Parkinson's Disease Medication Alters Small Intestinal Motility and Microbiota Composition in Healthy Rats.

Parkinson's disease (PD) is known to be associated with altered gastrointestinal function and microbiota composition. To date, the effect of PD medication on the gastrointestinal function and microbiota, at the site of drug absorption, the small intestine, has not been studied, although it may represent an important confounder in reported microbiota alterations observed in PD patients. To this end, healthy (non-PD) wild-type Groningen rats were employed and treated with dopamine, pramipexole (in combination with levodopa-carbidopa), or ropinirole (in combination with levodopa-carbidopa) for 14 sequential days. Rats treated with dopamine agonists showed a significant reduction in small intestinal motility and an increase in bacterial overgrowth in the distal small intestine. Notably, significant alterations in microbial taxa were observed between the treated and vehicle groups; analogous to the changes previously reported in human PD versus healthy control microbiota studies. These microbial changes included an increase in Lactobacillus and Bifidobacterium and a decrease in Lachnospiraceae and Prevotellaceae. Markedly, certain Lactobacillus species correlated negatively with levodopa levels in the systemic circulation, potentially affecting the bioavailability of levodopa. Overall, the study highlights a significant effect of PD medication intrinsically on disease-associated comorbidities, including gastrointestinal dysfunction and small intestinal bacterial overgrowth, as well as the gut microbiota composition. The results urge future studies to take into account the influence of PD medication per se when seeking to identify microbiota-related biomarkers for PD. IMPORTANCE Parkinson's disease (PD) is the second most common neurodegenerative disorder and is known to be associated with altered gastrointestinal function and microbiota composition. We previously showed that the gut bacteria harboring tyrosine decarboxylase enzymes interfere with levodopa, the main treatment for PD (S. P. van Kessel, A. K. Frye, A. O. El-Gendy, M. Castejon, A. Keshavarzian, G. van Dijk, and S. El Aidy, Nat Commun 10:310, 2019). Although PD medication could be an important confounder in the reported alterations, its effect, apart from the disease itself, on the microbiota composition or the gastrointestinal function at the site of drug absorption, the small intestine, has not been studied. The findings presented here show a significant impact of commonly prescribed PD medication on the small intestinal motility, small intestinal bacterial overgrowth, and microbiota composition, irrespective of the PD. Remarkably, we observed negative associations between bacterial species harboring tyrosine decarboxylase activity and levodopa levels in the systemic circulation, potentially affecting the bioavailability of levodopa. Overall, this study shows that PD medication is an important factor in determining gastrointestinal motility and, in turn, microbiota composition and may, partly, explain the differential abundant taxa previously reported in the cross-sectional PD microbiota human studies. The results urge future studies to take into account the influence of PD medication on gut motility and microbiota composition when seeking to identify microbiota-related biomarkers for PD.

Gut bacteria-derived 5-hydroxyindole is a potent stimulant of intestinal motility via its action on L-type calcium channels.

Microbial conversion of dietary or drug substrates into small bioactive molecules represents a regulatory mechanism by which the gut microbiota alters intestinal physiology. Here, we show that a wide variety of gut bacteria can metabolize the dietary supplement and antidepressant 5-hydroxytryptophan (5-HTP) to 5-hydroxyindole (5-HI) via the tryptophanase (TnaA) enzyme. Oral administration of 5-HTP results in detection of 5-HI in fecal samples of healthy volunteers with interindividual variation. The production of 5-HI is inhibited upon pH reduction in in vitro studies. When administered orally in rats, 5-HI significantly accelerates the total gut transit time (TGTT). Deciphering the underlying mechanisms of action reveals that 5-HI accelerates gut contractility via activation of L-type calcium channels located on the colonic smooth muscle cells. Moreover, 5-HI stimulation of a cell line model of intestinal enterochromaffin cells results in significant increase in serotonin production. Together, our findings support a role for bacterial metabolism in altering gut motility and lay the foundation for microbiota-targeted interventions.

The head start tobacco cessation initiative: using systems change to support staff identification and intervention for tobacco use in low-income families.

Tobacco use continues to be the leading cause of preventable illness and death in the United States. Remarkably, more than nine million preschool-aged children are exposed to secondhand smoke, resulting in increased rates of morbidity and mortality. Even more disturbing is that tobacco use is highest among people with the lowest levels of income and education. Thus, reaching these populations is a challenge facing tobacco control programs. This report describes an innovative pilot project implementing a systems change model that involves multiple stakeholders in integrating evidence-based cessation strategies into federal Head Start programs, which serve low-income adults and their children. The Tobacco Cessation Initiative was developed through a partnership between the American Legacy Foundation, the Mailman School of Public Health at Columbia University, and the Louisiana State University Health Sciences Center School of Public Health. The partnership developed guidelines to fit into the overall mission of Head Start by enabling participating sites to incorporate tobacco cessation identification and referral protocols into their existing infrastructures. This program allowed Head Start sites to incorporate, into their existing family services, protocols for user identification and referral; build partnerships with groups supporting tobacco cessation; link families to cessation services; and educate families about risks associated with exposure to secondhand smoke. Applying system strategies in non-clinical settings such as Head Start offers a way to improve the health and quality of life of preschool children at the highest risk for exposure to secondhand smoke.

Seven-year patterns in US cigar use epidemiology among young adults aged 18-25 years: a focus on race/ethnicity and brand.

OBJECTIVES: We examined patterns in cigar use among young adults, aged 18-25 years, focusing on race/ethnicity and brand. METHODS: We conducted a secondary data analysis of cross-sectional waves of the National Survey on Drug Use and Health, 2002-2008, using multivariate logistic regression to assess time trends in past 30 days cigar use, past 30 days use of a "top 5" cigar brand, cigar use intensity, and age at first cigar use. RESULTS: Cigar use has increased among White non-Hispanic men aged 18 to 25 years, from 12.0% in 2002 to 12.7% in 2008. Common predictors of all outcomes included male gender and past 30 days use of cigarettes, marijuana, and blunts. Additional predictors of past 30 days cigar and "top 5" brand use included younger age, non-Hispanic Black or White race, lower income, and highest level of risk behavior. College enrollment predicted intensity of use and "top 5" brand use. CONCLUSIONS: Recent legislative initiatives have changed how cigars are marketed and may affect consumption. National surveys should include measures of cigar brand and little cigar and cigarillo use to improve cigar use estimates.