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

• Main Authors: Dobbs R, Charlett André, Dobbs Sylvia M, Weller Clive, A Ibrahim Mohammad A, Iguodala Owens, Smee Cori, Plant J, Lawson Andrew J, Taylor David, Bjarnason Ingvar
• Format: Article
• Language: English
• Published: BMC 2012-10-01
• Series: Gut Pathogens
• Subjects: Pathogenesis of Parkinson’s disease; <it>Helicobacter</it>; Small intestinal bacterial overgrowth; Blood leukocytes; Natural-killer; T-helper; Neutrophils; Hypokinesia; Rigidity; Tremor
• Online Access: http://www.gutpathogens.com/content/4/1/12

<p>Abstract</p> <p>Background</p> <p>Following <it>Helicobacter pylori</it> 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 <it>Helicobacter</it> keeps SIBO at bay.</p> <p>Methods</p> <p>In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of <it>Helicobacter</it> 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.</p> <p>Results</p> <p>Of 51 IP-probands, 36 had current or past <it>Helicobacter</it> 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 <it>Helicobacter</it>-positivity (OR 0.20 (95% CI 0.04, 0.99), p<0.05).</p> <p>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, <it>p</it>=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 <it>Helicobacter</it> 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 <it>Helicobacter</it>-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).</p> <p>Conclusion</p> <p>We propose a rigidity-associated subordinate pathway, flagged by a higher natural-killer count, tempered by a higher T-helper, against which <it>Helicobacter</it> protects by keeping SIBO at bay.</p>