Changes in the composition of gut microflora (bacteria) have been associated with an increase in chronic diseases, such as obesity, type 2 diabetes mellitus, metabolic syndrome and atherosclerosis. Interestingly, these associations have led researchers to suggest that changes in the composition of the microflora of the gut may also occur in other chronic diseases such as Parkinson’s disease (PD). This is a notable concept worth exploration, in the context of early stage PD dysautonomic gastrointestinal symptoms, characterised by dysphagia, slow gastric emptying and constipation. Moreover, very recent investigations have suggested that changes in the gut microbiota and increased gut permeability, inflammation, neuro-inflammation and small intestinal bacterial overgrowth (SIBO) could contribute to the pathogenesis of PD.
Growth of gut microbiota is associated with the release of bacterial metabolism products, which are absorbed by the intestine, enter human metabolism and are eliminated in the urine. One of these compounds is indoxyl sulfate, otherwise known as indican. The urinary concentration of indican can be measured by a simple and inexpensive procedure, which has been employed to assess dysbiosis and SIBO. In healthy subjects indican urinary concentrations are low (approximately 10-25 mg/l), since bacterial growth in the upper intestine is very modest. High concentrations (> 40 mg/l) indicate changes in bacterial growth in the small intestine, such as SIBO, malabsorption and constipation. In the presence of SIBO or malabsorption, the intraluminal concentration of amino acids increases and, in turn, so does bacterial conversion of tryptophan to indican. In constipated subjects the increase in indican concentrations is likely the result of changes in gut flora – such as reduction in lactobacillus strains.
In a recent study (2015) undertaken by the Parkinson’s Institute of Milan in association with the Faculty of Medicine and Surgery at the University of Milan, Italy, researchers sought to measure indican urinary concentrations, as surrogate of changes in the gut microflora in three groups of subjects: PD patients at onset of disease; PD patients on levodopa treatment and age and gender-matched healthy controls. In patients diagnosed with PD, indican urinary concentrations were approximately two times higher compared to healthy subjects (46.4 +/- 4.1 mg/l vs 24.9 +/- 4.6 mg/l). Results highlighted that the difference in concentration did not appear to be influenced by differences in:
- Body Mass Index (BMI)
- Dietary Habits
- Intestinal Function – Given that concentrations were not affected by the presence of constipation.
Interestingly, urinary indole concentrations were significantly higher in de novo PD patients (onset of Parkinson, not using levodopa), suggesting that disease duration and pharmacological therapy of PD do not play a role. The authors note that the validity of their findings is supported by:
- The consistency of their data, with the results of the few studies published in the literature, which report that the mean indican urinary concentration in healthy men is approximately 10-25 mg/l.
- That despite the recruitment of PD patients at a specialised tertiary care setting perhaps resulting in potential inclusion bias, the sample was likely representative of the general PD population since the prevalence of constipation (60%) was consistent with the data in the literature.
What is fascinating is that the researchers suggest the occurrence of dysbiosis prior to the onset of PD; independent of the presence of constipation, and that it is not affected by disease duration and/or pharmacological treatment. For this reason, the researchers hypothesize that high urinary indican concentrations could even have a role in the pathogenesis (origin) of PD. This is not as far-fetched as it seems, when we consider that researchers have observed impaired tryptophan metabolism in PD patients, with a significant reduction in tryptophan metabolites in both plasma and cerebrospinal fluid. Moreover, that normalisation of tryptophan metabolism may result in neuro-protection. This being so, that increased bacterial conversion of tryptophan to indican is indicated in SIBO and dysbiosis there are perhaps links between gut microbiota and neuro-protection in PD.
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