Neuroprotective effects of short-chain fatty acids in MPTP induced mice model of Parkinson's disease

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and how they contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of SCFAs, inflammatory factors, and zonulin in stool. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are distinct in PD and are sex-dependent. This study revealed potential alterations in microbiota-host interactions and links between earlier PD onset and intestinal inflammatory responses and reduced SCFA levels, highlighting candidate molecules and pathways which may contribute to PD pathogenesis and clinical presentation and which warrant further investigation.

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Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease

10.21203/rs.3.rs-63018/v2 ◽

2021 ◽

Author(s):

Velma T Aho ◽

Madelyn Crawford Houser ◽

Pedro AB Pereira ◽

Jianjun Chang ◽

Knut Rudi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Disease Onset ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dependent Manner ◽

Chain Fatty Acids

Abstract Background Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD. Methods Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota. Results Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of stool SCFAs, inflammation, and zonulin. Certain relationships differed between patients and controls and by sex. Conclusions Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.

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Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease

10.21203/rs.3.rs-63018/v1 ◽

2020 ◽

Author(s):

Velma T Aho ◽

Madelyn Crawford Houser ◽

Pedro AB Pereira ◽

Jianjun Chang ◽

Knut Rudi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Disease Onset ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dependent Manner ◽

Chain Fatty Acids

Abstract Background: Previous studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and contribute to disease processes and symptoms remains uncertain. This study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.Methods: Stool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.Results: Calprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of stool SCFAs, inflammation, and zonulin. Certain relationships differed between patients and controls and by sex.Conclusions: Intestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.

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Plasma Short‐Chain Fatty Acids in Patients With Parkinson's Disease

Movement Disorders ◽

10.1002/mds.28016 ◽

2020 ◽

Vol 35 (6) ◽

pp. 1021-1027 ◽

Cited By ~ 3

Author(s):

Chaewon Shin ◽

Yunsook Lim ◽

Hyewon Lim ◽

Tae‐Beom Ahn

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Chain Fatty Acids

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Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease

10.1101/2020.06.15.20131011 ◽

2020 ◽

Author(s):

Velma T. E. Aho ◽

Madelyn C. Houser ◽

Pedro A. B. Pereira ◽

Jianjun Chang ◽

Knut Rudi ◽

...

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Intestinal Inflammation ◽

Disease Onset ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dependent Manner ◽

Chain Fatty Acids

AbstractBackgroundPrevious studies have reported that gut microbiota, permeability, short-chain fatty acids (SCFAs), and inflammation are altered in Parkinson’s disease (PD), but how these factors are linked and contribute to disease processes and symptoms remains uncertain.ObjectivesThis study sought to compare and identify associations among these factors in PD patients and controls to elucidate their interrelations and links to clinical manifestations of PD.MethodsStool and plasma samples and clinical data were collected from 55 PD patients and 56 controls. Levels of stool SCFAs and stool and plasma inflammatory and permeability markers were compared between patients and controls and related to one another and to the gut microbiota.ResultsCalprotectin was increased and SCFAs decreased in stool in PD in a sex-dependent manner. Inflammatory markers in plasma and stool were neither intercorrelated nor strongly associated with SCFA levels. Age at PD onset was positively correlated with SCFAs and negatively correlated with CXCL8 and IL-1β in stool. Fecal zonulin correlated positively with fecal NGAL and negatively with PD motor and non-motor symptoms. Microbiota diversity and composition were linked to levels of stool SCFAs, inflammation, and zonulin. These relationships differed somewhat between patients and controls and by sex.ConclusionsIntestinal inflammatory responses and reductions in fecal SCFAs occur in PD, are related to the microbiota and to disease onset, and are not reflected in plasma inflammatory profiles. Some of these relationships are PD- and sex-dependent. Alterations in microbiota-host interactions and links between intestinal inflammation and reduced SCFA levels and earlier PD onset warrant further investigation.

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Probiotik sebagai Pengatur Komposisi Gut microbiota dalam Menghambat Progresivitas Parkinson’s Disease

SCRIPTA SCORE Scientific Medical Journal ◽

10.32734/scripta.v3i1.4410 ◽

2021 ◽

Vol 3 (1) ◽

pp. 76-83

Author(s):

Ahmad Taufik Fadillah Zainal ◽

Andi Muh. Aunul Khaliq Gunawan ◽

A. Fitri Febrianty Fariadi

Keyword(s):

Parkinson’S Disease ◽

Fatty Acids ◽

Parkinson's Disease ◽

Gut Microbiota ◽

Therapeutic Target ◽

Short Chain Fatty Acids ◽

Alpha Synuclein ◽

Short Chain ◽

Chain Fatty Acids

Background: Parkinson's Disease (PD) is one of the most common neurodegenerative diseases at the age of 40-70 years. Disorders of the Gut-Microbiota-Brain Axis have been linked to bacterial metabolite products that play a role in the occurrence of neuroinflammation. Understanding precisely the role of the neuroinflammatory process in PD can lead to an understanding of how PD occurs and its relation to gut microbiota (GM). Objectives: To determine the effectiveness of probiotics as a therapeutic target to inhibit the progression of PD. Methods: Literature study method by collecting valid references regarding GM and PD and the relationship between them. Discussion: Evidence from in vivo trials using Alpha-Synuclease-Overexpressing (αSyn) mice reported that Dysbiosis GM can cause inflammation by activating microglia cells and increasing proinflammatory cytokines modulated by metabolite products of Short Chain Fatty Acids (SCFAs) which lead to the occurrence of alpha-Synuclein aggregation and leads to the progression of PD. One of the microbes that have decreased the number of Dysbiosis GM is Lactobacillus rhamnous GG, which has a neuroprotective role in inhibiting the progression of PD. Microbiota-targeted interventions using the probiotic L-GG method have shown a positive effect on inhibiting PD progression. Conclusion: GM dysbiosis caused by PD has a pathway that can increase the progression of PD. This can be used as a therapeutic target, microbial composition engineering with the method of giving L-GG probiotics to be a solution in inhibiting the progression of PD by restoring the neuroprotective effect of L-GG. Keywords: alpha-Synuclein (αSyn), Gut Microbiota (GM), Lactobacillus rhamnous GG (L-GG), Parkinson's Disease (PD), Short Chain Fatty Acids (SCFAs) Latar Belakang: Penyakit Parkinson (Parkinson’s Disease/PD) adalah salah satu penyakit neurodegeneratif yang paling banyak terjadi pada usia 40-70 tahun. Dewasa kini, gangguan pada Gut-Microbiota-Brain Axis telah dihubungkan dengan produk metabolit bakteri yang berperan pada terjadinya neuroinflamasi. Memahami secara tepat peranan dari proses neuroinflamasi pada Parkinson Disease (PD) dapat membawa pemahaman terhadap bagaimana PD timbul dan kaitannya dengan mikroba usus (Gut Microbiota/GM). Tujuan: Untuk mengetahui efektivitas probiotik sebagai target terapi untuk menghambat progresivitas PD. Metode: Literature reviewini disusun menggunakan metode studi pustaka dengan mengumpulkan referensi yang valid mengenai GM dan PD serta hubungan antar keduanya. Pembahasan: Bukti uji coba in vivo menggunakan tikus Alpha-Synuclease-Overexpressing (ASO) dilaporkan bahwa Dysbiosis Gut Microbiota dapat menyebabkan terjadinya inflamasi dengan mekanisme pengaktifan sel mikroglia dan peningkatan sitokin proinflamasi yang dimodulasi oleh produk metabolit Short Chain Fatty Acids (SCFAs) yang mengarahkan pada terjadinya agregasi alpha-Synuclein (αSyn) dan berujung pada progresivitas PD. Salah satu mikroba yang mengalami penurunan jumlah pada Dysbiosis Gut Microbiota adalah Lactobacillus rhamnous GG (L-GG), yang memiliki peran neuroprotektif dalam menghambat progresivitas PD. Intervensi berbasis Microbiota-targeted dengan metode penggunaan probiotik L-GG telah menunjukkan efek positif pada penghambatan progresivitas PD. Kesimpulan: Dysbiosis GM memiliki jalur yang mampu meningkatkan progresivitas dari penyakit parkinson. Hal ini mampu dimanfaatkan sebagai target terapi, rekayasa komposisi mikroba dengan metode pemberian probiotik L-GG menjadi solusi dalam menghambat progresivitas PD dengan mengembalikan efek neuroprotektif dari L-GG. Kata Kunci: alpha-Synuclein (αSyn), Gut Microbiota(GM), Lactobacillus rhamnous GG (L-GG), Parkinson Disease (PD), Short Chain Fatty Acids (SCFAs)

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