Small intestine dysfunction in Parkinson’s disease

Dutkiewicz, Justyna; Szlufik, Stanisław; Nieciecki, Michał; Charzyńska, Ingeborga; Królicki, Leszek; Smektała, Piotr; Friedman, Andrzej

doi:10.1007/s00702-015-1442-0

Cited by 39 publications

(23 citation statements)

References 13 publications

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Section: Constipationmentioning

confidence: 99%

“…78,79 Constipation occurs mainly due to delayed intestinal transit time and its effects are displayed in the small intestine and colon. 78,79 It is believed that constipation appears as a prodromal symptom years before the motor symptoms appear. 80 It has been reported that men, in their middle age, with less than one bowel movement per day had 4 times the risk of PD diagnosis for the next 20-25 years compared to men who had normal bowel movements.…”

Section: Constipationmentioning

confidence: 99%

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Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Nair

Ramachandran

Joghee

et al. 2018

J Neurogastroenterol Motil

118

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Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients.

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Section: Constipationmentioning

confidence: 99%

Section: Constipationmentioning

confidence: 99%

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Nair

Ramachandran

Joghee

et al. 2018

J Neurogastroenterol Motil

118

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“…Intestinal symptoms observed in PD are consistent with conditions of inflammation. Constipation in PD patients is attributed to slow intestinal transit time, a symptom that is also frequently observed in other conditions involving chronic GI inflammation such as inflammatory bowel disease (IBD) and obesity . Mechanistically, this condition has been linked to intestinal immune activation and to intestinal dysbiosis, which is another hallmark of disorders involving gut inflammation .…”

mentioning

confidence: 99%

Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's Disease

et al. 2018

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“…Studies on asymptomatic ileostomy subjects established that the core ileal microbiota consists of (facultative) anaerobes including species from Clostridium Cluster I (Booijink et al, 2010;Zoetendal et al, 2012). Moreover, the transit time in the SI has been shown to be significantly longer in PD patients compared to healthy controls (with a median increase of 1.75 hours in PD patients) (Dutkiewicz et al, 2015;Knudsen et al, 2017). To this end, we tested whether DHPPA (100 µM) could affect the muscle contractility in the ileum.…”

Section: -(34-dihydroxyphenyl)propionic Acid Elicits An Inhibitory mentioning

confidence: 99%

“…Importantly, chronic idiopathic constipation is associated with SI motor abnormalities in the esophagus, stomach, jejunum and ileum (Panagamuwa et al, 1994;Van Der Sijp et al, 1993) and patients with constipation have a longer SI transit time compared to controls (Van Der Sijp et al, 1993). Only recently, SI dysfunction in PD was studied showing that the transit time in the SI was significantly longer in PD patients compared to healthy controls (HC) (Dutkiewicz et al, 2015;Knudsen et al, 2017). Using wireless electromagnetic capsules, the SI transit time was reported to be significantly higher in PD patients (400 min; n=22) compared to HC (295 min, n=15) (Knudsen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Gut bacterial deamination of residual levodopa medication for Parkinson’s disease

Kessel

Jong

Winkel

et al. 2020

Preprint

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24Parkinson's disease is associated with gastrointestinal tract dysfunction, where constipation is reported 25 as the most common gastrointestinal symptom. Aromatic bacterial metabolites are attracting 26 considerable attention due to their implication on gut homeostasis and host's physiology. Clostridium 27 sporogenes is a key contributor to the production of these bioactive metabolites in the human gut. Here, 28we show that C. sporogenes effectively deaminate non-proteinogenic aromatic amino acids, such as 29 levodopa, the main treatment in Parkinson's disease, and identify the aromatic aminotransferase 30 responsible for the deamination. The deaminated metabolite from levodopa, 3-(3,4-dihydroxyphenyl) 31propionic acid, is detected in fecal samples of Parkinson's disease patients on levodopa medication, 32 elicits an inhibitory effect on gut motility. Overall, this study underpins the importance of the metabolic 33 pathways of the gut microbiome involved in drug metabolism not only to preserve drug effectiveness, 34 but also to avoid potential side effects of bacterial breakdown products of the unabsorbed residue of 35 medication. 36 37Recently, small intestinal microbiota have been implicated in the interference with levodopa drug 54 availability (van Kessel et al., 2019;Maini Rekdal et al., 2019). Early in vivo studies showed that ~90% 55 of levodopa is transported to the circulatory system (Bianchine et al., 1972;Morgan, 1971; Sasahara et 56 al., 1981), leaving a ~10% non-absorbed fraction of residual levodopa that can act as substrate for other 57 bacterial species associated with the lower, more anaerobic regions of the GI-tract (Goldin et al., 1973). 58Such bacterial-residual drug interaction might act as bioactive metabolites with an impact on gut 59 homeostasis. 60 PD is often associated with non-motor symptoms especially of the gastrointestinal (GI) tract. GI-tract 61 dysfunction such as constipation, drooling and swallowing disorders occur frequently in PD patients, 62 especially constipation, which is reported in 80-90% of the PD patients (Fasano et al., 2015). in the esophagus, stomach, jejunum and ileum (Panagamuwa et al., 1994; Van Der Sijp et al., 1993) and 65 patients with constipation have a longer SI transit time compared to controls (Van Der Sijp et al., 1993). 66Only recently, SI dysfunction in PD was studied observing that the transit time in the SI was significantly 67 longer in PD patients compared to healthy controls (Dutkiewicz et al., 2015; Knudsen et al., 2017). 68Using wireless electromagnetic capsules, the median small intestinal transit time observed was 69 significantly increased between PD patients (400 min; n=22) and healthy controls (295 min, n=15) 70 (Knudsen et al., 2017). 71This study unravels the aminotransferase responsible for initiating the deamination pathway involved in 72 the transamination of (among others) levodopa and shows that C. sporogenes can effectively deaminate 73 levodopa to 3-(3,4-dihydroxyphenyl) propionic acid through the same pathway as the other ar...

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Small intestine dysfunction in Parkinson’s disease

Cited by 39 publications

References 13 publications

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

Stool Immune Profiles Evince Gastrointestinal Inflammation in Parkinson's Disease

Gut bacterial deamination of residual levodopa medication for Parkinson’s disease

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