Abstract
Hookworm infects over 400 million people globally and causes gastrointestinal morbidity, yet its physiological effects remain poorly defined. Controlled human hookworm infection is also being explored as a therapy for gut diseases. We performed an exploratory study to evaluate the impact of experimental Necator americanus infection on gastrointestinal transit, motility, and luminal pH in 10 healthy adults (mean age 41 years, 60% female) infected with 30 larvae via skin application. Assessments using the SmartPillTM Wireless Motility Capsule were performed at baseline, week 6 (acute infection), and week 24 or 48 (chronic infection). Parameters included gastric emptying time, small bowel and colonic transit, whole gut transit, intraluminal pressures, contraction frequency, motility index, and segmental pH, analyzed with paired t-tests or ANOVA. All participants developed patent infections. No significant differences were observed in gastric emptying, small bowel, colonic, or whole gut transit times, nor in motility indices or contraction frequencies. However, during acute infection, duodenal (6.14 ± 0.19 vs. 5.80 ± 0.24, p<0.05) and small bowel pH (6.96 ± 0.37 vs. 6.50 ± 0.37, p<0.05) were significantly reduced compared with baseline, normalizing by the chronic phase. No other significant pH alterations were detected. Thus, these data suggest that controlled N. americanus infection in healthy adults induces a transient reduction in duodenal and small-intestinal pH without affecting gastrointestinal transit or motility. This acidification may contribute to acute-phase symptoms and nutrient malabsorption in endemic settings, while the absence of sustained motility disturbance supports the safety of controlled hookworm infection for therapeutic investigation.