Gut Microbiome Changes with Osteopathic Treatment of Constipation in Parkinson’s Disease, a Pilot Study

Participants

• Number: 6 people (3 female and 3 male, mean age 72 years)

• Criteria of inclusion: age ≥ 40 years, medical diagnosis of Parkinson’s disease, diagnosis of constipation according to the Rome III criteria and ability to provide stool pictures for examination

• Criteria of exclusion: age < < < 40 years; no diagnosis of Parkinson’s disease; presence of other neurological diseases or constipation related disorders (with the exception of headache and migraine); cancers of the colon, pelvis, gastrointestinal tract or abdomen; unexplainable or new onset of signs of fever, night sweats and weight loss; rectal bleeding and black stool; not medically evaluated anemia; acute hepatitis; acute mononucleosis; splenomegaly, irritable colon syndrome; aortic abdominal aneurysm; other known or unknown secondary causes for chronic constipation (eg, organic pathologies or congenital malformations); pregnancy, inability to tolerate OMT or presence of contraindications; unable to provide stool photos for the examination; acute gastrointestinal infection or oral antibiotic consumption over the past month; abdominal or pelvic surgery over the past 6 weeks.

• Groups of study: 1 group
  • Group 1: 6 people
  originally 9 people but 3 had to drop out during the first weeks due to urinary tract infection, problems in collecting stool samples and inability to comply with the visit schedule

The interventions were applied according to the following modality:

• 4 weeks: no treatment
• 4 weeks: OMT
• 2 weeks: no treatment

Interventions and evaluations

• Study carried out over 10 weekly visits
• To assess the inclusion or exclusion criteria for the study:
  • evaluation of severity of Parkinson’s disease through the Movement Disorder Society (MDS) Unified PD Rating Scale (UPDRS)
  • collection of data related to medical history, new therapies, tobacco use, medication and supplement consumption over the past month, gastrointestinal symptoms, fluid and coffee intake, physical activity, number of bowel movements, fermented food, prebiotics or probiotics consumption
• Weekly evaluation of changes in medical history, in onset of new diseases and in perceived treatment effectiveness
• Weekly evaluation of constipation severity through Wexner Cleveland Constipation Scoring System (WCCSS), constipation symptoms through Patient Assessment of Constipation-Symptom (PAC-SYM) and quality of life through Patient Assessment of Constipation-Quality of Life (PAC-QOL)
• Evaluation of gut microbiota on stool samples at visits 3, 5, 7, 9 and at the end of the study

• calcolo dello Shannon Diversity Index (SDI) per la diversità generale

• calculation of the correlations between microbiome composition and other measured outcomes before applying OMT

• Weekly evaluation of stool consistency through Bristol Stool Chart

• the physicians examined the photos provided by the participants

• 4 weekly sessions of OMT between weeks 5 and 8
• OMT: standardized according to a sequence of techniques, each applied for 2 minutes

• techniques directed to the autonomic nervous system: suboccipital release, celiac, superior mesenteric and inferior mesenteric ganglion inhibition, bilateral paraspinal inhibition of the segments T10-L2, bilateral sacroiliac joint decompression, sacral rocking
• techniques directed to the enteric nervous system: mesenteric release of ascending and descending colon, colonic stimulation

• techniques directed to the diaphragm: respiratory diaphragm release
• techniques directed to the pelvis: bilateral sacroiliac joint decompression

• OMT applied by an osteopathic physician
• The participants were instructed not to change, and indeed to document, their use of medications or supplements and their eating habits

Results

• Outcome primari: OMT led to a statistically significant improvement in severity of constipation measured on WCCSS, in constipation symptoms measured on PAC-SYM and in quality of life assessed via PAC-QOL. All these improvements showed a high effect size (actual relevance of the intervention).The stool consistency measured on Bristol Stool Chart also improved, but not in a statistically significant manner.
  As for the state of the microbiota, there were no effects on the SDI, that is, on the general diversity of the microbiota. However, the number of families of the phylum Firmicutes decreased statistically significantly, although the number of microbes of this phylum increased (the Ruminococcaceae increased significantly).

With regard to other phylia, a statistically significant increase in Proteobacteria and Fibrobacteres occurred, whereas Actinobacteria, Verrucomicrobia, Bacteroidetes and Euryarchaeota decreased. All these results showed a medium-high effect size.
Similarly, the abundance in genus Intestimonas decreased while the abundance of genus Roseburia increased after OMT.
With regard to the correlations between microbes and measured outcomes, in a statistically significant manner, Actinobacteria as a phylum and Roseburia as a genus were negatively correlated to the severity of Parkinson’s disease (ie, a higher number of these microbes were linked to better health) and positively with quality of life, while Euryarchaeota, Fibrobacteres, Synergistetes, and Verrucomicrobia as phyla, and Intestimonias as a genus were shown to be positively correlated with the severity of Parkinson’s disease. Finally, Bacteroidetes were found to be negatively related to quality of life. Finally, Bacteroidetes were found to be negatively related to quality of life.

• Further analysis: the possible confounding factors did not change during the visits.

No adverse effects were detected.

Discussion

In line with past studies, OMT improved the severity and symptomatology of constipation and the quality of life related to it. Interestingly, OMT also seems to have had an impact on the composition of the microbiota, also involving those microbes related to the severity of Parkinson’s disease.
For example, the Roseburia, low at the beginning of the study and positively correlated to good health, increased after OMT, while, vice versa, the Intestimonas, high at the beginning of the study and negatively related to health, decreased after OMT.

There were also other effects worthy of an in depth analysis in future larger and more robust studies as they involved microbes (eg, Verrucomicrobia, Firmicutes, Bacteroidetes, Prevotella) that in recent years have been used to identify people with Parkinson’s disease and discriminate their severity.

Like any pilot study, this study presents the limitations of its organization, first of all the data collection, which requires more advanced tools, in real time and easier to use.