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Impaired gut barrier integrity and reduced colonic expression of free fatty acid receptors in patients with Parkinson's disease.

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Title: Impaired gut barrier integrity and reduced colonic expression of free fatty acid receptors in patients with Parkinson's disease.
Authors: Liao, Peng-Hsiang (AUTHOR), Tung, Hsiao-Yen (AUTHOR), Lim, Wee Shin (AUTHOR), Jang, Jyh-Shing Roger (AUTHOR), Li, Hsun (AUTHOR), Shun, Chia-Tung (AUTHOR), Chiu, Han-Mo (AUTHOR), Wu, Ming-Shiang (AUTHOR), Lin, Chin-Hsien (AUTHOR)
Source: Neurological Sciences. Nov2024, Vol. 45 Issue 11, p5297-5307. 11p.
Subjects: Short-chain fatty acids, Parkinson's disease, Free fatty acids, Tight junctions, Movement disorders
Abstract: Background: Altered gut metabolites, especially short-chain fatty acids (SCFAs), in feces and plasma are observed in patients with Parkinson's disease (PD). Objective: We aimed to investigate the colonic expression of two SCFA receptors, free fatty acid receptor (FFAR)2 and FFAR3, and gut barrier integrity in patients with PD and correlations with clinical severity. Methods: In this retrospective study, colonic biopsy specimens were collected from 37 PD patients and 34 unaffected controls. Of this cohort, 31 participants (14 PD, 17 controls) underwent a series of colon biopsies. Colonic expression of FFAR2, FFAR3, and the tight junction marker ZO-1 were assayed by immunofluorescence staining. The You Only Look Once (version 8, YOLOv8) algorithm was used for automated detection and segmentation of immunostaining signal. PD motor function was assessed with the Movement Disorder Society (MDS)-Unified Parkinson's Disease Rating Scale (UPDRS), and constipation was assessed using Rome-IV criteria. Results: Compared with controls, PD patients had significantly lower colonic expression of ZO-1 (p < 0.01) and FFAR2 (p = 0.01). On serial biopsy, colonic expression of FFAR2 and FFAR3 was reduced in the pre-motor stage before PD diagnosis (both p < 0.01). MDS-UPDRS motor scores did not correlate with colonic marker levels. Constipation severity negatively correlated with colonic ZO-1 levels (r = -0.49, p = 0.02). Conclusions: Colonic expression of ZO-1 and FFAR2 is lower in PD patients compared with unaffected controls, and FFAR2 and FFAR3 levels decline in the pre-motor stage of PD. Our findings implicate a leaky gut phenomenon in PD and reinforce that gut metabolites may contribute to the process of PD. [ABSTRACT FROM AUTHOR]
Copyright of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Impaired gut barrier integrity and reduced colonic expression of free fatty acid receptors in patients with Parkinson&#39;s disease.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Liao%2C+Peng-Hsiang%22&quot;&gt;Liao, Peng-Hsiang&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Tung%2C+Hsiao-Yen%22&quot;&gt;Tung, Hsiao-Yen&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lim%2C+Wee+Shin%22&quot;&gt;Lim, Wee Shin&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Jang%2C+Jyh-Shing+Roger%22&quot;&gt;Jang, Jyh-Shing Roger&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Li%2C+Hsun%22&quot;&gt;Li, Hsun&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Shun%2C+Chia-Tung%22&quot;&gt;Shun, Chia-Tung&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Chiu%2C+Han-Mo%22&quot;&gt;Chiu, Han-Mo&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Wu%2C+Ming-Shiang%22&quot;&gt;Wu, Ming-Shiang&lt;/searchLink&gt; (AUTHOR)&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lin%2C+Chin-Hsien%22&quot;&gt;Lin, Chin-Hsien&lt;/searchLink&gt; (AUTHOR)
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Neurological+Sciences%22&quot;&gt;Neurological Sciences&lt;/searchLink&gt;. Nov2024, Vol. 45 Issue 11, p5297-5307. 11p.
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  Data: &lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Short-chain+fatty+acids%22&quot;&gt;Short-chain fatty acids&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Parkinson&#39;s+disease%22&quot;&gt;Parkinson&#39;s disease&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Free+fatty+acids%22&quot;&gt;Free fatty acids&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Tight+junctions%22&quot;&gt;Tight junctions&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;DE&quot; term=&quot;%22Movement+disorders%22&quot;&gt;Movement disorders&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Altered gut metabolites, especially short-chain fatty acids (SCFAs), in feces and plasma are observed in patients with Parkinson&#39;s disease (PD). Objective: We aimed to investigate the colonic expression of two SCFA receptors, free fatty acid receptor (FFAR)2 and FFAR3, and gut barrier integrity in patients with PD and correlations with clinical severity. Methods: In this retrospective study, colonic biopsy specimens were collected from 37 PD patients and 34 unaffected controls. Of this cohort, 31 participants (14 PD, 17 controls) underwent a series of colon biopsies. Colonic expression of FFAR2, FFAR3, and the tight junction marker ZO-1 were assayed by immunofluorescence staining. The You Only Look Once (version 8, YOLOv8) algorithm was used for automated detection and segmentation of immunostaining signal. PD motor function was assessed with the Movement Disorder Society (MDS)-Unified Parkinson&#39;s Disease Rating Scale (UPDRS), and constipation was assessed using Rome-IV criteria. Results: Compared with controls, PD patients had significantly lower colonic expression of ZO-1 (p &lt; 0.01) and FFAR2 (p = 0.01). On serial biopsy, colonic expression of FFAR2 and FFAR3 was reduced in the pre-motor stage before PD diagnosis (both p &lt; 0.01). MDS-UPDRS motor scores did not correlate with colonic marker levels. Constipation severity negatively correlated with colonic ZO-1 levels (r = -0.49, p = 0.02). Conclusions: Colonic expression of ZO-1 and FFAR2 is lower in PD patients compared with unaffected controls, and FFAR2 and FFAR3 levels decline in the pre-motor stage of PD. Our findings implicate a leaky gut phenomenon in PD and reinforce that gut metabolites may contribute to the process of PD. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Neurological Sciences is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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      – Type: doi
        Value: 10.1007/s10072-024-07641-2
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      – Code: eng
        Text: English
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      – SubjectFull: Short-chain fatty acids
        Type: general
      – SubjectFull: Parkinson's disease
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      – SubjectFull: Free fatty acids
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      – SubjectFull: Tight junctions
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              Text: Nov2024
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