Stability of Methylphenidate under Various pH Conditions in the Presence or Absence of Gut Microbiota.

Methylphenidate is one of the most widely used oral treatments for attention-deficit/hyperactivity disorder (ADHD). The drug is mainly absorbed in the small intestine and has low bioavailability. Accordingly, a high interindividual variability in terms of response to the treatment is known among ADHD patients treated with methylphenidate. Nonetheless, very little is known about the factors that influence the drug's absorption and bioavailability. Gut microbiota has been shown to reduce the bioavailability of a wide variety of orally administered drugs. Here, we tested the ability of small intestinal bacteria to metabolize methylphenidate. In silico analysis identified several small intestinal bacteria to harbor homologues of the human carboxylesterase 1 enzyme responsible for the hydrolysis of methylphenidate in the liver into the inactive form, ritalinic acid. Despite our initial results hinting towards possible bacterial hydrolysis of the drug, up to 60% of methylphenidate is spontaneously hydrolyzed in the absence of bacteria and this hydrolysis is pH-dependent. Overall, our results indicate that the stability of methylphenidate is compromised under certain pH conditions in the presence or absence of gut microbiota.

Microbiota and gut neuropeptides: a dual action of antimicrobial activity and neuroimmune response.

The gut microbiota is comprised of a vast variety of microbes that colonize the gastrointestinal tract and exert crucial roles for the host health. These microorganisms, partially via their breakdown of dietary components, are able to modulate immune response, mood, and behavior, establishing a chemical dialogue in the microbiota-gut-brain interphase. Changes in the gut microbiota composition and functionality are associated with multiple diseases, in which altered levels of gut-associated neuropeptides are also detected. Gut neuropeptides are strong neuroimmune modulators; they mediate the communication between the gut microbiota and the host (including gut-brain axis) and have also recently been found to exert antimicrobial properties. This highlights the importance of understanding the interplay between gut neuropeptides and microbiota and their implications on host health. Here, we will discuss how gut neuropeptides help to maintain a balanced microbiota and we will point at the missing gaps that need to be further investigated in order to elucidate whether these molecules are related to neuropsychiatric disorders, which are often associated with gut dysbiosis and altered gut neuropeptide levels.