1
MD Neurology, China
2
Consultant Orthodontist, India
Corresponding author details:
Dr. Rajib Dutta
MD Neurology
India
Copyright:
© 2019 Roysarkar S, et al.
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Constipation is considered as a most predominant gastrointestinal non motor symptom
of Parkinson’s disease (PD) which occurs one or two decades before the diagnosis of PD.
The cause of constipation may be gut microbiota dysbiosis, neurodegeneration of enteric
nervous system causing dysmotility or sometimes no reason found. Irritable bowel
syndrome (IBS) on the other hand can cause constipation, diarrhoea or both. Researchers
think most common cause of IBS is related to stress. However recently, in addition to
constipation, a diagnosis of irritable bowel syndrome (IBS) was also found to be associated
with increased PD risk. Gut microbiota alterations is seen in both cases. It is also interesting
to note whether IBS like bowel symptoms comes with other non-motor symptoms together
or is a single identity. We are not sure whether IBS is a risk factor for developing PD in future
or IBS-C is just a non-motor symptom of PD. The pathophysiological connection between
these disorders are not known till date because of unavailability of studies.
Constipation, Non motor symptom, Parkinson’s disease, Irritable Bowel Syndrome,
Microbiota
IBS-C: Irritable bowel syndrome-constipation
IBS-D: Irritable bowel syndrome-diarrhea
IBS-M: Irritable bowel syndrome-mixed
IBS-U: Irritable bowel syndrome-unclassified
PIGD: postural instability and gait difficulty
TD: Tremor dominant
IND: Indeterminate
FC: Functional constipation
FGID: Functional Gastrointestinal Disorders
FBDSI: Functional Bowel Disorder Severity Index
IBS-SSI: Irritable bowel syndrome Symptom Severity Index
KP: Kynurenine pathway
NAE: N-acylethanolamine
SCFA: Short chain fatty acid
Parkinson’s disease is a neurodegenerative disease presents clinically with motor and non-motor symptoms [1]. The motor features mainly comprise of rigidity, bradykinesia, postural instability and resting tremor. The non-motor features include a variety of symptoms such as psychiatric abnormalities, executive dysfunction, autonomic dysfunction,sleep disturbance, sensory complaints, anosmia and gastrointestinal symptoms [2]. In clinical practice three motor phenotypes have been described in (PD): postural instability and gait difficulty (PIGD) dominant, tremor-dominant (TD), and indeterminate (IND) subtype [3]. Gastrointestinal symptoms are one of the most common non motor symptoms substantially hampering quality of life [4].
A lot of research has been done to understand the progression and pathophysiology of gastrointestinal dysfunction in Parkinson’s disease [5,6]. Important causes may include motor dysfunctions, autonomic dysfunctions, adverse effect of antiparkinsonian medications, microbiota dysbiosis,and enteric neurodegeneration to name a few [2,7,8]. Constipation can affect up to 70% of patients with PD [2]. It is also a frequent non motor symptom and is considered one of the strongest risk factors for PD [9,10]. Constipation is also emerging as one of the earliest features of autonomic dysfunction in Parkinson’s disease, developing as early as 15·3 years before motor features [11]. One study defined constipation as when patients had bowel movement less often than three times per week [12], whereas other researchers relied on a description from clinical records based on patients’ documentation [13]. A population-based study reported that risk of development of Parkinson’s disease increases with constipation severity (hazard ratios ranged from 3·3-4·2) [14]. The pathophysiological mechanisms behind constipation in PD include prolonged intestinal transit and pelvic floor dyssynergia [15,16]. Despite its high prevalence, no specific constipation questionnaire has been validated in PD patients [17].
The Rome III criteria is a standard method for assessing functional gastrointestinal disorders such as functional constipation (FC) and irritable bowel syndrome (IBS), since no biomarkers have been identified till date [18]. In the recently published updated Rome IV criteria, functional gastrointestinal disorders are defined as disorders of gut-brain axis interaction. Douglas A. Drossman has stated about Functional Gastrointestinal Disorders (FGID) as a group of disorders classified by gastrointestinal symptoms related to any combination of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, altered central nervous system processing [19]. Irritable bowel syndrome (IBS) on the other hand has subtypes like IBS constipation (IBS-C), IBS-diarrhoea (IBS-D), IBS-mixed (IBS-M), IBSunclassified (IBS-U) [20]. Drossman and colleagues also used FBDSI (Functional Bowel Disorder Severity Index), IBS-SSI (IBS Symptom Severity Index) to grade it into mild, moderate severe [21]. IBS is associated with an increased risk of developing PD in the Taiwanese population [22].
Dysregulation of the gut brain axis and alterations in the
composition of intestinal microbiota have been previously linked to
IBS pathogenesis and symptoms [23]. Several studies have reported a
higher relative abundance of Firmicutes and reduction in the relative
abundance of Bacteroidetes and Bifidobacteria in IBS patients [24,25].
The results for the abundance of Prevotella have not been consistent
[24,26]. Filip Scheperjans et al has reported previously persons with
a high abundance of Prevotellaceae was very unlikely to have PD
however low Prevotellaceae levels do not seem to be specific for PD,
because they have been reported in patients with autism and type
1 diabetes [27-29]. Changes in the gut microbiota might lead to low
grade inflammation and increased permeability of the gut mucosa
previously linked to IBS [30,31]. Gut mucosal changes have also been
reported in PD and it has been speculated whether this could initiate
alpha-synuclein associated neurodegeneration in the enteric nervous
system that subsequently spreads to the central nervous system as
initially proposed by Braak [32,33]. Study by T. H. Mertsalmi et al has
suggested Prevotellaceae emerged as a key species related to PD, and
now also to PD-associated IBS-like symptoms in their cohort [34].
In PD patients, IBS+ was associated with more reported nonmotor symptoms [34]. The prevalence of IBS in Japanese general population using ROME III criteria was (13.1–14.0%) [35], however Mishima et al has reported a prevalence of IBS in PD cohort was 17% [36]. Stool consistency and bowel affects can vary according to coffee intake, smoking, water intake, probiotics, insoluble fiber, beta blockers and other constipating agents taken over the counter. No study till date has considered these factors in a large group of study to draw a definite conclusion.
Rome IV criteria should be used to assess for more understanding of gastrointestinal dysfunction in PD. Procedures like colonoscopy has to be added to rule out any inflammatory, metabolic, anatomical or obstructive causes. A colon transit time can be useful test to rule out any another disease or explanation [37]. Gilles J Guillemin et al recently reported large kynurenine-to-tryptophan ratio due to the overexpression of kynurenine pathway (KP) enzymes is observed in different human health complications, including irritable bowel syndrome, inflammatory diseases, cancer, and neurodegenerative disorders. Gut microbiota can consume tryptophan and subsequently decrease its availability for the human body as this amino acid can be received from diet only [38]. Roberto Russo et al recently reported about lipids like N-acylethanolamine (NAE) and short chain fatty acids (SCFAs), such as butyrate can interact with gut-brain axis and can cause dysbiosis of microbiota which is involved in process of inflammation (IBS) and neurodegeneration like PD [39,40].
In summary we reviewed a common pathoclinical mechanism
of a subtype of IBS with constipation as a preclinical non motor
symptom of PD. Evidence definitely suggests a complex interaction
with gut-brain axis, inflammation and gastrointestinal microbiota
dysbiosis. Use of newest Rome IV questionnaire could provide a basis
for better understanding of the gastrointestinal dysfunction in PD.
We are not sure now whether IBS is a risk factor of PD because of lack
of studies till date. If the connection between IBS, PD, microbiota and
inflammation is confirmed by further studies, future research and
management in PD could profit from the accumulating evidence on
the pathophysiology and treatment of IBS.
The authors has no relevant affiliations or financial involvement
with any organization or entity with a financial interest in or
financial conflict with the subject matter or materials discussed in
the manuscript. This includes employment, consultancies, honoraria,
stock ownership or options, expert testimony, grants or patents
received or pending, or royalties. Special thanks to my supervisor
Professor Dr. Huifang Shang who gave initial ideas and supported me
through this research study.I would also like to thank Dr. Swatilekha
Roy Sarkar for her valuable feedback on the manuscript and literature
screening from PubMed.
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