Foregut microbiome in development of esophageal adenocarcinoma

Esophageal adenocarcinoma (EA), the type of cancer linked to heartburn due to gastroesophageal reflux diseases (GERD), has increased six fold in the past 30 years. This cannot currently be explained by the usual environmental or by host genetic factors. EA is the end result of a sequence of GERD-related diseases, preceded by reflux esophagitis (RE) and Barrett’s esophagus (BE). Preliminary studies by Pei and colleagues at NYU on elderly male veterans identified two types of microbiotas in the esophagus. Patients who carry the type II microbiota are >15 fold likely to have esophagitis and BE than those harboring the type I microbiota. In a small scale study, we also found that 3 of 3 cases of EA harbored the type II biota. The findings have opened a new approach to understanding the recent surge in the incidence of EA. 

Our long-term goal is to identify the cause of GERD sequence. The hypothesis to be tested is that changes in the foregut microbiome are associated with EA and its precursors, RE and BE in GERD sequence. We will conduct a case control study to demonstrate the microbiome disease association in every stage of GERD sequence, as well as analyze the trend in changes in the microbiome along disease progression toward EA, by two specific aims. Aim 1 is to conduct a comprehensive population survey of the foregut microbiome and demonstrate its association with GERD sequence. Furthermore, spatial relationship between the esophageal microbiota and upstream (mouth) and downstream (stomach) foregut microbiotas as well as temporal stability of the microbiome-disease association will also be examined. Aim 2 is to define the distal esophageal metagenome and demonstrate its association with GERD sequence. Detailed analyses will include pathway-disease and gene-disease associations. Archaea, fungi and viruses, if identified, also will be correlated with the diseases. A significant association between the foregut microbiome and GERD sequence, if demonstrated, will be the first step for eventually testing whether an abnormal microbiome is required for the development of the sequence of phenotypic changes toward EA. If EA and its precursors represent a microecological disease, treating the cause of GERD might become possible, for example, by normalizing the microbiota through use of antibiotics, probiotics, or prebiotics. Causative therapy of GERD could prevent its progression and reverse the current trend of increasing incidence of EA

Perinatal Mental Health During the COVID-19 Pandemic: Evidence for Heightened Distress in Pregnant Women Highlights the Need for Novel Interventions

This manuscript reports on a sample of 641 pregnant women surveyed in spring 2020, during the first wave of the COVID-19 pandemic when social distancing was at its peak in the United States. Expectant mothers described elevated psychological distress, perceived stress, loneliness, and many behavioral changes. More than half of the women in the sample endorsed depressive symptoms above clinical threshold and two-thirds reported clinically significant anxiety, with average scores for depression, anxiety, and stress more than a standard deviation higher than those measured pre-pandemic. Given this early evidence for heightened distress, treatment options that can be targeted to support perinatal women and comply with social distancing guidelines are needed. The final sections of this paper highlight the promising role of telehealth modalities and discuss specific interventions, such as Interpersonal Therapy, that may be particularly useful in treating perinatal women in the wake of the COVID-19 pandemic. Public Significance: The COVID-19 pandemic has had sweeping effects on perinatal mental health, which in turn has wide-ranging impacts for maternal, child, and family well-being. This paper describes treatment approaches that may ameliorate the pandemic’s impact