Faculty Bibliography

The gut-brain axis plays an important role in maintaining homeostasis. Many intrinsic and extrinsic factors influence signaling along this axis, modulating the function of both the enteric and central nervous systems. More recently the role of the microbiome as an important factor in modulating gut-brain signaling has emerged and the concept of a microbiota-gut-brain axis has been established. In this review, we highlight the role of this axis in modulating enteric and central nervous system function and how this may impact disorders such as irritable bowel syndrome and disorders of mood and affect. We examine the overlapping biological constructs that underpin these disorders with a special emphasis on the neurotransmitter serotonin, which plays a key role in both the gastrointestinal tract and in the brain. Overall, it is clear that although animal studies have shown much promise, more progress is necessary before these findings can be translated for diagnostic and therapeutic benefit in patient populations.

Parkinson's disease (PD) is a common neurodegenerative disorder characterized primarily by motor and non-motor gastrointestinal (GI) deficits. GI symptoms' including compromised intestinal barrier function often accompanies altered gut microbiota composition and motor deficits in PD. Therefore, in this study, we set to investigate the role of gut microbiota and epithelial barrier dysfunction on motor symptom generation using a rotenone-induced mouse model of PD. We found that while six weeks of 10 mg/kg of chronic rotenone administration by oral gavage resulted in loss of tyrosine hydroxylase (TH) neurons in both germ-free (GF) and conventionally raised (CR) mice, the decrease in motor strength and coordination was observed only in CR mice. Chronic rotenone treatment did not disrupt intestinal permeability in GF mice but resulted in a significant change in gut microbiota composition and an increase in intestinal permeability in CR mice. These results highlight the potential role of gut microbiota in regulating barrier dysfunction and motor deficits in PD.

Gastrointestinal (GI) comorbidities are common in individuals with mood and behavioral dysfunction. Similarly, patients with GI problems more commonly suffer from co-morbid psychiatric diagnoses. Although the central and enteric nervous systems (CNS and ENS, respectively) have largely been studied separately, there is emerging interest in factors that may contribute to disease states involving both systems. There is strong evidence to suggest that serotonin may be an important contributor to these brain-gut conditions. Serotonin has long been recognized for its critical functions in CNS development and function. The majority of the body's serotonin, however, is produced in the GI tract, where it plays key roles in ENS development and function. Further understanding of the specific impact that enteric serotonin has on brain-gut disease may lay the foundation for the creation of novel therapeutic targets. This review summarizes the current data focusing on the important roles that serotonin plays in ENS development and motility, with a focus on novel aspects of serotonergic signaling in medical conditions in which CNS and ENS co-morbidities are common, including autism spectrum disorders and depression.

We report a case of a newly recognized primary immunodeficiency due to biallelic mutations in CARMIL2 manifesting as an actinic prurigo-like photodermatitis, allergic diathesis and recurrent infections in a child. We present this case to highlight a rare phenotype seen in this T-cell immunodeficiency and provide an overview of other dermatologic manifestations among published reports of this condition.

While there are numerous medical comorbidities associated with ASD, gastrointestinal (GI) issues have a significant impact on quality of life for these individuals. Recent findings continue to support the relationship between the gut microbiome and both GI symptoms and behavior, but the heterogeneity within the autism spectrum requires in-depth clinical characterization of these clinical cohorts. Large, diverse, well-controlled studies in this area of research are still needed. Although there is still much to discover about the brain-gut-microbiome axis in ASD, microbially mediated therapies, specifically probiotics and fecal microbiota transplantation have shown promise in the treatment of GI symptoms in ASD, with potential benefit to the core behavioral symptoms of ASD as well. Future research and clinical trials must increasingly consider complex phenotypes in ASD in stratification of large datasets as well as in design of inclusion criteria for individual therapeutic interventions.

Gastrointestinal disorders are one of the most common medical conditions that are comorbid with autism spectrum disorders. These comorbidities can cause greater severity in autism spectrum disorder symptoms, other associated clinical manifestations, and lower quality of life if left untreated. Clinicians need to understand how these gastrointestinal issues present and apply effective therapies. Effective treatment of gastrointestinal problems in autism spectrum disorder may result in marked improvements in autism spectrum disorder behavioral outcomes. This article discusses the gastrointestinal disorders commonly associated with autism spectrum disorders, how they present, and studied risk factors.