Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy?

Dong, Yue Jiao; Zhang, Kexin; Wei, Jingge; Wang, Xin; Hou, Huiqin; Wu, Jingyi; Li, Tianyu; Wang, Bangmao; Cao, Hailong

doi:10.3389/fimmu.2023.1158200

Cited by 13 publications

(4 citation statements)

References 137 publications

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“…The abundance of Bacteroidetes has been associated with the induction of IFN-γ producing T cells to protect the host from bacterial infections [ 68 ]. In addition, this phylum is highly recognized for its ability to produce short-chain fatty acids known to promote the migration of neutrophils to areas of inflammation and the differentiation of B cells into plasma cells [ 69 , 70 , 71 ]. On the other hand, Enterococcus has been associated with lesions in the oral cavity, such as periodontitis, and in promoting colorectal cancer [ 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer

Díaz-Rivera,

Rodríguez-Rivera,

Meléndez-Vázquez

et al. 2024

Cancers

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The United States is suffering from an epidemic associated with high-risk strains of the Human Papillomavirus (HPV) predominantly responsible for the development of head and neck squamous cell carcinoma (HNSCC). Treatment with immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand PD-L1 has shown poor efficacy in HNSCC patients, observing only a 20–30% response. Therefore, biological marker identification associated with PD-1 blockade response is important to improve prognosis and define novel therapeutics for HNSCC patients. Therapy response was associated with increased frequencies of activated CD27+T cells, activated CD79a+ B cells, antigen-presenting CD74+ dendritic and B cells, and PD-L1+ and PD-L2+ myeloid-derived suppressor cells (MDSCs). The oral microbiota composition differed significantly in mice bearing tongue tumors and treated with anti-PD-1. A higher abundance of Allobaculum, Blautia, Faecalibacterium, Dorea, or Roseburia was associated with response to the therapy. However, an increase in Enterococcus was attributed to tongue tumor-bearing non-responding mice. Our findings indicate that differences in immune phenotypes, protein expression, and bacterial abundance occur as mice develop tongue tumors and are treated with anti-PD-1. These results may have a clinical impact as specific bacteria and immune phenotype could serve as biomarkers for treatment response in HNSCC.

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Section: Discussionmentioning

confidence: 99%

Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer

Díaz-Rivera,

Rodríguez-Rivera,

Meléndez-Vázquez

et al. 2024

Cancers

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“…In recent years, several studies have investigated the mechanisms of butyrate at the cellular and systemic levels and its potential therapeutic use in different pathologies [ 53 , 54 ]. Whether HF patients may benefit from the adjuvant treatment with butyrate will be confirmed with large designed clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota and Derived Short-Chain Fatty Acids Are Linked to Evolution of Heart Failure Patients

Modrego,

Ortega-Hernández,

Goirigolzarri

et al. 2023

IJMS

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There is a lack of direct evidence regarding gut microbiota dysbiosis and changes in short-chain fatty acids (SCFAs) in heart failure (HF) patients. We sought to assess any association between gut microbiota composition, SCFA production, clinical parameters, and the inflammatory profile in a cohort of newly diagnosed HF patients. In this longitudinal prospective study, we enrolled eighteen newly diagnosed HF patients. At admission and after 12 months, blood samples were collected for the assessment of proinflammatory cytokines, monocyte populations, and endothelial dysfunction, and stool samples were collected for analysis of gut microbiota composition and quantification of SCFAs. Twelve months after the initial HF episode, patients demonstrated improved clinical parameters and reduced inflammatory state and endothelial dysfunction. This favorable evolution was associated with a reversal of microbiota dysbiosis, consisting of the increment of health-related bacteria, such as genus Bifidobacterium, and levels of SCFAs, mainly butyrate. Furthermore, there was a decrease in the abundance of pathogenic bacteria. In vitro, fecal samples collected after 12 months of follow-up exhibited lower inflammation than samples collected at admission. In conclusion, the favorable progression of HF patients after the initial episode was linked to the reversal of gut microbiota dysbiosis and increased SCFA production, particularly butyrate. Whether restoring butyrate levels or promoting the growth of butyrate-producing bacteria could serve as a complementary treatment for these patients deserves further studies.

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“… 283 , 284 The gut microbiota, which is mediated by SCFAs, can potentiate the antitumor activity of CD8 + T cells, thereby influencing the efficacy of tumor immunotherapy both in vitro and in vivo. 285 Metabolic and epigenetic reprogramming enables pentanoate and butyrate to enhance the effectiveness of cancer immunotherapy by boosting the antitumor activity of antigen-specific cytotoxic T lymphocytes and ROR1-targeting chimeric antigen receptor (CAR)-T cells. 286 Inosine is another important metabolite produced by the microbiome and is closely associated with immunotherapy.…”

Section: Diet Changes the Gut Microbiome In Conjunction With Antitumo...mentioning

confidence: 99%

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

Xiao,

Gong,

et al. 2024

Sig Transduct Target Ther

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Diet, serving as a vital source of nutrients, exerts a profound influence on human health and disease progression. Recently, dietary interventions have emerged as promising adjunctive treatment strategies not only for cancer but also for neurodegenerative diseases, autoimmune diseases, cardiovascular diseases, and metabolic disorders. These interventions have demonstrated substantial potential in modulating metabolism, disease trajectory, and therapeutic responses. Metabolic reprogramming is a hallmark of malignant progression, and a deeper understanding of this phenomenon in tumors and its effects on immune regulation is a significant challenge that impedes cancer eradication. Dietary intake, as a key environmental factor, can influence tumor metabolism. Emerging evidence indicates that dietary interventions might affect the nutrient availability in tumors, thereby increasing the efficacy of cancer treatments. However, the intricate interplay between dietary interventions and the pathogenesis of cancer and other diseases is complex. Despite encouraging results, the mechanisms underlying diet-based therapeutic strategies remain largely unexplored, often resulting in underutilization in disease management. In this review, we aim to illuminate the potential effects of various dietary interventions, including calorie restriction, fasting-mimicking diet, ketogenic diet, protein restriction diet, high-salt diet, high-fat diet, and high-fiber diet, on cancer and the aforementioned diseases. We explore the multifaceted impacts of these dietary interventions, encompassing their immunomodulatory effects, other biological impacts, and underlying molecular mechanisms. This review offers valuable insights into the potential application of these dietary interventions as adjunctive therapies in disease management.

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Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy?

Cited by 13 publications

References 137 publications

Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer

Immune and Microbial Signatures Associated with PD-1 Blockade Sensitivity in a Preclinical Model for HPV+ Oropharyngeal Cancer

Gut Microbiota and Derived Short-Chain Fatty Acids Are Linked to Evolution of Heart Failure Patients

Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential

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