Diet Quality and the Fecal Microbiota in Adults in the American Gut Project.

BACKGROUND: The Dietary Guidelines for Americans advises on dietary intake to meet nutritional needs, promote health, and prevent diseases. Diet affects the intestinal microbiota and is increasingly linked to health. It is vital to investigate the relationships between diet quality and the microbiota to better understand the impact of nutrition on human health. OBJECTIVES: This study aimed to investigate the differences in fecal microbiota composition in adults from the American Gut Project based on their adherence to the Dietary Guidelines for Americans. METHODS: This study was a cross-sectional analysis of the 16S sequencing and food frequency data of a subset of adults (n = 432; age = 18-60 y; 65% female, 89% white) participating in the crowdsourced American Gut Project. The Healthy Eating Index-2015 assessed the compliance with Dietary Guideline recommendations. The cohort was divided into tertiles based on Healthy Eating Index-2015 scores, and differences in taxonomic abundances and diversity were compared between high and low scorers. RESULTS: The mean Total Score for low-scoring adults (58.1 ± 5.4) was comparable with the reported score of the average American adult (56.7). High scorers for the Total Score and components related to vegetables, grains, and dairy had greater alpha diversity than low scorers. High scorers in the fatty acid component had a lower alpha diversity than low scorers (95% CI: 0.35, 1.85). A positive log-fold difference in abundance of plant carbohydrate-metabolizing taxa in the families Lachnospiraceae and Ruminococcaceae was observed in high-scoring tertiles for Total Score, vegetable, fruit, and grain components (Benjamini-Hochberg; q < 0.05). CONCLUSIONS: Adults with greater compliance to the Dietary Guidelines demonstrated higher diversity in their fecal microbiota and greater abundance of bacteria capable of metabolizing complex carbohydrates, providing evidence on how Dietary Guidelines support the gut microbiota.

Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination.

Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency.

Exploiting albumin as a mucosal vaccine chaperone for robust generation of lung-resident memory T cells.

Tissue-resident memory T cells (TRMs) can profoundly enhance mucosal immunity, but parameters governing TRM induction by vaccination remain poorly understood. Here, we describe an approach exploiting natural albumin transport across the airway epithelium to enhance mucosal TRM generation by vaccination. Pulmonary immunization with albumin-binding amphiphile conjugates of peptide antigens and CpG adjuvant (amph-vaccines) increased vaccine accumulation in the lung and mediastinal lymph nodes (MLNs). Amph-vaccines prolonged antigen presentation in MLNs over 2 weeks, leading to 25-fold increased lung-resident T cell responses over traditional immunization and enhanced protection from viral or tumor challenge. Mimicking such prolonged exposure through repeated administration of soluble vaccine revealed that persistence of both antigen and adjuvant was critical for optimal TRM induction, mediated through T cell priming in MLNs after prime, and directly in the lung tissue after boost. Thus, vaccine persistence strongly promotes TRM induction, and amph-conjugates may provide a practical approach to achieve such kinetics in mucosal vaccines.