The Brain, the Gut, the Food, and the Bacteria? Update on Treatment of Functional Gastrointestinal Disorders
Probiotics vs Antibiotics
[A snip from Medscape.
medscape.com ]
In a small (n = 44) study, Faber[8] examined the effect of probiotics* alone (n = 20) and in combination with antibiotics (n = 24) on GI symptoms and QOL in an uncontrolled trial of unselected (all subtypes) patients with IBS. Antibiotic treatment included ciprofloxacin* 500 mg twice daily per week, and probiotic treatment included Lactobacillus acidophilus NCFM (10 billion/g) and Bifidobacteria infantis (10 billion/g) daily for 4 weeks. Both groups showed significant improvement following treatment: In the probiotic/antibiotic group, a decrease in symptom frequency index scores from 35 to 18 (P < .001) and an increase in IBS-QOL scores from 67.6 to 87.8 (P < .001) were seen; in the probiotic-only group, a decrease in symptom frequency index scores from 39 to 17 (P < .001) and an increase in IBS-QOL scores from 69.3 to 86.4 (P < .001) were seen. The predominant IBS type did not alter the response to therapy.
Commentary. As a small uncontrolled study, these results may reflect, at least in part, a placebo response. Nevertheless, the findings emphasize the need for additional clinical studies to evaluate the role of probiotics and antibiotics in IBS patients.
Mechanisms of Probiotics
Although the efficacy and role of probiotics in the treatment of IBS remain uncertain and require confirmation, several studies presented during this year's meeting examined possible mechanisms for their effects on GI motor, sensory, and immune function.
Lamine and colleagues[9] investigated the effect of treatment with Lactobacillus farciminis bacteria on the nociceptive response to colorectal distension in basal conditions and after TNBS (2,4,6-trinitrobenzene sulfonic acid)-induced colonic inflammation in rats. They found that L farciminis treatment significantly reduced (P < .05) abdominal nociceptive response for all distending pressures in both the noninflamed-treated group compared with the noninflamed controls and in the TNBS-induced inflamed hypersensitivity treated group compared with the nontreated group. These researchers attributed this antinociceptive effect to the known ability of L farciminis to produce nitric oxide (NO). Indeed, hemoglobin (an NO scavenger) infusion resulted in reversing this organism's antinociceptive effect. These investigators concluded that a 3-week treatment with L farciminis can reduce visceral pain induced by colorectal distension in basal and inflammatory conditions, and that this effect depends on the NO released by these bacterial strains into the colonic lumen.
In another study, the same group of investigators reported a protective effect of the NO producing-L farciminis against TNBS-induced colitis in rats.[10] Rats that were treated with this organism for 3 weeks prior to induction of colitis showed significantly lower inflammation, as expressed by reduction in macroscopic damage score, MPO (myeloperoxidase) activity, and inducible NO synthase activities. As with the previous study, hemoglobin reversed the beneficial effect of L farciminis on the inflammation activity in the colitic rats.
Commentary. These studies suggest a role for NO-producing bacteria in protecting against inflammatory and hypersensitivity conditions. However, these findings in animal models deserve additional investigation in humans in order to confirm beneficial effects.
Another possible mechanism mediating the effects of probiotic bacteria on GI function has been proposed by Verdu and colleagues.[11] They investigated the effects of probiotics on intestinal muscle dysfunction in a mouse model of postinfective Trichinella spiralis IBS. Study mice groups were treated with Lactobacillus paracasei, Lactobacillus johnsonii, Bifidobacterium longum, or B lactis. Additional mice received heat-inactivated L paracasei or bacteria-free L paracasei spent culture medium (SCM). At 21 days post infection, L paracasei, but not L johnsonii, showed significant attenuation of hypercontractility to carbachol stimulation, compared with the control group (P = .01). The 2 bifidobacteria strains tended to decrease the hypercontractility; however, this trend did not reach statistical significance (P = .09). The attenuation of muscle hypercontractility was paralleled by a 2-fold decrease in the secretion of interleukin-4 (P < .0001), mRNA for transforming growth factor-beta (P = .0001), and cyclooxygenase-2 (P = .001) in longitudinal myenteric plexus preparation and by modulation of genes involved in innate defenses such as RANTES and cryptdin, as evaluated by gene array analysis.
Commentary. It is interesting that the normalization of the postinfection contractility was independent of L paracasei presence in the mucosa-associated flora -- thus indicating that the improvement in intestinal muscle dysfunction by L paracasei and free-L paracasei SCM is likely due to attenuation of cytokine and inflammatory mediator production in the muscularis externa and modulation of innate defense genes in the small intestine. In addition, this effect is strain-dependent.
The importance of the strain-specific effect has also been suggested by findings from other studies.[12] The clinical implication for this strain-specific effect has been shown in an interesting abstract presented by Drisko and colleagues.[13] These investigators examined 5 commercially, commonly available probiotic products. They used polymerase chain reaction (PCR) gel electrophoresis and amplicon excision with DNA sequencing to determine the bacterial strain content of these 5 products and compared their findings against what was reported in the respective product labeling information.
These investigators found that with a single exception, all bacterial species that were tested were detected in the probiotic samples by PCR analysis and confirmed by DNA sequencing. Bifidobacterium bifidum was not detected in 2 of the 5 samples reporting its presence. In contrast, Lactobacillus spp. were detected in 2 of the 5 product samples for which the species was not listed as an "ingredient."
Commentary. Although cultures of commercially available probiotics closely resemble their labeling information overall, there are some differences. Because emerging data suggest that the beneficial effect of probiotics is strain-dependent, a better regulation of dietary supplements may be necessary to ensure proper preparation and marketing standards.
Concluding Remarks
The above discussion is intended to bring to the fore the current state of knowledge regarding the multifactorial nature of FGIDs. Within this context, new insight may be gained with respect to the clinical and therapeutic implications for patients with these disorders, with a view toward the effect and effectiveness of available and commonly used treatment options.
* The United States Food and Drug Administration has not approved this medication for this use. |
