Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites

Cao, Yanyan; Oh, Joonseok; Xue, Mengzhao; Huh, Won Jae; Wang, Jiawei; González-Hernández, Jaime A.; Rice, Tyler; Martinez, Brian; Song, Dong‐Ping; Crawford, Jason M.; Herzon, Seth B.; Palm, Noah W.

doi:10.1126/science.abm3233

Cited by 128 publications

(64 citation statements)

References 71 publications

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“…Among these, we notably observed enrichment of Morganella morganii . This species has recently been reported to produce indolamines, which have genotoxic properties and could promote mutations that facilitate CRC metastasis [ 56 ].…”

Section: Discussionmentioning

confidence: 99%

Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer

Luu

Lagishetty

et al. 2023

Nutrients

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Colorectal cancer (CRC) is associated with alterations of the fecal and tissue-associated microbiome. Preclinical models support a pathogenic role of the microbiome in CRC, including in promoting metastasis and modulating antitumor immune responses. To investigate whether the microbiome is associated with lymph node metastasis and T cell infiltration in human CRC, we performed 16S rRNA gene sequencing of feces, tumor core, tumor surface, and healthy adjacent tissue collected from 34 CRC patients undergoing surgery (28 fecal samples and 39 tissue samples). Tissue microbiome profiles—including increased Fusobacterium—were significantly associated with mesenteric lymph node (MLN) involvement. Fecal microbes were also associated with MLN involvement and accurately classified CRC patients into those with or without MLN involvement. Tumor T cell infiltration was assessed by immunohistochemical staining of CD3 and CD8 in tumor tissue sections. Tumor core microbiota, including members of the Blautia and Faecalibacterium genera, were significantly associated with tumor T cell infiltration. Abundance of specific fecal microbes including a member of the Roseburia genus predicted high vs. low total and cytotoxic T cell infiltration in random forests classifiers. These findings support a link between the microbiome and antitumor immune responses that may influence prognosis of locally advanced CRC.

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Section: Discussionmentioning

confidence: 99%

Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer

Luu

Lagishetty

et al. 2023

Nutrients

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“…Indolimines were produced by the bacteria M. morganii. 91 In the azoxymethane/dextran sulfate sodium colon cancer mice, tumor burden was increased by M. morganii , but not by a mutant of M. morganii unable to produce indolimines. Indolimines-producing M. morganii exacerbated colon tumorigenesis in gnotobiotic mice, as well.…”

Section: Mechanistic/molecular Bases Of Diet-microbial Interactions I...mentioning

confidence: 96%

Microbiome and Diet in Colon Cancer Development and Treatment

Kato

Sun

2023

Cancer J

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Diet plays critical roles in defining our immune responses, microbiome, and progression of human diseases. With recent progress in sequencing and bioinformatic techniques, increasing evidence indicates the importance of diet-microbial interactions in cancer development and therapeutic outcome. Here, we focus on the epidemiological studies on diet-bacterial interactions in the colon cancer. We also review the progress of mechanistic studies using the experimental models. Finally, we discuss the limits and future directions in the research of microbiome and diet in cancer development and therapeutic outcome. Now, it is clear that microbes can influence the efficacy of cancer therapies. These research results open new possibilities for the diagnosis, prevention, and treatment of cancer. However, there are still big gaps to apply these new findings to the clinical practice.

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“…[56][57][58] Aside from damaging the DNA, both colibactin and indolimine can increase the permeability of the gut barrier, facilitating microbial translocation from the GI tract into host tissues. [59][60][61][62][63] In addition, colibactin and indolimine were demonstrated to activate bacteriophages in gut microbes, likely increasing the abundance of bacteriophageresistant tryptophan decarboxylase-expressing commensals and the levels of endogenous hallucinogens. 64,65 Notably, patients with schizophrenia were recently reported to exhibit altered oropharyngeal bacteriophages (phageome), connecting this disorder to microbial genotoxin-induced DNA damage.…”

Section: Microbial Genotoxins and Spimentioning

confidence: 99%

Microbiota-derived psychedelics: Lessons from COVID-19

Sfera¹,

Hazan²,

Kozlakidis³

et al. 2023

Adv Clin Exp Med

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Emil Kraepelin believed that dementia praecox, the disorder we now call schizophrenia, was caused by the brain being poisoned with toxins generated in other parts of the body, especially the mouth, intestine or genitals. In this regard, Kraepelin hinted at the microbiome and conceptualized microbial molecules as drivers of severe psychiatric illness. However, it was not until the coronavirus disease (COVID-19) pandemic that Kraepelin's paradigm gained traction, particularly because this virus was associated with both gut barrier disruption and new-onset psychosis. Likewise, despite numerous studies linking severe psychiatric illness to genomic damage and dysfunctional DNA repair, this pathogenetic mechanism was underappreciated before the COVID-19 pandemic. The use of the psychotomimetic anesthetic, ketamine, for treatment-resistant depression has reawakened the interest in endogenous serotonergic hallucinogens, especially tryptamine and N,N-dimethyltryptamine (DMT), which are beneficial for depression but associated with psychosis. In this editorial, we take a closer look at the role of the microbiome in psychopathology, attempting to answer 2 questions: 1. Why may psychosis-predisposing serotonergic hallucinogens alleviate depression? 2. Are microbiota-derived psychedelics part of an inbuilt antidepressant system similar to endogenous opioids?

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Commensal microbiota from patients with inflammatory bowel disease produce genotoxic metabolites

Cited by 128 publications

References 71 publications

Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer

Fecal and Tissue Microbiota Are Associated with Tumor T-Cell Infiltration and Mesenteric Lymph Node Involvement in Colorectal Cancer

Microbiome and Diet in Colon Cancer Development and Treatment

Microbiota-derived psychedelics: Lessons from COVID-19

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