Helicobacter suis Is Associated With Mortality in Parkinson's Disease

Aisha D. Augustin; Antonella Savio; Amanda Nevel; Richard J. Ellis; Clive Weller; David Taylor; Rosalind M. Tucker; Mohammad A.A. Ibrahim; Ingvar Bjarnason; Sylvia M. Dobbs; R. John Dobbs; Andre Charlett

doi:10.3389/fmed.2019.00188

Helicobacter suis Is Associated With Mortality in Parkinson's Disease

Aisha D. Augustin, Antonella Savio, Amanda Nevel, Richard J. Ellis, Clive Weller, David Taylor, Rosalind M. Tucker, Mohammad A.A. Ibrahim, Ingvar Bjarnason, Sylvia M. Dobbs^*, R. John Dobbs, Andre Charlett

^*Corresponding author for this work

Statistics Unit

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Abstract

Helicobacter pylori has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized placebo-controlled trial, improved PD hypokinesia. Helicobacter species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers. Indeed, Helicobacter is causally-associated with gastric lymphoma. We have previously shown that the relative-frequency, H. suis to H. pylori, was 10-times greater in 60 PD-patients than in 256 controls. We now go on to evaluate the pathological significance of H. suis, detected in gastric-biopsy DNA-extracts by ureA-based species-specific qPCR, validated by amplicon sequencing. The methodology had been cross-validated by a carR-based PCR. The pathological significance is put in context of H. pylori detection [urea-breath-test (UBT) with biopsy-culture, and, if negative, PCR], and the potential reservoir in pigs. Here, we explore, in these 60 PD-patients, associations of H. suis status with all-cause-mortality, and with orthostatic cardiovascular and blood profiling. H. suis had been detected in 19 of the 60 PD-patients on one or more occasion, only two (with co-existent H. pylori) being UBT positive. We found that the hazard-of-death (age-at-diagnosis- and gender-adjusted) was 12 (95% CI 1,103) times greater (likelihood-ratio test, P = 0.005) with H. suis-positivity (6/19) than with negativity (2/40: one lost to follow-up). UBT-values did not influence the hazard. H. suis-positivity was associated with lower standing mean-arterial-pressure [6 (1, 11) mmHg], H. pylori-positivity having no effect. The lower total lymphocyte count with H. pylori-positivity [−8 (−1, −14) %] was not seen with H. suis, where T-cell counts were higher [24 (2, 52) %]. Regarding the potential zoonotic reservoir in the UK, Helicobacter-like-organism frequency was determined in freshly-slaughtered pigs, nature ascertained by sequencing. Organisms immunostaining for Helicobacter, with corkscrew morphology typical of non-H. pylori Helicobacter, were seen in 47% of 111 pig-antra. We conclude that H. suis is associated with all-cause-mortality in PD and has a potential zoonotic reservoir.

Original language	English
Article number	188
Journal	Frontiers in Medicine
Volume	6
DOIs	https://doi.org/10.3389/fmed.2019.00188
Publication status	Published - 28 Aug 2019

Bibliographical note

Funding Information:
Assays on microbial DNA extracted from human gastric biopsies, archived at Public Health England, had been carried out at Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinarian Medicine, Ghent University, Belgium, by Dr. Caroline Bleacher. This was part of her PhD studentship, joint between RD and SD, King's College London and Prof. Freddy Haesebrouck with Dr. Annemieke Smet, Ghent University. Funding. Our grateful thanks go to the Psychiatry Research Trust, London, the Cecil Pilkington Charitable Trust, and the Cyril Corden Trust. Thanks are also go to Louise Barton and the late Brian Newman, Richard and Diana Gloyn, Alex and Lyn Orr, and Jamie and Julia Korner for their generous donations through the Psychiatry Research Trust. RT's studentship was funded by a grant from UCB Pharma.

Keywords

Helicobacter pylori
Helicobacter suis
Parkinson's disease
all-cause mortality
pig reservoir

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10.3389/fmed.2019.00188

Cite this

@article{25dda550e60a473a9e1940a179062858,

title = "Helicobacter suis Is Associated With Mortality in Parkinson's Disease",

abstract = "Helicobacter pylori has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized placebo-controlled trial, improved PD hypokinesia. Helicobacter species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers. Indeed, Helicobacter is causally-associated with gastric lymphoma. We have previously shown that the relative-frequency, H. suis to H. pylori, was 10-times greater in 60 PD-patients than in 256 controls. We now go on to evaluate the pathological significance of H. suis, detected in gastric-biopsy DNA-extracts by ureA-based species-specific qPCR, validated by amplicon sequencing. The methodology had been cross-validated by a carR-based PCR. The pathological significance is put in context of H. pylori detection [urea-breath-test (UBT) with biopsy-culture, and, if negative, PCR], and the potential reservoir in pigs. Here, we explore, in these 60 PD-patients, associations of H. suis status with all-cause-mortality, and with orthostatic cardiovascular and blood profiling. H. suis had been detected in 19 of the 60 PD-patients on one or more occasion, only two (with co-existent H. pylori) being UBT positive. We found that the hazard-of-death (age-at-diagnosis- and gender-adjusted) was 12 (95% CI 1,103) times greater (likelihood-ratio test, P = 0.005) with H. suis-positivity (6/19) than with negativity (2/40: one lost to follow-up). UBT-values did not influence the hazard. H. suis-positivity was associated with lower standing mean-arterial-pressure [6 (1, 11) mmHg], H. pylori-positivity having no effect. The lower total lymphocyte count with H. pylori-positivity [−8 (−1, −14) %] was not seen with H. suis, where T-cell counts were higher [24 (2, 52) %]. Regarding the potential zoonotic reservoir in the UK, Helicobacter-like-organism frequency was determined in freshly-slaughtered pigs, nature ascertained by sequencing. Organisms immunostaining for Helicobacter, with corkscrew morphology typical of non-H. pylori Helicobacter, were seen in 47% of 111 pig-antra. We conclude that H. suis is associated with all-cause-mortality in PD and has a potential zoonotic reservoir.",

keywords = "Helicobacter pylori, Helicobacter suis, Parkinson's disease, all-cause mortality, pig reservoir",

author = "Augustin, {Aisha D.} and Antonella Savio and Amanda Nevel and Ellis, {Richard J.} and Clive Weller and David Taylor and Tucker, {Rosalind M.} and Ibrahim, {Mohammad A.A.} and Ingvar Bjarnason and Dobbs, {Sylvia M.} and Dobbs, {R. John} and Andre Charlett",

note = "Funding Information: Assays on microbial DNA extracted from human gastric biopsies, archived at Public Health England, had been carried out at Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinarian Medicine, Ghent University, Belgium, by Dr. Caroline Bleacher. This was part of her PhD studentship, joint between RD and SD, King's College London and Prof. Freddy Haesebrouck with Dr. Annemieke Smet, Ghent University. Funding. Our grateful thanks go to the Psychiatry Research Trust, London, the Cecil Pilkington Charitable Trust, and the Cyril Corden Trust. Thanks are also go to Louise Barton and the late Brian Newman, Richard and Diana Gloyn, Alex and Lyn Orr, and Jamie and Julia Korner for their generous donations through the Psychiatry Research Trust. RT's studentship was funded by a grant from UCB Pharma.",

year = "2019",

month = aug,

day = "28",

doi = "10.3389/fmed.2019.00188",

language = "English",

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T1 - Helicobacter suis Is Associated With Mortality in Parkinson's Disease

AU - Augustin, Aisha D.

AU - Savio, Antonella

AU - Nevel, Amanda

AU - Ellis, Richard J.

AU - Weller, Clive

AU - Taylor, David

AU - Tucker, Rosalind M.

AU - Ibrahim, Mohammad A.A.

AU - Bjarnason, Ingvar

AU - Dobbs, Sylvia M.

AU - Dobbs, R. John

AU - Charlett, Andre

N1 - Funding Information: Assays on microbial DNA extracted from human gastric biopsies, archived at Public Health England, had been carried out at Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinarian Medicine, Ghent University, Belgium, by Dr. Caroline Bleacher. This was part of her PhD studentship, joint between RD and SD, King's College London and Prof. Freddy Haesebrouck with Dr. Annemieke Smet, Ghent University. Funding. Our grateful thanks go to the Psychiatry Research Trust, London, the Cecil Pilkington Charitable Trust, and the Cyril Corden Trust. Thanks are also go to Louise Barton and the late Brian Newman, Richard and Diana Gloyn, Alex and Lyn Orr, and Jamie and Julia Korner for their generous donations through the Psychiatry Research Trust. RT's studentship was funded by a grant from UCB Pharma.

PY - 2019/8/28

Y1 - 2019/8/28

N2 - Helicobacter pylori has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized placebo-controlled trial, improved PD hypokinesia. Helicobacter species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers. Indeed, Helicobacter is causally-associated with gastric lymphoma. We have previously shown that the relative-frequency, H. suis to H. pylori, was 10-times greater in 60 PD-patients than in 256 controls. We now go on to evaluate the pathological significance of H. suis, detected in gastric-biopsy DNA-extracts by ureA-based species-specific qPCR, validated by amplicon sequencing. The methodology had been cross-validated by a carR-based PCR. The pathological significance is put in context of H. pylori detection [urea-breath-test (UBT) with biopsy-culture, and, if negative, PCR], and the potential reservoir in pigs. Here, we explore, in these 60 PD-patients, associations of H. suis status with all-cause-mortality, and with orthostatic cardiovascular and blood profiling. H. suis had been detected in 19 of the 60 PD-patients on one or more occasion, only two (with co-existent H. pylori) being UBT positive. We found that the hazard-of-death (age-at-diagnosis- and gender-adjusted) was 12 (95% CI 1,103) times greater (likelihood-ratio test, P = 0.005) with H. suis-positivity (6/19) than with negativity (2/40: one lost to follow-up). UBT-values did not influence the hazard. H. suis-positivity was associated with lower standing mean-arterial-pressure [6 (1, 11) mmHg], H. pylori-positivity having no effect. The lower total lymphocyte count with H. pylori-positivity [−8 (−1, −14) %] was not seen with H. suis, where T-cell counts were higher [24 (2, 52) %]. Regarding the potential zoonotic reservoir in the UK, Helicobacter-like-organism frequency was determined in freshly-slaughtered pigs, nature ascertained by sequencing. Organisms immunostaining for Helicobacter, with corkscrew morphology typical of non-H. pylori Helicobacter, were seen in 47% of 111 pig-antra. We conclude that H. suis is associated with all-cause-mortality in PD and has a potential zoonotic reservoir.

AB - Helicobacter pylori has been implicated in the pathogenesis of Parkinson's disease (PD). Its eradication, in a randomized placebo-controlled trial, improved PD hypokinesia. Helicobacter species zoonosis might explain excess mortality from PD and non-Hodgkin lymphoma in livestock, but not arable, farmers. Indeed, Helicobacter is causally-associated with gastric lymphoma. We have previously shown that the relative-frequency, H. suis to H. pylori, was 10-times greater in 60 PD-patients than in 256 controls. We now go on to evaluate the pathological significance of H. suis, detected in gastric-biopsy DNA-extracts by ureA-based species-specific qPCR, validated by amplicon sequencing. The methodology had been cross-validated by a carR-based PCR. The pathological significance is put in context of H. pylori detection [urea-breath-test (UBT) with biopsy-culture, and, if negative, PCR], and the potential reservoir in pigs. Here, we explore, in these 60 PD-patients, associations of H. suis status with all-cause-mortality, and with orthostatic cardiovascular and blood profiling. H. suis had been detected in 19 of the 60 PD-patients on one or more occasion, only two (with co-existent H. pylori) being UBT positive. We found that the hazard-of-death (age-at-diagnosis- and gender-adjusted) was 12 (95% CI 1,103) times greater (likelihood-ratio test, P = 0.005) with H. suis-positivity (6/19) than with negativity (2/40: one lost to follow-up). UBT-values did not influence the hazard. H. suis-positivity was associated with lower standing mean-arterial-pressure [6 (1, 11) mmHg], H. pylori-positivity having no effect. The lower total lymphocyte count with H. pylori-positivity [−8 (−1, −14) %] was not seen with H. suis, where T-cell counts were higher [24 (2, 52) %]. Regarding the potential zoonotic reservoir in the UK, Helicobacter-like-organism frequency was determined in freshly-slaughtered pigs, nature ascertained by sequencing. Organisms immunostaining for Helicobacter, with corkscrew morphology typical of non-H. pylori Helicobacter, were seen in 47% of 111 pig-antra. We conclude that H. suis is associated with all-cause-mortality in PD and has a potential zoonotic reservoir.

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KW - Helicobacter suis

KW - Parkinson's disease

KW - all-cause mortality

KW - pig reservoir

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U2 - 10.3389/fmed.2019.00188

DO - 10.3389/fmed.2019.00188

M3 - Article

AN - SCOPUS:85072739816

SN - 2296-858X

VL - 6

JO - Frontiers in Medicine

JF - Frontiers in Medicine

M1 - 188

ER -

Helicobacter suis Is Associated With Mortality in Parkinson's Disease

Abstract

Bibliographical note

Keywords

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