Ozone Therapy and Gut Microbiota in Constipation-Predominant IBS: A 2018 Randomised Study

Background: gut bacteria in constipation-predominant IBS

Changes in the intestinal microbiota are considered one of the central mechanisms in irritable bowel syndrome, with shifts in the qualitative and quantitative make-up of gut organisms contributing to chronic intestinal inflammation.

Conventional management of intestinal dysbiosis draws on a wide pharmacological arsenal - antispasmodics, intestinal antiseptics, eubiotics, pre- and probiotics, synbiotics and vitamins. The author's stated starting point is that no effective scheme for correcting dysbiotic disturbance in IBS has yet been established, and that drug therapy does not always produce the desired effect, which is what prompted the search for other approaches.

Study design: 48 patients, randomised into two groups

The study was carried out by R.M. Mallayeva at Dagestan State Medical University in Makhachkala, Russia, and published in 2018 in Modern Issues of Biomedicine.

Forty-eight patients with a verified diagnosis of IBS with constipation took part. All were aged between 18 and 40, with disease duration of three to ten years, and all gave written informed consent. Simple randomisation assigned them to two groups.

Control group (20 patients): drug treatment with dicetel, plus interference therapy delivered by an INTERDIN ID79M device using an orbital-occipital method at 90-100 Hz, current no greater than 30 mA, 20 minutes daily for ten sessions.

Main group (28 patients): the same drug and interference therapy, with ozone added. This consisted of ozonated distilled water at a dissolved ozone concentration of 5 mg/l, taken 150 ml three times daily 30 minutes before meals for three weeks, together with eight rectal insufflations of an ozone-oxygen mixture at 15 mg/l in a volume of 200 ml. Both were produced using a Medozon UOTA 60-01 device.

It is worth being clear that this was a supervised clinical protocol delivered alongside prescription medication in a medical setting. It is a description of what was studied, not a set of instructions.

What was measured

At the start and end of the treatment course, all patients had the qualitative and quantitative composition of their large intestine microflora determined by culture, radiological examination of the intestine tracking the passage of barium through the colon, and quality of life assessed using the Russian-language version of the MOS SF-36 questionnaire across both physical and psychosocial profiles. Differences were treated as statistically significant at p < 0.05.

Findings: intestinal microflora

The ozone group showed better results than the control group across both beneficial and harmful organisms.

Bifidobacteria and lactobacilli increased in 73.7% of ozone-group patients by the end of treatment. In the control group, bifidobacteria increased in 47.1% of cases and lactobacilli in 47.4% (p < 0.05 between groups). Normal E. coli counts increased in 85.7% of the ozone group against 60% of controls.

Among less desirable organisms, E. coli with altered enzymatic properties returned to normal in 66.7% of the ozone group against 33.3% of controls (p < 0.05 between groups). Enterococci improved in 72.7% of the ozone group against 53.8% of controls. Staphylococcus aureus fell in 66.7% of the ozone group against 42.8% of controls. Haemolysing E. coli fell in 84.6% of the ozone group against 50% of controls. Candida cleared in five of six ozone-group patients who had it, with a reduction reported in 60% of control-group cases.

The author attributes the improvement to the anti-inflammatory, bactericidal and antifungal effects of ozone.

Findings: bowel transit and quality of life

On radiological examination, positive change was seen in an average of 89.5% of the ozone group against 60.5% of controls. Looking at the two patterns separately, hypomotor dyskinesia with colonic hypertonus improved by 88.2% in the ozone group against 63.6% in controls, and hypomotor dyskinesia with hypotonus by 90.9% against 57.2%.

Correlation analysis found a clear relationship between normalised defecation frequency and barium transit time (r = +0.74, p < 0.001), and between normalised defecation frequency and improved microbiota (r = +0.64, p < 0.001). The author reads this as indirect evidence of a prokinetic effect.

On the SF-36, the ozone group scored higher than controls for both psychological health (64.8 plus or minus 3.24 against 53.1 plus or minus 3.19, p < 0.05) and physical health (67.7 plus or minus 4.52 against 56.1 plus or minus 4.48, p < 0.05). Both groups remained below the reference norms of 72.6 and 75.4 respectively.

A note on the published abstract

Both the Russian and English abstracts state that ozone therapy produced an increase in pathogenic microbiota - yeast-like fungi, Staphylococcus aureus and E. coli with altered enzymatic properties. The body of the paper reports the opposite for all three, and the conclusion drawn from those results is that the treatment corrected dysbiotic shifts. This appears to be a typographical error in the abstract, repeated in the concluding paragraph. We have reported the results as given in the body of the paper.

Limitations

This is a small single-centre study of 48 patients, published in a regional Russian journal by a single author, and it does not appear in PubMed, Scopus or DOAJ. There has been no independent replication.

There was no blinding and no placebo. The control group received an active treatment, and the ozone group received everything the control group received plus two additional interventions - ozonated water taken orally and rectal insufflation - so the study cannot attribute the difference to either one, nor separate the effect of ozone from the effect of additional treatment contact. Despite simple randomisation the groups were unequal in size, at 20 and 28.

Most of the microbiota results are reported as the percentage of patients who improved rather than as measured bacterial counts, and several of the between-group comparisons are presented without a p value attached. The Candida finding rests on six patients. No correction for multiple comparisons is described. Outcomes were assessed at the end of a three-week course with no longer-term follow-up, so nothing can be said about whether the changes persisted.

The study population was specifically IBS with constipation, in adults aged 18 to 40 with established disease. The findings should not be generalised to other IBS subtypes or to other gastrointestinal conditions.

Irritable bowel syndrome should be diagnosed by a doctor, as symptoms resembling IBS can have other causes. Anyone considering ozone therapy alongside treatment for a gastrointestinal condition should discuss it with their own clinician.

Mallayeva RM. The Influence of Ozone Therapy on the Condition of Intestinal Microbiota. Modern Issues of Biomedicine. 2018;2(1):108-114. Published in Russian with an English abstract; the journal archive is accessible only from Russia, Belarus, Kazakhstan and Uzbekistan.