Intrahepatic microbes govern liver immunity by programming NKT cells.

The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined. Here, we showed a liver microbiome in mice and humans that is distinct from that of the gut and is enriched in Proteobacteria. It undergoes dynamic alterations with age and is influenced by the environment and host physiology. Fecal microbial transfer experiments revealed that the liver microbiome is populated from the gut in a highly selective manner. Hepatic immunity is dependent on the microbiome, specifically the bacteroidetes species. Targeting bacteroidetes with oral antibiotics reduced hepatic immune cells by approximately 90%, prevented antigen-presenting cell (APC) maturation, and mitigated adaptive immunity. Mechanistically, our findings are consistent with presentation of bacteroidetes-derived glycosphingolipids to NKT cells promoting CCL5 signaling, which drives hepatic leukocyte expansion and activation, among other possible host-microbe interactions. Collectively, we reveal a microbial/glycosphingolipid/NKT/CCL5 axis that underlies hepatic immunity.

A Mindfulness-Based Intervention to Alleviate Stress From Discrimination Among Young Sexual and Gender Minorities of Color: Protocol for a Pilot Optimization Trial.

BACKGROUND: Young sexual and gender minorities (SGMs) of color may face unique experiences of discrimination based on their intersectional positions (eg, discrimination based on both racial or ethnic identity and sexual identity). Emerging evidence suggests that mindfulness practices may reduce stress from discrimination and improve overall well-being among young SGM. Moreover, the omnipresence of smartphone access among racial or ethnic and sexual minority communities provides a method through which to administer mindfulness-based interventions among young SGMs of color. OBJECTIVE: This paper outlines the protocol of the Optimizing a Daily Mindfulness Intervention to Reduce Stress from Discrimination among Young Sexual and Gender Minorities of Color (REDUCE) study, a pilot optimization trial of a smartphone-based mindfulness intervention that was developed in conjunction with the Healthy Minds Program (HMP) with the aim of reducing stress from discrimination among young SGMs. METHODS: In total, 80 young (ages 18-29 years) SGMs of color will be enrolled in the study. The HMP is a self-guided meditation practice, and participants will be randomized to either a control condition or an intervention that uses a neuroscience-based approach to mindfulness. We will use the multiphase optimization strategy to assess which combination of mindfulness interventions is the most effective at reducing stress from discrimination among young SGMs of color. A combination of mindfulness-based meditation intervention components will be examined, comprising mindfulness-based practices of awareness, connection, and purpose. Awareness refers to the practice of self-awareness, which reduces the mind's ability to be distracted and instead be present in the moment. Connection refers to the practice of connection with oneself and others and emphasizes on empathy and compassion with oneself and others. Purpose encourages goal-making in accordance with one's values and management of behavior in accordance with these goals. In addition, we will assess the feasibility and acceptability of the HMP application among young SGMs of color. RESULTS: The REDUCE study was approved by the Institutional Review Board of New York University, and recruitment and enrollment began in the winter of 2021. We expect to complete enrollment by the summer of 2022. The results will be disseminated via social media, journal articles, abstracts, or presentations, as well as to participants, who will be given the opportunity to provide feedback to the researchers. CONCLUSIONS: This optimization trial is designed to test the efficacy, feasibility, and acceptability of implementing an application-based, mindfulness-based intervention to reduce stress from discrimination and improve well-being among young SGMs of color. Evidence from this study will assist in the creation of a sustainable, culturally relevant mobile app-based mindfulness intervention to reduce stress from discrimination among young SGMs of color. TRIAL REGISTRATION: Clinicaltrials.gov NCT05131360; https://clinicaltrials.gov/ct2/show/NCT05131360. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35593.