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					perspective                                                                            0 E I SUE UC 1
                                                                                       N 9 WS P R O DN o : T 5




Using SCFA Percentage Distribution Patterns as
             Treatment Guides
Specific SCFA% Distribution Patterns Can Serve as an Additional Measure
             of the Composition of Predominant Bacteria

In our previous communication, we highlighted the fascinating phenomenon of ‘metabolic cross-feeding’ as
a means of explaining the diversity in patient response to prebiotics. This phenomenon essentially rests on
the fact that complex microbial communities such as that found in the human gastrointestinal tract involve
extensive metabolic interactions, where metabolic products produced from dietary prebiotics by one bacterial
species may provide substrates to support the growth of other populations. Cross-feeding between bacterial
species ultimately results in metabolic consequences that would not be predicted simply from the substrate
preferences of isolated groups of bacteria. These interactions can lead to changes in the composition of
predominant bacteria within the colon following the release of metabolic products such as short chain fatty
acids (SCFAs).
The distribution of SCFAs can provide an additional means of assessing the composition and diversity of
predominant bacteria. Abnormal SCFAs percentage distribution patterns such as that shown below for a 65
year old male; are an indication the patient may not possess certain species of bacteria which would normally
metabolize non-digestable polysaccharides and oligosaccharides down to the major SCFAs such as butyrate,
propionate, and valerate, which happen to be low in this patient.
The patient referred to above presented to his doctor complaining mainly of significant bloating after eating a
wide range of foods. Onset of bloating followed a trip to India 5 years ago. Other than this, the patient carries
some excess abdominal fat, which is likely to be partly associated with his affection for regular alcohol intake.
The doctor noted that the patient is reluctant to change this aspect of his lifestyle. The patient however, does
exercise regularly, jogging most days, as a means to manage his weight and alcohol intake.




Perspective - 09 ISSUE No:15       In Focus: Using SCFA Percentage Distribution Patterns as Treatment Guides
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The Gastrointestinal Function Profile for this patient was also positive for the parasite DNA probe,
Strongyloides sp. The doctor treated this with Ivermectin and follow-up testing showed eradication of the
parasite, however, the patient noted only a temporary marginal improvement in his bloating.

SCFAs as a Measure of Intestinal Dysbiosis
It is interesting to note that if we consider the predominant bacteria panel alone as a measure of intestinal
dysbiosis, we might conclude that the patient has negligible dysbiosis. However, the severity of abnormalities
in the percentage distribution of SCFAs suggests this patient has significant intestinal dysbiosis. A recent
statistical analysis of 775 consecutive samples for Gastrointestinal Function Profiles revealed only 5 reports
displaying abnormal values for all the SCFAs percentage parameters. This reinforces the severity of the
abnormal distribution of SCFAs for this patient. Despite the relatively normal levels of predominant bacteria in
this patients’ stool specimen, we can reasonably assume that the composition of the predominant bacteria is
significantly perturbed due to the highly abnormal SCFAs percentage distribution.

Multi-Strain Probiotics Important when SCFAs Abnormal
A high-potency, multi-strain probiotic, such as VSL#3 may have been warranted for this patient. Such a product
would provide a number of bacterial strains which, via cross-feeding mechanisms may be able to raise the
levels of SCFAs butyrate, propionate and valerate and decrease the percentage level of acetate. A study on
the use of VSL#3 in patients with irritable bowel syndrome (IBS) with bloating showed a significant reduction in
flatulence after supplementation with 2 satchets per day (i.e. 900 billion cfu’s) over 4 weeks.1 When attempting
to explain the possible mechanisms behind the positive findings, the authors state that VSL#3 may alter the
resident colonic microflora leading to a modification in the colonic metabolism of nutrient substrates with a
resultant change in the production of SCFAs. SCFAs can induce propulsive contractions and accelerate colonic
transit,2 or ehance fluid and sodium absorption in the colon,3 thus providing an mechanistic explanation for the
positive effects of VSL#3 on symptoms of flatulence in this study.

Dosing of Probiotics May Be Key to Treatment Success
Recent studies using high dosages of VSL#3 have reported positive outcomes with regard to the induction and
maintenance of remission in both adult and child patients with ulcerative collitis.4-8 The most recent study gave
77 patients with mild-to-moderate ulcerative collitis (UC) 8 sathcets of VSL#3 twice daily for 12 weeks. 33 of
the patients or 42.9% acheived remission at the end of the 12 week study period. This was significantly higher
than the 11 patients in the control group who only reveived a placebo.4
These are quite astounding results for a probiotic-only intervention in a well-known inflammatory bowel
condition such as UC. It is important to note however, the dosage and length of treatment used in this study
(i.e. 16 satchets a day or 7.2 trillion cfu’s per day for 12 weeks). This dose is certainly much higher than the
average probiotic dose prescribed by clinicians specialising in nutritional medicine.
Of the other studies reporting positive effects of VSL#3 on conditions such as inflammatory bowel disease,5-8
irritable bowel syndrome,1 pouchitis,9-11 liver disease,12 radiation-induced diarrhea in cancer patients,13
diverticulitis,14, 15 ileal pouch anal anastomosis16 and rotavirus diarrhea in children;17 doses ranging from 1 to 8
satchets have been used. This still equates to between 450 billion cfu’s and 3.6 trilion cfu’s per day, which is
much higher than the typical dose of probiotics prescribed nowadays. It leads one to question the effectiveness
of the common dosing regime for probiotics. Daily doses of probiotics such as those used in the above studies
may be what is required to acheive significant therapeutic effects in inflammatory bowel conditions such as
ulcerative collitis and Crohn’s disease.


References
1. Kim HJ, et al. A randomized controlled trial of a probiotic combination VSL#3 and placebo in irritable bowel syndrome with
bloating. Neurogastroenterology and Motility. 2005;17(5):687-96.
2. Kamath PS, et al. Colonic capacitance and transit in man: modulation by luminal contents and drugs. Gut. 1990;31(4):443-
449.
3. Binder HJ & Mehta P. Short-chain fatty acids stimulate active sodium and chloride absorption in vitro in the rat distal
colon. Gastroenterology. 1989;96(4):989-996.
4. Sood A, et al. The probiotic preparation, VSL#3, induces remission in patients with mild-to-moderately active ulcerative
colitis. Clinical Gastroenterology and Hepatology. 2009 Jul 22. [Epub ahead of print]
5. Miele E, et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with
ulcerative colitis. American Journal of Gastroenterology. 2009;104(2):437-443.
6. Huynh HQ, et al. Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis:
a pilot study. Inflammatory Bowel Disease. 2009;15(5):760-768.
7. Bibiloni R, et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. American Journal of

Perspective - 09 ISSUE No: 15          In Focus: Using SCFA Percentage Distribution Patterns as Treatment Guides
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Gastroenterology. 2005;100(7):1539-1546.
8. Tursi A, et al. Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or
mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. Medical Science Monitor. 2004;10(11):PI126-PI131.
9. Kuhbacher T, et al. Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut.
2006;55(6):833-841.
10. Mimura T, et al. Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory
pouchitis. Gut. 2004;53(1):108-114.
11. Gionchetti P, et al. High-dose probiotics for the treatment of active pouchitis. Diseases of the Colon and Rectum.
2007;50(12):2075-2082.
12. Loguercio C, et al. Beneficial effects of a probiotic VSL#3 on parameters of liver dysfunction in chronic liver diseases.
Journal of Clinical Gastroenterology. 2005;39(6):540-543.
13. Delia P, et al. Use of probiotics for prevention of radiation-induced diarrhea. World Journal of Gastroenterology.
2007;13(6):912-915.
14. Tursi A, et al. Beclomethasone dipropionate plus VSL#3 for the treatment of mild to moderate diverticular colotis: an
open, pilot study. Journal of Clinical Gastroenterology. 2005;39(7):644-645.
15. Tursi A, et al. Basalazide and/or high-potency probiotic mixture (VSL#3) in maintaining remission after attack of acute,
uncomplicated diverticulitis of the colon. International Journal of Colorectal Disease. 2007;22(9):1103-1108.
16. Pronio A, et al. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated
with expansion of mucosal regulatory cells. Inflammatory Bowel Disease. 2008;14(5):662-668.
17. Dubey AP, et al. Use of VSL#3 in the treatment of rotavirus diarrhea in children: preliminary results. Journal of Clinical
Gastroenterology. 2008;42(Suppl 3 Pt 1):S126-S129.




Perspective - 09 ISSUE No: 15           In Focus: Using SCFA Percentage Distribution Patterns as Treatment Guides

				
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