Biology subjects

Ajami, N.

Publications and source records attributed to Ajami, N..

3 recordsLinked to original sources

bioRxiv2026

Tryptophan degradation by intestinal Bacteroides induces anti-tumor immunity and limits melanoma growth

Defining mechanisms used by gut microbiota to control anti-tumor immunity may offer novel therapeutic modalities. Here, we demonstrate that Bacteroides rodentium and closely related Bacteroides uniformis species induce anti-tumor immunity and limit melanoma development when colonized in either germ-free (GF) mice, mice with a complex microbiome, or WT mice. Enhanced CD8+ T cell infiltration seen in tumors of mice harboring B. rodentium coincided with increased expression of immune-stimulating pathways and activation of bone marrow-derived dendritic cells that were co-cultured with the B. rodentium secretome. Metabolomic analyses of cecal samples from GF mice colonized with Altered Shedlar Flora (ASF) plus B. rodentium revealed lower tryptophan levels than in ASF-colonized controls, and WT mice fed a tryptophan-deficient diet exhibited inhibition of melanoma development. In silico genomic reconstruction of metabolic pathways revealed that both B. rodentium and B. uniformis harbor tryptophanase A (TnaA) and aromatic amino transferase (ArAT) genes, both of which function in tryptophan degradation. Administration of a B. uniformis harboring TnaA mutant failed to inhibit melanoma growth in gnotobiotic mice. Notably, administration of indoles, but not kynurenines, also effectively inhibited melanoma development, increasing immune cell infiltration into the tumors. Correspondingly, levels of bacterially encoded tryptophan-degrading enzymes were higher in cohorts of melanoma patients responding to immune checkpoint blockade. These findings highlight a novel mechanism of anti-tumor immunity and tumor growth inhibition dependent on the tryptophan degradation products, indoles, produced by intestinal Bacteroides species.

cancer biology↗

bioRxiv2024

Intratumoral Microbiome of Adenoid Cystic Carcinomas and Comparison with other Head and Neck Cancers

BackgroundAdenoid cystic carcinoma (ACC) is a rare, slow growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. MethodsWe investigated the intratumoral microbiome of 50 ACC tumors and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within ACC and explore potential associations between the bacterial community structure, patients clinical characteristics, and tumor molecular features obtained through RNA sequencing. ResultsBacterial composition in ACC displayed significant differences compared to adjacent normal salivary tissue and exhibited diverse levels of species richness. We identified two main microbial subtypes within ACC: oral-like and gut-like. Oral-like microbiomes, characterized by higher diversity and abundance of genera like Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with the less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and in head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with more diverse microbiome, less aggressive tumor phenotype, and better survival. Conversely, gut-like microbiomes in ACC, featuring low diversity and colonization by gut mucus layer-degrading species like Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival, regardless of other clinical and molecular factors. Furthermore, this association positively correlated with tumor cell biosynthesis of glycan-based cell membrane components. ConclusionsOur study uncovers specific intratumoral oral genera as potential pan-cancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. These findings highlight the pivotal role of the intratumoral microbiome in influencing ACC prognosis and disease biology.

microbiology↗

bioRxiv2020

Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

BackgroundA diverse and abundant gut microbiome can improve cancer patients treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. Materials and MethodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species. ConclusionAfter CRT, the gut microbiomes diversity tends to return to baseline levels, but its structure and composition remain significantly altered. These changes should be considered when designing studies to analyze the gut microbiome as a predictive or prognostic biomarker in patients who receive pelvic CRT for gynecologic cancers.

cancer biology↗