Open Access Research

Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study

R John Dobbs123, André Charlett14, Sylvia M Dobbs123*, Clive Weller1, Mohammad A A Ibrahim5, Owens Iguodala2, Cori Smee2, J Malcolm Plant2, Andrew J Lawson6, David Taylor12 and Ingvar Bjarnason3

Author Affiliations

1 Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK

2 The Maudsley Hospital, Denmark Hill, London, SE5 8AZ, UK

3 Gastroenterology, King’s College Hospital, Bessemer Rd, London, SE5 9PJ, UK

4 Statistics Unit, Health Protection Agency, 61 Colindale Avenue, London, NW9 5EQ, UK

5 Clinical Immunology, King’s College Hospital, Bessemer Rd, London, SE5 9PJ, UK

6 Laboratory of Gastrointestinal Pathogens, Health Protection Agency, London, NW9 5EQ, UK

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Gut Pathogens 2012, 4:12  doi:10.1186/1757-4749-4-12

Published: 19 October 2012

Abstract

Background

Following Helicobacter pylori eradication in idiopathic parkinsonism (IP), hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO) is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay.

Methods

In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy) and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose). We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t½ therapy.

Results

Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before). Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests) during surveillance (2.8 years). Hydrogen-breath-test-positivity was associated inversely with Helicobacter-positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05).

In 38 patients (untreated (17) or on stable long-t½ IP-medication), the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85) mm, 54 (3, 104) mm.s-1, 89 (2, 177) Nm.10-3, per 100 cells.μl-1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics). T-helper count was inversely associated with flexor-rigidity before (p=0.01) and after adjustment for natural-killer count (-36(-63, -10) Nm.10-3 per 100 cells.μl-1, p=0.007). Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01). Effect-sizes were independent of IP-medication, and not masked by including 13 patients receiving levodopa (except natural-killer count on flexor-rigidity). Cellular associations held after allowing for potentially confounding effect of hydrogen-breath-test or Helicobacter status. Moreover, additional reduction in stride and speed (68 (24, 112) mm & 103 (38, 168) mm.s-1, each p=0.002) was seen with Helicobacter-positivity. Hydrogen-breath-test-positivity, itself, was associated with higher natural-killer and T-helper counts, lower neutrophils (p=0.005, 0.02 & 0.008).

Conclusion

We propose a rigidity-associated subordinate pathway, flagged by a higher natural-killer count, tempered by a higher T-helper, against which Helicobacter protects by keeping SIBO at bay.

Keywords:
Pathogenesis of Parkinson’s disease; Helicobacter; Small intestinal bacterial overgrowth; Blood leukocytes; Natural-killer; T-helper; Neutrophils; Hypokinesia; Rigidity; Tremor