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Introduction: Disparities in incidence and outcome of rectal cancer are multifactorial in etiology but may be due, in part, to differences in gut microbiome composition. We used serial robust statistical approaches to assess baseline gut microbiome composition in a diverse cohort of patients with rectal cancer receiving definitive treatment. Methods: Microbiome composition was compared by age at diagnosis (< 50 vs ≥ 50 years), race and ethnicity (White Hispanic vs non-Hispanic), and response to therapy. Alpha diversity was assessed using the Shannon, Chao1, and Simpson diversity measures. Beta diversity was explored using both Bray-Curtis dissimilarity and Aitchison distance with principal coordinate analysis. To minimize false-positive findings, we used two distinct methods for differential abundance testing: LinDA and MaAsLin2 (all statistics two-sided, Benjamini-Hochberg corrected false discovery rate < 0.05). Results: Among 64 patients (47% White Hispanic) with median age 51 years, beta diversity metrics showed significant clustering by race and ethnicity (p < 0.001 by both metrics) and by onset (Aitchison p = 0.022, Bray-Curtis p = 0.035). White Hispanic patients had enrichment of bacterial family Prevotellaceae (LinDA fold change 5.32, MaAsLin2 fold change 5.11, combined adjusted p = 0.0007). No significant differences in microbiome composition were associated with neoadjuvant therapy response. Conclusion: We identified distinct gut microbiome signatures associated with race and ethnicity and age of onset in a diverse cohort of patients undergoing definitive treatment for rectal cancer. [ABSTRACT FROM AUTHOR]

Multiple host and microbial factors dictate whether Candida albicans can colonize the mammalian gastrointestinal tract. In this issue of Cell Host & Microbe , Savage et al. demonstrate that restoration of intestinal epithelial hypoxia is sufficient to restore Candida albicans colonization resistance, even when other Candida inhibitory effectors remain depleted. [ABSTRACT FROM AUTHOR]

Candida albicans is a ubiquitous fungus in the human gut microbiome as well as a prevalent cause of opportunistic mucosal and systemic disease. There is currently little understanding, however, as to how crosstalk between C. albicans and the host regulates colonization of this key niche. Here, we performed expression profiling on ileal and colonic tissues in germ-free mice colonized with C. albicans to define the global response to this fungus. We reveal that Duox2 and Duoxa2 , encoding dual NADPH oxidase activity, are upregulated in both the ileum and colon, and that induction requires the C. albicans yeast-hyphal transition and the hyphal-specific toxin candidalysin. Hosts lacking the IL-17 receptor failed to upregulate Duox2/Duoxa2 in response to C. albicans , while addition of IL-17A to colonoids induced these genes together with the concomitant production of hydrogen peroxide. To directly define the role of Duox2/Duoxa2 in fungal colonization, antibiotic-treated mice lacking intestinal DUOX2 activity were evaluated for C. albicans colonization and host responses. Surprisingly, loss of DUOX2 function reduced fungal colonization at extended time points (>17 days colonization) and increased the proportion of hyphal cells in the gut. IL-17A levels were also elevated in C. albicans -colonized mice lacking functional DUOX2 highlighting cross-regulation between this cytokine and DUOX2. Together, these experiments reveal novel links between fungal cells, candidalysin toxin and the host IL-17-DUOX2 axis, and that a complex interplay between these factors regulates C. albicans filamentation and colonization in the gut.