The antitumour effects of caloric restriction are mediated by the gut microbiome

Mao, Yuqin; Huang, Jiating; Zhang, Shilong; Kong, Chao; Li, Zhanming; Jing, Hui; Chen, Huiling; Kong, Chao‐Yue; Huang, Shenghui; Cai, Pei-Ran; Han, Bing; Wang, Li‐Shun

doi:10.1038/s42255-022-00716-4

Cited by 42 publications

(24 citation statements)

References 39 publications

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“…Current research focuses on developing targeted therapies that regulate microbiota mechanisms involved in cancer metastasis, such as fecal microbiota transplantation (FMT) [ 81 ], prebiotics [ 82 ], dietary changes [ 83 ], and antibiotics [ 84 ]. Recent studies have shown that caloric restriction (CR) can inhibit tumor growth in mice through a mechanism dependent on intestinal flora, but this inhibition is diminished in the presence of antibiotic depletion of intestinal flora, while bifidobacteria supplementation can restore the antitumor effects of CR, significantly inhibiting primary tumor growth and reducing metastatic burden [ 85 ]. These findings suggest that the microbiome may serve as a biomarker for cancer metastasis and offer potential therapeutic approaches for clinical application.…”

Section: Discussionmentioning

confidence: 99%

Current Understanding of Microbiomes in Cancer Metastasis

Liu

Luo

Wen

et al. 2023

Cancers

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Cancer has been the first killer that threatens people’s lives and health. Despite recent improvements in cancer treatment, metastasis continues to be the main reason for death from cancer. The functions of microbiome in cancer metastasis have been studied recently, and it is proved that microbiome can influence tumor metastasis, as well as positive or negative responses to therapy. Here, we summarize the mechanisms of microorganisms affecting cancer metastasis, which include epithelial-mesenchymal transition (EMT), immunity, fluid shear stress (FSS), and matrix metalloproteinases (MMPs). This review will not only give a further understanding of relationship between microbiome and cancer metastasis, but also provide a new perspective for the microbiome’s application in cancer metastasis prevention, early detection, and treatment.

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Section: Discussionmentioning

confidence: 99%

Current Understanding of Microbiomes in Cancer Metastasis

Liu

Luo

Wen

et al. 2023

Cancers

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“…Having demonstrated a broad enhancement in the functional capacity of memory T cells from mice on DR, we next assessed the potential role of acetate in this response. Several elegant studies have shown that acetate can directly enhance T cell function ( 9 , 43 – 46 ). However, supplementing memory mice fed ad libitum with acetate was not sufficient to enhance memory T cell function ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Recent evidence has revealed that fluctuating or reduced dietary intake can positively shape host immunity by enhancing the function of various immune cells ( 1 , 2 , 6 – 8 ). For instance, we and others have shown that dietary restriction (DR) enhances the function of T cells, which improves host survival in contexts of infection and cancer ( 6 , 7 , 9 ). As mammals evolved throughout periods of food scarcity, these results support the idea that restricted or fluctuating food availability could represent a “beneficial stressor” that promotes optimal host fitness.…”

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confidence: 99%

“…The microbiota possesses a remarkable ability to reconfigure and alter its function in response to physiological alterations, a phenomenon believed to promote host resilience ( 20 , 23 – 25 ). For example, restricting dietary intake has been shown to remodel the microbiota in a manner that directly improves host metabolism, prevents cancer, and mitigates aberrant tissue inflammation ( 9 , 26 , 27 ). Based on the closely intertwined relationship between nutrition and the microbiota, commensal adaptation to nutritional fluctuations would be expected to contribute to immune regulation.…”

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confidence: 99%

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Microbiota configuration determines nutritional immune optimization

Han,

Stacy,

Corral

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Mild or transient dietary restriction (DR) improves many aspects of health and aging. Emerging evidence from us and others has demonstrated that DR also optimizes the development and quality of immune responses. However, the factors and mechanisms involved remain to be elucidated. Here, we propose that DR-induced optimization of immunological memory requires a complex cascade of events involving memory T cells, the intestinal microbiota, and myeloid cells. Our findings suggest that DR enhances the ability of memory T cells to recruit and activate myeloid cells in the context of a secondary infection. Concomitantly, DR promotes the expansion of commensal Bifidobacteria within the large intestine, which produce the short-chain fatty acid acetate. Acetate conditioning of the myeloid compartment during DR enhances the capacity of these cells to kill pathogens. Enhanced host protection during DR is compromised when Bifidobacteria expansion is prevented, indicating that microbiota configuration and function play an important role in determining immune responsiveness to this dietary intervention. Altogether, our study supports the idea that DR induces both memory T cells and the gut microbiota to produce distinct factors that converge on myeloid cells to promote optimal pathogen control. These findings suggest that nutritional cues can promote adaptation and co-operation between multiple immune cells and the gut microbiota, which synergize to optimize immunity and protect the collective metaorganism.

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“…Caloric restriction inhibits growth of subcutaneous MC38 tumor formation in female mice. Using 16S rRNA sequencing of the gut microbiome, Mao et al [25 ▪ ] reported enrichment of Bifidobacterium during 40% caloric restriction, lack of protection by caloric restriction in microbiota-depleted mice, and finally rescue of the antitumor effect by Bifidobacterium bifidum administration.…”

Section: Mechanisms Of Caloric Restriction Effects In Cancer Modelsmentioning

confidence: 99%

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

Arends

2023

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Different forms of caloric restriction for patients with cancer are widely advertised in lay circles, based mainly on promising preclinical experiments, while evidence from clinical trials is still preliminary. This review aims to present physiological responses to fasting and update knowledge on recently accumulated evidence from preclinical models and clinical trials. Recent findings Like other mild stressors, caloric restriction induces hormetic changes in healthy cells, which increase the tolerance to subsequent more severe stressors. While protecting healthy tissues, caloric restriction sensitizes malignant cells to toxic interventions because of their deficiencies in hormetic mechanisms, especially control of autophagy. In addition, caloric restriction may activate anticancer-directed immune cells and deactivate suppressive cells, thus increasing immunosurveillance and anticancer cytotoxicity. These effects may combine to increase the effectivity of cancer treatments while limiting adverse events. Though evidence obtained from preclinical models is promising, clinical trials in cancer patients so far have been preliminary. In clinical trials it will remain essential to avoid inducing or aggravating malnutrition. Summary Based on physiology and evidence from preclinical models, caloric restriction is a promising candidate as a potential combination partner for clinical anticancer treatment. However, large randomized clinical trials investigating effects on clinical outcome in patients with cancer are still lacking.

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The antitumour effects of caloric restriction are mediated by the gut microbiome

Cited by 42 publications

References 39 publications

Current Understanding of Microbiomes in Cancer Metastasis

Current Understanding of Microbiomes in Cancer Metastasis

Microbiota configuration determines nutritional immune optimization

Caloric restriction and fasting-mimicking diets in the treatment of cancer patients

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