The Impact of Probiotic Therapy on the Levels of Butyrate Acid in

Inflammatory Bowel Disease

Fauzi Yusuf

, Azzaki Abubaka

, Wah

uddin Wah

uddin

and Siti Adewiah

Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine University of Syiah Kuala/

Dr. Zainoel Abidin Centre Hospital, Banda Aceh, Indonesia

Department of Internal Medicine, Faculty of Medicine, Syiah Kuala University, Banda Aceh, Indonesia.

Keywords: IBD, Butyrate Acids, Probiotics

Abstract : Inflammatory bowel disease (IBD) is a term applied to a group of bowel disorders in which

inflammation is a major feature, it is widely accepted that these diseases have long been associated with

imbalances in mucosal levels of micro-flora-produced short-chain fatty acids such as butyrate. 10

Patients received a 2 –week probiotic treatment and 10 control patients received a placebo for the same

period. For the pre- and post-intervention assessments, stool samples were analysed for their level of

butyrate acid with gas chromatography. This study showed that the mean concentration of butyrate acids

in pre- and post- probiotic therapy was 6.49 ±2.64 versus 21.07 ±8.01 umol/g. Compared to the group

who received the placebo, the group who received the probiotic therapy showed a significant increase in

the level of butyrate acid ( P < 0.001). Future research should be done to study the effects of the therapy

with larger samples over longer periods.

1 INTRODUCTION

Ulcerative colitis (UC) and Crohn’s disease (CD)

are 2 of the primary types of Inflammatory Bowel

Disease (IBD) (Friedman S and Blumberg RS,

2010; Ng SC et al, 2017). There is a high incidence

of both UC and CD in Europe, England and North

America. Worldwide, the incidence of UC is

between 10 to 20 per 100,000 population per annum

with a prevalence of 50 to 100 per 100,000

population. There are many factors which can cause

IBD: however, at present, changes in the mikroflora

in the intestines is believed to be the primary factor

in the pathogenesis of IBD; such changes make it

possible that the supply of a beneficial nicro-

organism through changes/addition to/in the diet

could reduce the incidence of inflammation

(Olendzki BC et al, 2014).

A Probiotic is a living micro-organism which if

given in a sufficient quantity will bring health

benefits to the sufferer ( WHO, 2001). Lactobacillus

and bifidobacteria are probiotic anaerobic microbes

which produce lactic acid as a final metabolite from

fermentation of carbohydrates. The primary products

from the anaerobic microbial fermentation which are

found in the large intestine and which affect the

physiological condition of the large intestine are

short chain fatty acids (SCFA), namely acetate,

propionate and butyrate acids (Mattu B and

Chauhan A, 2013). A most important part of the

imbalances that develops in the composition of the

micro-biota is the significant decrease in the

digestive tract of microbiota coming from the

butyrate acid.

The decrease in the butyrate reflects the increase

in oxidation of the SCFA by colorectal mucosa

(Kelly D et al, 2005, Chen W et al ,2012). The

purpose of this study is to measure the levels of

butyrate acid in IBD patients, both before and after

they are given a probiotic treatment.

2 PATIENTS AND METHODS

The samples for this research were faeces from IBD

patients who were confirmed by colonoscopy and

who met the criteria for inclusion. The sample was

gathered by asking successive patients with IBD

whether they would agree to participate in the study.

Patients who met the criteria for inclusion were

asked to agree in writing to participate in the

research by signing an informed consent agreement

after they had been briefed on the purpose and the

nature of this research. The sample patients were

split into two groups, an intervention or treatment or

experimental group (IG.) and a control Group (CG):

Yusuf, F., Abubakar, A., Wahyuddin, . and Adewiyah, S.

The Impact of Probiotic Therapy on the Levels of Butyrate Acid in Inﬂammatory Bowel Disease.

DOI: 10.5220/0008791300810084

In Proceedings of the 2nd Syiah Kuala International Conference on Medicine and Health Sciences (SKIC-MHS 2018), pages 81-84

ISBN: 978-989-758-438-1

and the pre-treatment research samples (ie., the

faeces from the patients) were collected from both

groups to measure the level of butyrate acid in them.

Next the IG were given a probiotik treatment while

the CG were given a placebo for 2 (two) weeks:

After that the post-treatment faeces were collected

from the two groups for analysis of the butyrate

content, to see the effect of the treatment.

Criteria for Inclusion : 1). The patients is aged

between 18 and 65, either male or female ; 2) The

patient has Indonesian heritage as proven by her/his

KTP and, through interview, can provide a family

tree of three generations, namely the patient, her/his

parents and the four grandparents ; 3) The patient is

suffering from IBD as proven by a colonoscopy

examination and (s)he agrees to consume a probiotik

or a placebo for 2 (two) weeks and (s}he agrees to

provide her/his faeces for examination of the butirate

content; 4 )The patient agrees to be interviewed, is

co-operative and can communicate well, (s)he agrees

to provide specimens to be examined as material for

the study and for the results to be published; such

agreement to be confirmed by signing an informed

consent agreement.

Criteria for Exclusion : 1). The IBD patient

does not meet the requirements for examination of

faeces and colonoscopy ( for example (s)he is

suffering from a toxic megacolon, fulminan colitis,

perforated colon and/or other very serious condition

; 2) The patient has previously had antibiotic

therapy, corticosteroids, amino salisilate acid and/or

has used imunomodulators (Azatrioprin, 6-

merkaptopurin, siklosporin and/or metotreksat)

and/or therapy specifically for other intestinal

inflammation (inflicsimab, tocolizumab, filgrastim)

in the past three (3) months.

This study was an experimental study designed

to use case control with a two (2) group pre-test &

post-test design (before and after), the first group or

the intervention group (IG) are IBD patients who are

given the experimental treatment and the second or

control group (CG) are IBD patients who are given a

placebo. This design enables comparison between

the two groups and measurement of the differences

which have occurred as a result of the treatment. The

purpose of this study was to measure the

concentration of butirate acid in the faeces of IBD

patients before and after being given a probiotik for

three weeks and of a control group of IBD patients

after being given a placebo for the same period and

to compare the difference in butyrate acid content

between the two groups before and after the

treatment.

3 RESULTS

The age and gender characteristics and the butirate

acid content before and after treatment, of the 20

IBD patients from the Dr Zainoel Abidin Provincial

General Hospital in Banda Aceh who were the

subjects of this research, are set out in Table 1,

which follows:

Table 1; Gender, Age & Butyrate Acid Content of IBD

patients in IG and CG

Variable

Intervention

group

(% or SD)

Control group

(% or SD)

Sex

Male

Female

8 (80%)

2 (20%)

8 (80%)

Age group

(years)

≤ 30

31 – 40

41 – 50

≥ 50

3 (30%)

2 (20%)

3 (30%)

2 (20%)

4 (40%)

3 (30%)

2 (20%)

1 (10%)

Butyrate acid

level(umol/g)

Pre-treatment

Post-

treatment

6.49 ± 2.64

21.07 ± 8.01

19.66 ± 12.99

13.84 ± 12.76

Note: IG, IBD patients, got probiotic treatment; CG, IBD patients

got placebo treatment

To summarise the results: The level of butyrate

acid in the IG increased between the pre-treatment

and the post-treatment from 6 to 21 umol/g with an

increase in SD from 3 to 8 while for the CG the

change in level between the pre-test and the post-test

was actually a decrease from 20 to 14 umol/g while

the SD stayed at 13.

Table 2. Comparison butyrate acid’s level between two

group

Group

Paired

Sample

Mean

Differences

t-Test

value

Interventi

on group

Pre test-

post test

-14,58 -6,748 <

0,001

Control

group

Pre test-

post test

5,82 ,521 0,163

From the results in Table 2, it can be seen that

for the Intervention Group the average difference in

the level of butyrate acid from the pre-test to the

SKIC-MHS 2018 - The 2nd Syiah Kuala International Conference on Medicine and Health Sciences

post-test was -14,58. The negative value indicates

that the level of butyrate acid in the post-test was

higher than that in the pre-test. Furthermore, the

value of t-calculated from the paired sample t-test

for the level of butyrate acid for the Intervention

Group was -6,748 while the p-value was much

smaller at 0.001. Accordingly, it can be said that for

the Intervention Group the average level of butyrate

acid increased significantly between the pre-test and

the post-test. In other words, the treatment given

significantly increased the average level of butyrate

acid in the intestines of the treated patients.

Meanwhile the lrvel of butyrate acid in the Control

Group actually decreased by 5.82 between the tests

and the value of t-calculated from the paired sample

t-test for the level of butyrate acid for the Control

Group was 1.521 while the p-value was smaller at

0.163. Thus, in conclusion, the placebo did not

improve the level of butyrate acid in the CG

patients.

4 DISCUSSION

Butyrate acid is known to promote the benefits of

healthy intestines; it effectively stimulates the

proliferation of intestinal mucosal cells. The

lowering of the level of butyrate acid is believed to

contribute to getting IBD (

Prideaux L et al, 2012). The

purpose of this study was to measure the levels of

butyrate acid in IBD patients before and after getting

treatment with probiotics.

The data from this study showed that the

minimum levels of butyrate acid in the pre-tests

from the IG and the CG were 3,70 umol/g and 3,50

umol/g respectively,.while the maximums were 10

umol/g and 38,60 umol/g respectively and the

average levels were 6,49 umol/g and 19,66 umol/g

respectively.

Then for the Treatment Intervention Group (IG)

the post-test minimum, maximum and average levels

were 13,90 umol/g, 36,80 umol/g and 21,07 umol/g

while for the CG the average level actually

decreased to 13.84 umol/g.

Butyrate acid has important functions to protect

gastrointestinal health because it functions as a

primary source of energy for colonocytes, increases

the integrity of the epithel barrier and disrupts

inflammation (

Ringel Y et al, 2012). In their research,

Faujan et al, 2010. compared the levels of butyrate

acid in faeces from a normal population with those

from IBD patients and found that the butyrate acid

levels from the IBD patients were significantly

lower. Results from this study are in line with those

from Li et al, 2017. who also studied the relationship

between probiotik treatment and the level of butyrate

acid in faeces. From 81 patients studied there was a

significant increase in the level of butyrate acid in

the faeces after taking B. Bifidum and there was also

clinical improvement in the IBD patients verified by

colonoscopy.

The results from this study are similar with those

from a study by Takaishi et al who found that that

the concentration of butyrate and propionate acids in

the faeces of IBD patients was significantly lower

than that in a normal population (

Takaishi H et al,

2008). Vernia et al, 1988. reported that there was a

similar decrease of butyrate acid in UC patients. The

butyrate molecule is important for the remission of

colitis. Reduction in butyrate acid reflects an

increase in oxidation of SCFA by colorectal mucosa

(

Ishikawa H et al, 2011). The consumption of

probiotics can reduce inflammation and improve

health due to the production of SCFA in the large

intestine and can reduce the production of the

hydrogen peroxide radical. As well as that, the

benefits of probiotics for oxidative stress biomarkers

is possible because of the intestinal production of

butyrate acid. The results of this research are in

agreement with those from the study by Geinaert et

al in 2015 in Belgium which reported the increase

in butyrate acid content (of faeces) after 13 days

treatment with probiotics compared to a control

group. According to Geirnaert, the use of probiotics

and similar natural anti-microbial antagonists have

potential to be alternative therapies because they

have a better pharmaceutical effect remembering

that the use of artificial drugs is increasing greatly at

present(with potential for drug-resistant bacteria to

develop) (

Soleimani A et al, 2016).

The results from this study were also in

agreement with those found by Tursi et al ,2010. in

Italy, where 47.7% of UC patients that used

probiotics went into remission compared with only

32.4% of those who took a placebo, although

statistically not a very large increase, this was

possibly because the period of the study was too

short . A study by Sood et al, 2009. of 147 patients

in India found that taking probiotics had a

significant benefit whereby 41.9% went into

remission compared with only 15.7% from the

control group

. Tursi et al, 2010. used VSL#3 which

contains lactobacillus, bifidobacterium and

streptococcus thermophilus, with UC patients who

reported significant remission of their illnesses after

using it for 8 weeks.

The Impact of Probiotic Therapy on the Levels of Butyrate Acid in Inﬂammatory Bowel Disease

5 CONCLUSIONS

There was a significant increase in the levels of

butyrate acid in the faeces of IBD patients who got a

probiotik treatment compared to the control group of

IBD patients who only got a placebo but did not get

the probiotic treatment.

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