By David Kiefer, MD, Editor
Clinical Assistant Professor, Department of Family Medicine, University of Wisconsin; Clinical Assistant Professor of Medicine, Arizona Center for Integrative Medicine, University of Arizona, Tucson
Dr. Kiefer reports no financial relationships relevant to this field of study.
- The authors enrolled 53 people with irritable bowel syndrome (IBS) refractory to other IBS treatments; 45 participants completed 12 weekly sessions of gut-directed hypnotherapy.
- Data were analyzed for 38 people. There were no significant changes in the microbiome, but there were improvements in IBS symptoms.
Gut-directed hypnotherapy provided improvement in irritable bowel syndrome symptoms but failed to cause significant changes in study participants’ microbiome.
Peter J, Fournier C, Keip B, et al. Intestinal microbiome in irritable bowel syndrome before and after gut-directed hypnotherapy. Int J Mol Sci 2018; Nov 16;19(11). pii: E3619. doi: 10.3390/ijms19113619.
Mind-body research involves many disciplines and has shown promising results regarding physiological effects and improvements in several clinical conditions. Fascinating explorations into the “brain-gut” connection, the proverbial “gut feeling,” have elicited profound connections, many of them mediated by the vagus nerve. More recently, this vagus highway has been shown to be bidirectional and may be related to the status of the microbiome. Into this milieu stepped Peter et al, as they investigated changes in the microbiome in people with irritable bowel syndrome (IBS) who underwent gut-directed hypnotherapy (GDH).
To further understand the rationale for using this disease state and intervention, it is helpful to look beyond the psychological connection with IBS symptoms, a common and known phenomenon, to results coming out of the same research group showing that there are associations between psyche and microbiome.1 Considering these factors, would it be possible to adjust the microbiome in patients with IBS through a mind-body technique such as GDH?
The study took place in Austria, and the researchers recruited people with IBS, diagnosed by the Rome III criteria, who had failed other treatments. They excluded people who were pregnant or developmentally delayed, or who had prior bowel surgery, “severe organic disease,” schizophrenia/psychosis, substance use disorder, panic attacks, lack of fluency in German, or had taken antibiotics within the last month. Of the 63 people screened, 53 were enrolled, 48 were analyzed statistically, but only 45 completed the GDH. The authors analyzed data from only 38 study participants; no description was included to account for the dropouts
The GDH involved ten 45-minute sessions, weekly over a 12 week period, in a group of five to seven people. It was administered by two members of the research team. A CD recording was made of the first session, and participants were asked to listen to the recording once daily between classes.
Stool samples were collected by participants two times, before the intervention and after completion of the GDH classes, then brought frozen to the study laboratory for analysis. A variety of surveys also were given to study participants, both before and after the intervention. One example is the IBS Severity Scoring System (IBSSSS), ranging from 0 to 500, including mild (75 to 175), moderate (175 to 300), and severe (300 to 500) symptoms. Participants were asked about general, physical, and psychological well-being, each ranging from 0 to 100, for a total score of 0 to 300, as well as anxiety and depression (14 questions, 0 to 3 each), another series of IBS symptom questions (0-100), and a yes/no question about the success of treatment. Finally, a seven-day food diary (food frequency questionnaire) was collected for each of the study participants.
As mentioned above, data were collected from 38 study participants, who had a mean age of 44 years and mostly suffered from diarrhea-predominant or mixed-type IBS. With respect to the microbiome, no statistically significant differences were seen pre- and post-intervention, although some trends in bacterial changes were documented. (See Table 1.) The researchers interpreted these changes as showing a slight increase of gram-positive bacteria and less gram-negative bacteria. In addition, using correlative statistical techniques, relationships between symptomatic changes and microbiome shifts were analyzed, but, again, no significant correlations were seen among 17 trends. The strongest of these trends involved Oscillibacter species. With respect to symptoms, more convincing improvements in a variety of parameters were seen. (See Table 2.)
Table 1: Changes in Bacterial Concentrations Pre- and Post-GDH Intervention
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- Reduction in bacteria in the family Lachnospiraceae
- Firmicutes:Bacteroidetes ratio decreased
Note: These differences were not statistically significant.
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Table 2: Changes in IBS Symptoms After Completion of Gut-Directed Hypnotherapy
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- IBSSSS: decreased from 323 to 264 (q < 0.01)
- Well being: increased from 105 to 151 (P < 0.01)
- Psychological stress: decreased from 17 to 12 (P < 0.01)
- No change in constipation (P = 0.19); diarrhea, bloating, pain all decreased (P < 0.001)
- Adequate relief: 84% of study participants (P value not provided)
Statistical significance in parentheses
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COMMENTARY
As the authors mentioned, this was a ground-breaking attempt to find a bacterial explanation for the recent explosion in brain-gut research. As it turns out, GDH did not lead to significant changes in the microbiome; nonetheless, some lessons can be learned from the results. For example, more than anything, this study was a commentary on a possible mechanism of action of GDH, which the authors noted has efficacy in IBS, although “… relatively little is known about its pathways of action.” From the results of this study, we can say that GDH may, as the researchers posit, act on the central nervous system, not the gut, or somatic processing mechanisms. One of the important mind-body techniques, GDH may be more mind than body, if the results of this study are believed.
With respect to study limitations, the authors correctly pointed out the small sample size and lack of a control group as compromising the study results. It would be very interesting to see whether the bacterial trends continued, statistically so, in a more robust clinical trial. As the authors noted, some prior research correlates a lower Firmicutes:Bacteroidetes ratio with more “healthy” gastrointestinal function and overall health. In addition, alterations in these two bacteria genera, some of the most common in the human colon, have been seen in obesity and metabolic syndrome.2,3 The nonsignificant changes in Oscillibacter are interesting, as the researchers mentioned past studies showing a direct relationship of levels of this bacterium with depression. A corroboration of these trends would be an important next step.
Despite the lack of a strong microbial association with this study’s GDH intervention, clinicians still should take note of the symptomatic efficacy seen in this cohort of IBS patients who had tried and failed other IBS treatments. The demographic here, mostly mixed or diarrhea-predominant IBS, might guide our clinical suggestions of who would benefit from GDH, although there is no reason to think that constipation-predominant IBS would not respond to this therapy. This study also had many exclusions, another factor to keep in mind should clinicians decide to apply these results to specific patients in their practice. Obviously, a repeat study with a control group is needed to see if those symptomatic improvements are real and are not an artifact of the placebo effect.
A full evaluation of any therapy would explore possible adverse effects or contraindications. Peter et al did not document this type of information, although experts list only a few cautions for the use of this technique, such as how it may not be appropriate in individuals with severe mental illness.4 Considering these results, GDH may have a role for people with IBS, especially when aiming to help with symptom control, even in the absence of significant gastrointestinal microbial changes.
REFERENCES
- Peter J, Fournier C, Durdevic M, et al. A microbial signature of psychological distress in irritable bowel syndrome. Psychosom Med 2018;80:698-709.
- Festi D, Schiumerini R, Eusebi LH, et al. Gut microbiota and metabolic syndrome. World J Gastroenterol 2014;20:16079-16094.
- De Vadder F, Kovatcheva-Datchary P, Goncalves D, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell 2014;16:156:84-96
- Mayo Clinic. Hypnosis. Available at: https://mayocl.in/2IZ1LrY. Accessed: March 12, 2019.
