obtained.
Ethics approval Eastern Health and Monash University Human Research and
Ethics Committees.
Provenance and peer review Not commissioned; externally peer reviewed.
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... The factors that exacerbate IBS include changes in gut motility and sensitivity, changes in the intestinal flora, dysregulation of the gut-brain axis, dietary factors, socio-psychological and genetic factors, and stress [2][3][4][5]. Dietary factors may indirectly affect the intestinal flora and can be modified by the individual patient [6]. Modifying dietary factors alone can contribute to a significant improvement in the patient's condition. ...
... Due to their small molecular size, they exert an osmotic effect and draw fluid through to the large bowel. Further, they are easily fermented by intestinal bacteria, leading to the production of gas and other symptoms of IBS [6,9]. To alleviate these symptoms, a low-FODMAP diet is recommended [10]. ...
... The mannitol intake was significantly different between the 2 groups (P = 0.013), with no significant difference between men and women. The fructan intake in the IBS group was 4. 6 while that in the healthy group was 4.3 ± 2.5 g/day (P = 0.014), with significant differences only among men (IBS group vs. healthy group: 4.6 vs. 5.0 g/day, P = 0.026). ...
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BACKGROUND/OBJECTIVES The dietary intake of foods with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) is known to adversely affect patients with irritable bowel syndrome (IBS). However, the effects of FODMAP have been studied predominantly among Western populations. This study aimed to identify foods high in FODMAP content which form a part of the Korean adult diet and obtain basic data for the preparation of IBS guidelines. SUBJECTS/METHODS An online survey of 1,000 adults from the general population in the age group of 20 to 40 years was performed. Data from 787 participants (men, 386; women, 401) were analyzed. The general characteristics of the participants, health status, IBS diagnosis using the Rome III diagnostic criteria, semi-quantitative food frequency questionnaire findings, and food items causing symptoms were analyzed. RESULTS Overall, 169 participants (21.5%) had IBS. The contribution of the FODMAP nutrients in both IBS and healthy groups was as follows: fructan > lactose > excess fructose > sorbitol > mannitol > galacto-oligosaccharides (GOS). The fructan intake was 4.6 ± 2.2 g/day and 4.3 ± 2.5 g/day in the IBS and healthy groups (P = 0.014), respectively. In the IBS group, the ratio of the intake of fructan to the total FODMAP intake was 39.5%, 29.8%, and 5.8% through onions, garlic, and bananas, respectively. CONCLUSIONS Fructan was the FODMAP nutrient most consumed by Korean adults. Therefore, given the difference in the dietary habits of each country’s population, the dietary guidelines for IBS should be country specific.
... Group C: ↑ BCFAs; ↑ Isovalerate and isobutyric. (Table 3) Three clinical trials [53][54][55] assessed the impact of LFD on IBS patients and measured BCFA production, while the last one provided a high-FODMAP diet [56] on IBS patients and measured the same fecal metabolites. Unfortunately, none of them measured inflammatory biomarkers. ...
... Halmos et al. [53] assessed the effects of an LFD versus a typical Australian diet on fecal biomarkers. This study included 33 participants (27 with IBS and 6 healthy controls). ...
... Volunteers followed two diets differing in FODMAP content (LFD contained 3.05 g, whereas the typical Australian diet contained 23.7 g of FODMAPs, respectively). At baseline, isovaleric and isobutyric levels were lower in IBS patients compared to controls, though no difference was noticed during the dietary intervention [53]. ...
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The literature about the association of branched short-chain fatty acids (BCFAs) and irritable bowel syndrome (IBS) is limited. BCFAs, the bacterial products of the catabolism of branched-chain amino acids, are proposed as markers for colonic protein fermentation. IBS is a gastrointestinal disorder characterized by low-grade inflammation and intestinal dysbiosis. The low-FODMAP diet (LFD) has increasingly been applied as first-line therapy for managing IBS symptoms, although it decreases the production of short-chain fatty acids (SCFA), well known for their anti-inflammatory action. In parallel, high protein consumption increases BCFAs. Protein fermentation alters the colonic microbiome through nitrogenous metabolites production, known for their detrimental effects on the intestinal barrier promoting inflammation. Purpose: This review aims to explore the role of BCFAs on gut inflammation in patients with IBS and the impact of LFD in BCFAs production. Methods: A literature search was carried out using a combination of terms in scientific databases. Results: The included studies have contradictory findings about how BCFAs affect the intestinal health of IBS patients. Conclusions: Although evidence suggests that BCFAs may play a protective role in gut inflammation, other metabolites of protein fermentation are associated with gut inflammation. Further research is needed in order to clarify how diet protein composition and, consequently, the BCFAs are implicated in IBS pathogenesis or in symptoms management with LFD+.
... However, attention should be paid to the timing of the diets and dosages. On the other hand, gluten-free and lactose-free diets have positive effects only on a case-by-case basis depending on additional factors that interfere with nutrient tolerance [23][24][25][26][27][28][29][30]. The results of selected clinical trials are shown in Table 2. Ingredients in elimonated and included products during these diets can affect the course of IBS. ...
... On the other hand, the intake of dietary fiber, particularly water-soluble fiber, which influences the density, volume, consistency of stools and the composition and functioning of the intestinal microbiota, is increased in a high-fiber diet [17]. However, the results of the studies conducted so far are inconclusive and insufficient to recommend a single diet for every person with IBS [23][24][25][26][27][28][29]31,32]. The effectiveness of diets and their impact on the course of IBS is presented in Table 3. Table 3. Types of diets used in IBS and their effectiveness. ...
... Therefore, once IBS symptoms have abated, the diet should be expanded according to tolerance. More studies are needed to confirm efficacy [17,[26][27][28]. ...
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Irritable Bowel Syndrome (IBS) is a chronic, recurrent functional disorder of the intestine diagnosed based on the Rome IV criteria. Individuals suffering from IBS often associate the severity of their symptoms with the food they consume, leading them to limit the variety of foods they eat and seek information that could help them determine the appropriate selection of dietary items. Clear nutritional recommendations have not been established thus far. NICE recommends a rational approach to nutrition and, if necessary, the short-term implementation of a low FODMAP diet. Currently, the FODMAP diet holds the greatest significance among IBS patients, although it does not yield positive results for everyone affected. Other unconventional diets adopted by individuals with IBS lack supporting research on their effectiveness and may additionally lead to a deterioration in nutritional status, as they often eliminate foods with high nutritional value. The role of physical activity also raises questions, as previous studies have shown its beneficial effects on the physical and mental well-being of every individual, and it can further help alleviate symptoms among people with IBS. Supplementation can be a supportive element in therapy. Attention is drawn to the use of probiotics, vitamin D, and psyllium husk/ispaghula. This review aims to analyze the existing scientific research to determine the impact of various food items, physical activity, and dietary supplementation with specific components through dietary supplements on the course of IBS.
... A comprehensive systematic review and meta-analysis on 12 trials including 772 patients investigated the effects of a low-FODMAP diet on IBS symptoms, showing a significant improvement of IBS severity, according to the IBS Severity Scoring System (IBS-SSS), in most studies and higher IBS-QoL scores in patients with the low-FODMAP diet versus controls [181]. Many studies have investigated the effect of diet in IBS patients and gut microbiota modifications related to some specific diet regimens and especially the effects of a low-FODMAP diet on the colonic microbiota composition [182][183][184]. A low-FODMAP diet was found to alter the composition of the gut microbiota by significantly reducing the levels of Bifidobacteria and decreasing the overall bacterial count [185,186]. ...
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Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder characterized by chronic abdominal pain and altered bowel habits. It can be subclassified in different subtypes according to the main clinical manifestation: constipation, diarrhea, mixed, and unclassified. Over the past decade, the role of gut microbiota in IBS has garnered significant attention in the scientific community. Emerging research spotlights the intricate involvement of microbiota dysbiosis in IBS pathogenesis. Studies have demonstrated reduced microbial diversity and stability and specific microbial alterations for each disease subgroup. Microbiota-targeted treatments, such as antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and even diet, offer exciting prospects for managing IBS. However, definitive conclusions are hindered by the heterogeneity of these studies. Further research should focus on elucidating the mechanisms, developing microbiome-based diagnostics, and enabling personalized therapies tailored to an individual’s microbiome profile. This review takes a deep dive into the microscopic world inhabiting our guts, and its implications for IBS. Our aim is to elucidate the complex interplay between gut microbiota and each IBS subtype, exploring novel microbiota-targeted treatments and providing a comprehensive overview of the current state of knowledge.
... After the carbohydrate restriction, the authors showed a decrease in luminal Bifidobacteria concentration and percentage [34]. Recent randomized controlled trials also reported that an LFD can cause Bifidobacteria levels to decrease [35,36]. ...
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Irritable bowel syndrome (IBS) plagues nearly a fifth of the general population. It is a chronic illness that can significantly lower quality of life (QoL) and work productivity. The relationship between diet and the functional gastrointestinal (GI) symptoms present in IBS is gaining more and more attention. In addition to being a factor in the pathophysiology of IBS, diet also has a significant impact on symptoms and overall well-being. Recent research has also shown that short-chain fermentable carbohydrates increase colonic gas production and small intestine water volume, which in turn causes functional GI symptoms in those with visceral hypersensitivity. This review article has consolidated various studies highlighting the association between certain foods and the pathophysiology of IBS. It has also talked about how restricting certain food items from the diet of affected individuals can relieve symptoms and in some cases can be more effective than pharmacotherapy. Although the low reduced fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet (LFD) is a well-known method of treating IBS symptoms, over a third of individuals do not benefit from it. This article has also discussed the effectiveness and applicability of the LFD compared to other dietary therapies for the long-term management of IBS.
... In the study by Martínez et al. (2015), alpha diversity was lower in the US cohort than in the Papua Guinea cohort, which could be a result of the lower fiber consumption in Western societies compared with non-Westernized populations. Likewise, it has been demonstrated that a diet with low concentrations of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) impacts the microbiota and reduces the total bacterial abundance of butyrateproducing Clostridium cluster, as well as mucus-associated Akkermansia muciniphila and fiber-degrading Ruminococcus torques (Halmos et al. 2015). An earlier study showed that Bifidobacterium was reduced in response to low FODMAP (Staudacher et al. 2012). ...
Book
Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. The mechanisms by which probiotics affect the host are based on one of two principles: i) directly, by interacting with specific targets, or ii) indirectly, by contributing to the ecological niche constructions of the microbiota. This thesis examined how probiotic bacteria interact with each other and with the host, and how production of probiotics can be manipulated to increase biological functionality, ultimately benefiting the host. Limosilactobacillus reuteri DSM 17938 is a well-documented probiotic strain, but the mechanisms by which it alleviates infantile colic, combats inflammation, and interacts with the immune system are not well understood. However, several features related to the bioactive properties of DSM 17938 may partly explain these interactions. The features in question are extracellular membrane vesicles (MV), exopolysaccharides (EPS), enzymes, and other metabolites. MV and EPS were evaluated in different models of host interactions, aimed at reflecting possible mechanisms of action in infantile colic. Multifunctionality among the MV was demonstrated and it was also shown that the amount and activity of bioactive components can be altered by optimizing production parameters. Further, a novel strain of Bifidobacterium longum subsp. longum was described and shown to be a potent fiber degrader, able to stimulate growth and bioactivity of DSM 17938 and its MV in vitro. Bifidobacteria and lactobacilli are important in ecological niches of the human gut and the interactions between these bacteria may be key to understanding how to fight inflammatory diseases and disorders using probiotics.
... For IBD patients, a low FODMAP diet has the potential to reduce symptoms and enhance the quality of life [57]. However, prolonged restriction might decrease beneficial gut bacteria, emphasizing the need for professional guidance [73]. ...
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... Prebiotics; consist of soybeans, inulin, unrefined wheat, raw oats, fructans, polydextrose, fructooligosaccharides, galactooligosaccharides, xylooligosaccharides, and arabinooligosaccharides (Pandey et al., 2015). Regardless of the specific bacteria, prebiotics have been reported to increase lactic acid bacteria and beneficial bacteria, and whole grain products have beneficial effects on the gut microbiota due to their high fiber content (Halmos et al., 2015). Fava et al. (2013) studied the effects of dietary fat content on the gut microbiota and found that a low-fat diet increased bifidobacteria density, resulting in a decrease in fasting glucose and total cholesterol. ...
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The modern medical education system has gradually evolved starting from 1910 incorporating the suggestions by Abraham Flexner, his public disclosure of the poor conditions at many medical schools provided a means to galvanize all the constituencies needed for reform to occur. He could say what other reformers could not, due to their links to the medical education community. But now we are again going back to a pre-Flexnerian state due to multiple reasons such as gradually diminishing importance of basic science subjects for the students, the decline in the number and quality of investigator initiated research among clinical researchers, lesser emphasis to bedside training by means of detailed clinical examination and making appropriate observation of signs to reach to a diagnosis rather than over reliance on the laboratory tests and radiological modalities for the diagnosis, poor exposure to basic clinical skills starting from college throughout residency and the trend of disrespect and absenteeism from both theoretical and clinical/practical classes. The attitude of students is just to complete their required attendance so that they are not barred from appearing in examinations. This de-Flexnerization trend and regression to pre-Flexnerian era standards, ideologies, structures, processes, and attitudes, are bound to beget pre-Flexnerian outcomes, for you get what you designed for.
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A diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) is often used to manage functional gastrointestinal symptoms in patients with irritable bowel syndrome (IBS), yet there is limited evidence of its efficacy, compared with a normal Western diet. We investigated the effects of a diet low in FODMAPs compared with an Australian diet, in a randomized, controlled, single-blind, cross-over trial of patients with IBS. In a study of 30 patients with IBS and 8 healthy individuals (controls, matched for demographics and diet), we collected dietary data from subjects for 1 habitual week. Participants were then randomly assigned to groups that received 21 days of either a diet low in FODMAPs or a typical Australian diet, followed by a washout period of at least 21 days, before crossing over to the alternate diet. Daily symptoms were rated using 0-100 mm visual analogue scale. Almost all food was provided during the interventional diet periods, with a goal of <0.5 g intake of FODMAPs per meal for the low-FODMAP diet. All stools were collected from days 17-21 and assessed for frequency, weight, water content, and King's Stool Chart (KSC) rating. Subjects with IBS had lower overall gastrointestinal symptoms scores (22.8; 95% confidence interval, 16.7-28.8 mm) while on a diet low in FODMAPs, compared with the Australian diet (44.9; 95% confidence interval, 36.6-53.1 mm; P<.001) and the subjects' habitual diet. Bloating, pain, and passage of wind were also reduced while IBS patients were on the low-FODMAP diet. Symptoms were minimal and unaltered by either diet among controls. Patients of all IBS subtypes had greater satisfaction with stool consistency while on the low-FODMAP diet, but diarrhea-predominant IBS was the only subtype with altered fecal frequency and KSC scores. In a controlled, cross-over study of patients with IBS, a diet low in FODMAPs effectively reduced functional gastrointestinal symptoms. This high-quality evidence supports its use as a first-line therapy. Clinical Trial number: ACTRN12612001185853.
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Preliminary studies indicate that dietary restriction of fermentable short-chain carbohydrates improves symptoms in irritable bowel syndrome (IBS). Prebiotic fructo-oligosaccharides and galacto-oligosaccharides stimulate colonic bifidobacteria. However, the effect of restricting fermentable short-chain carbohydrates on the gastrointestinal (GI) microbiota has never been examined. This randomized controlled trial aimed to investigate the effects of fermentable carbohydrate restriction on luminal microbiota, SCFA, and GI symptoms in patients with IBS. Patients with IBS were randomized to the intervention diet or habitual diet for 4 wk. The incidence and severity of symptoms and stool output were recorded for 7 d at baseline and follow-up. A stool sample was collected and analyzed for bacterial groups using fluorescent in situ hybridization. Of 41 patients randomized, 6 were withdrawn. At follow-up, there was lower intake of total short-chain fermentable carbohydrates in the intervention group compared with controls (P = 0.001). The total luminal bacteria at follow-up did not differ between groups; however, there were lower concentrations (P < 0.001) and proportions (P < 0.001) of bifidobacteria in the intervention group compared with controls when adjusted for baseline. In the intention-to-treat analysis, more patients in the intervention group reported adequate control of symptoms (13/19, 68%) compared with controls (5/22, 23%; P = 0.005). This randomized controlled trial demonstrated a reduction in concentration and proportion of luminal bifidobacteria after 4 wk of fermentable carbohydrate restriction. Although the intervention was effective in managing IBS symptoms, the implications of its effect on the GI microbiota are still to be determined.
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Dietary inclusion of fermentable carbohydrates (fCHO) is reported to reduce large intestinal formation of putatively toxic metabolites derived from fermentable proteins (fCP). However, the influence of diets high in fCP concentration on epithelial response and interaction with fCHO is still unclear. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP/low fCHO [14.5% crude protein (CP)/14.5% total dietary fiber (TDF)]; low fCP/high fCHO (14.8% CP/16.6% TDF); high fCP low fCHO (19.8% CP/14.5% TDF); and high fCP/high fCHO (20.1% CP/18.0% TDF) as dietary treatments. After 21-23 d, pigs were killed and colon digesta and tissue samples analyzed for indices of microbial ecology, tissue expression of genes for cell turnover, cytokines, mucus genes (MUC), and oxidative stress indices. Pig performance was unaffected by diet. fCP increased (P < 0.05) cell counts of clostridia in the Clostridium leptum group and total short and branched chain fatty acids, ammonia, putrescine, histamine, and spermidine concentrations, whereas high fCHO increased (P < 0.05) cell counts of clostridia in the C. leptum and C. coccoides groups, shifted the acetate to propionate ratio toward acetate (P < 0.05), and reduced ammonia and putrescine (P < 0.05). High dietary fCP increased (P < 0.05) expression of PCNA, IL1β, IL10, TGFβ, MUC1, MUC2, and MUC20, irrespective of fCHO concentration. The ratio of glutathione:glutathione disulfide was reduced (P < 0.05) by fCP and the expression of glutathione transferase was reduced by fCHO (P < 0.05). In conclusion, fermentable fiber ameliorates fermentable protein-induced changes in most measures of luminal microbial ecology but not the mucosal response in the large intestine of pigs.
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It is generally accepted that carbohydrate fermentation results in beneficial effects for the host because of the generation of short chain fatty acids, whereas protein fermentation is considered detrimental for the host's health. Protein fermentation mainly occurs in the distal colon, when carbohydrates get depleted and results in the production of potentially toxic metabolites such as ammonia, amines, phenols and sulfides. However, the effectivity of these metabolites has been established mainly in in vitro studies. In addition, some important bowel diseases such as colorectal cancer (CRC) and ulcerative colitis appear most often in the distal colon, which is the primary site of protein fermentation. Finally, epidemiological studies revealed that diets rich in meat are associated with the prevalence of CRC, as is the case in Western society. Importantly, meat intake not only increases fermentation of proteins but also induces increased intake of fat, heme and heterocyclic amines, which may also play a role in the development of CRC. Despite these indications, the relationship between gut health and protein fermentation has not been thoroughly investigated. In this review, the existing evidence about the potential toxicity of protein fermentation from in vitro animal and human studies will be summarized.
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Emerging evidence indicates that the consumption of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) may result in symptoms in some patients with irritable bowel syndrome (IBS). The present study aimed to determine whether a low FODMAP diet is effective for symptom control in patients with IBS and to compare its effects with those of standard dietary advice based on the UK National Institute for Health and Clinical Excellence (NICE) guidelines. Consecutive patients with IBS who attended a follow-up dietetic outpatient visit for dietary management of their symptoms were included. Questionnaires were completed for patients who received standard (n = 39) or low FODMAP dietary advice (n = 43). Data were recorded on symptom change and comparisons were made between groups. In total, more patients in the low FODMAP group reported satisfaction with their symptom response (76%) compared to the standard group (54%, P = 0.038). Composite symptom score data showed better overall symptom response in the low FODMAP group (86%) compared to the standard group (49%, P < 0.001). Significantly more patients in the low FODMAP group compared to the standard group reported improvements in bloating (low FODMAP 82% versus standard 49%, P = 0.002), abdominal pain (low FODMAP 85% versus standard 61%, P = 0.023) and flatulence (low FODMAP 87% versus standard 50%, P = 0.001). A low FODMAP diet appears to be more effective than standard dietary advice for symptom control in IBS.