Exploratory study characterizing gastrointestinal physiological changes during controlled human hookworm infection

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 <i>Necator americanus</i> infection on gastrointestinal transit, motility, and luminal pH in 10 healthy adults (mean age 41 yr, 60% females) infected with 30 larvae via skin application. Assessments using the SmartPill Wireless Motility Capsule were performed at baseline, <i>week 6</i> (acute infection), and <i>week 24</i> or <i>48</i> (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 <i>t</i> 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, <i>P</i> < 0.05) and small bowel pH (6.96 ± 0.37 vs. 6.50 ± 0.37, <i>P</i> < 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 <i>N. americanus</i> 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, whereas the absence of sustained motility disturbance supports the safety of controlled hookworm infection for therapeutic investigation.<b>NEW & NOTEWORTHY</b> This exploratory study using SmartPill technology found that controlled hookworm infection in healthy adults caused a transient drop in duodenal and small-intestinal pH during the acute phase, but no lasting changes in gut motility or transit. The findings, the first of their kind in humans, suggest that the physiological effects of controlled doses of hookworm are subtle and short-lived, offering reassurance for therapeutic trials while highlighting a potential mechanism for symptoms and malabsorption in endemic regions.