Alcohol shifts gut microbial networks and ameliorates a murine model of neuroinflammation in a sex-specific pattern.

Alcohol is a widely consumed dietary component by patients with autoimmune neuroinflammatory diseases, but current evidence on the effects of alcohol in these conditions is confounding. Epidemiological studies suggest moderate consumption of alcohol may be protective in some autoimmune diseases; however, this correlation has not been directly investigated. Here, we characterize the effects of moderate-dose alcohol in a model system of autoimmune neuroinflammation, experimental autoimmune encephalomyelitis (EAE). Male and female C57BL/6J mice were fed a 2.6% alcohol or isocaloric diet for 3 wk prior to MOG35-55 EAE induction. Surprisingly, alcohol-fed males experienced significantly greater disease remission compared to alcohol-fed females and control-fed counterparts. We observed a male-specific decrease in microglial density in alcohol-consuming animals in cervical and thoracic spinal cord in late-stage disease. In the gut, alcohol diet resulted in several sex-specific alterations in key microbiota known for their regulatory immune roles, including Turicibacter, Akkermansia, Prevotella, and Clostridium Using a correlation network modeling approach, we identified unique bacterial modules that are significantly enriched in response to treatment and sex, composed of Clostridial taxa and several Firmicutes known to be protective in EAE. Together, these data demonstrate the potential of alcohol to significantly alter the course of autoimmunity differentially in males and females via effects on gut bacterial networks and support further need to evaluate dose and sex-specific alcohol effects in multiple sclerosis (MS) and other autoimmune neuroinflammatory conditions.

SARS-CoV-2 Humoral Immune Responses in Convalescent Individuals Over 12 Months Reveal Severity-Dependent Antibody Dynamics.

Background: Understanding the kinetics and longevity of antibody responses to SARS-CoV-2 is critical to informing strategies toward reducing Coronavirus disease 2019 (COVID-19) reinfections, and improving vaccination and therapy approaches. Methods: We evaluated antibody titers against SARS-CoV-2 nucleocapsid (N), spike (S), and receptor binding domain (RBD) of spike in 98 convalescent participants who experienced asymptomatic, mild, moderate or severe COVID-19 disease and in 17 non-vaccinated, non-infected controls, using four different antibody assays. Participants were sampled longitudinally at 1, 3, 6, and 12 months post-SARS-CoV-2 positive PCR test. Findings: Increasing acute COVID-19 disease severity correlated with higher anti-N and anti-RBD antibody titers throughout 12 months post-infection. Anti-N and anti-RBD titers declined over time in all participants, with the exception of increased anti-RBD titers post-vaccination, and the decay rates were faster in hospitalized compared to non-hospitalized participants. <50% of participants retained anti-N titers above control levels at 12 months, with non-hospitalized participants falling below control levels sooner. Nearly all hospitalized and non-hospitalized participants maintained anti-RBD titers above controls for up to 12 months, suggesting longevity of protection against severe reinfections. Nonetheless, by 6 months, few participants retained >50% of their 1-month anti-N or anti-RBD titers. Vaccine-induced increases in anti-RBD titers were greater in non-hospitalized relative to hospitalized participants. Early convalescent antibody titers correlated with age, but no association was observed between Post-Acute Sequelae of SARS-CoV-2 infection (PASC) status or acute steroid treatment and convalescent antibody titers. Interpretation: Hospitalized participants developed higher anti-SARS-CoV-2 antibody titers relative to non-hospitalized participants, a difference that persisted throughout 12 months, despite the faster decline in titers in hospitalized participants. In both groups, while anti-N titers fell below control levels for at least half of the participants, anti-RBD titers remained above control levels for almost all participants over 12 months, demonstrating generation of long-lived antibody responses known to correlate with protection from severe disease across COVID-19 severities. Overall, our findings contribute to the evolving understanding of COVID-19 antibody dynamics. Funding: Austin Public Health, NIAAA, Babson Diagnostics, Dell Medical School Startup.

Alcohol as friend or foe in autoimmune diseases: a role for gut microbiome?

Alcohol is well known for promoting systemic inflammation and aggravating multiple chronic health conditions. Thus, alcohol may also be expected to serve as a risk factor in autoimmune diseases. However, emerging data from human and animal studies suggest that alcohol may in fact be protective in autoimmune diseases. These studies point toward alcohol's complex dose-dependent relationship in autoimmune diseases as well as potential modulation by duration and type of alcohol consumption, cultural background and sex. In this review, we will explore alcohol's pro- and anti-inflammatory properties in human and animal autoimmune diseases, including autoimmune diabetes, thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, experimental autoimmune encephalomyelitis and multiple sclerosis. We will also discuss potential mechanisms of alcohol's anti-inflammatory effects mediated by the gut microbiome.