β-Hydroxybutyrate suppresses colorectal cancer

Dmitrieva-Posocco, Oxana; Wong, Andrea C.; Lundgren, Patrick; Golos, Aleksandra M; Descamps, Hélène C.; Dohnalová, Lenka; Cramer, Zvi; Tian, Ye; Yueh, Brian; Eskiocak, Onur; Egervári, Gábor; Lan, Yemin; Liu, Jinping; Fan, Jiaxin; Kim, Jihee; Madhu, Bhoomi; Schneider, Kai Markus; Khoziainova, Svetlana; Andreeva, Natalia; Wang, Qiaohong; Li, Ning; Furth, Emma E.; Bailis, Will; Kelsen, Judith R.; Hamilton, Kathryn E.; Kaestner, Klaus H.; Berger, Shelley L.; Epstein, Jonathan A.; Jain, Rajan; Li, Mingyao; Beyaz, Semir; Lengner, Christopher J.; Katona, Bryson W.; Grivennikov, Sergei I.; Thaiss, Christoph A.; Levy, Maayan

doi:10.1038/s41586-022-04649-6

Cited by 185 publications

(111 citation statements)

References 40 publications

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“… 331 Similarly, picropodophyllin, as an inhibitor of IGF-1R, stimulates the infiltration of intratumoral cytotoxic T lymphocytes (CTLs) but reduces Tregs to enhance the efficacy of chemoimmunotherapy with a combination of immunogenic chemotherapeutics and PD-1 antagonists. 138 KD is capable to suppress colorectal tumorigenesis, 353 and KD or oral 3-hydroxybutyrate supplementation re-establishes therapeutic responses to immune checkpoint inhibitors. 354 Mechanistically, ketone bodies profoundly impact human T-cell responses by markedly enhancing the capacity of CD4 + T cells, CD8 + T cells, and Tregs and augmenting the formation of memory T cells.…”

Section: Dietary Intervention In Tissue Health and Diseasementioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.

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Section: Dietary Intervention In Tissue Health and Diseasementioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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“…HOPX is a known regulator of differentiation lineages (Liu and Zhang, 2020) in various tissues, and sustains the reservoir of intestinal stem cells that can originate all intestinal epithelial compartments (Takeda et al ., 2011). Although the role of HOPX in CRC is controversial (Yamashita et al ., 2013; Dmitrieva-Posocco et al ., 2022), the assumption that its activation could contribute to the progression of a subset of aggressive tumors is in agreement with the observation that high expression of HOPX is significantly associated with bad prognosis in CRC (overall survival Log Rank p value 8.6 × 10 −3 in the TCGA colorectal cohort, Figure 4D and (Liu and Zhang, 2020)).…”

Section: Resultsmentioning

confidence: 99%

CONNECTOR, fitting and clustering of longitudinal data to reveal a new risk stratification system

Pernice

Sirovich

Grassi

et al. 2022

Preprint

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The transition from the evaluation of a single time point to the examination of the entire dynamic evolution of a system is possible only in the presence of the proper framework. The strong variability of dynamic evolution makes the definition of an explanatory procedure for data fitting and data clustering challenging. Here we present CONNECTOR, a data-driven framework able to analyze and inspect longitudinal data in a straightforward and revealing way. When used to analyze tumor growth kinetics over time in 1599 patient-derived xenograft (PDX) growth curves from ovarian and colorectal cancers, CONNECTOR allowed the aggregation of time-series data through an unsupervised approach in informative clusters. Through the lens of a new perspective of mechanism interpretation, CONNECTOR shed light onto novel model aggregations and identified unanticipated molecular associations with response to clinically approved therapies.

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“…Butyrate can also by metabolized to β-hydroxybutyrate via the intermediate acetoacetate. A recent study elegantly demonstrated that β-hydroxybutyrate reduced colonic crypt cell proliferation and suppressed intestinal tumor growth via recruiting GPR109A and the transcriptional regulator homeodomain-only protein X (HOPX) ( Dmitrieva-Posocco et al, 2022 ). Furthermore, high β-hydroxybutyrate levels decrease nucleotide binding domain and leucine-rich repeat pyrin 3 (NLPR3) inflammasome formation and antagonize proinflammatory cytokine-triggered mitochondrial dysfunction ( Deng et al, 2021 ).…”

Section: Microbial Metabolites Program Mitochondrial Functions With C...mentioning

confidence: 99%

Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer

et al. 2022

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Energy and anabolic metabolism are essential for normal cellular homeostasis but also play an important role in regulating immune responses and cancer development as active immune and cancer cells show an altered metabolic profile. Mitochondria take a prominent position in these metabolic reactions. First, most key energetic reactions take place within or in conjunction with mitochondria. Second, mitochondria react to internal cues from within the cell but also to external cues originating from the microbiota, a vast diversity of associated microorganisms. The impact of the microbiota on host physiology has been largely investigated in the last decade revealing that the microbiota contributes to the extraction of calories from the diet, energy metabolism, maturation of the immune system and cellular differentiation. Thus, changes in the microbiota termed dysbiosis have been associated with disease development including metabolic diseases, inflammation and cancer. Targeting the microbiota to modulate interactions with the mitochondria and cellular metabolism to delay or inhibit disease development and pathogenesis appears an attractive therapeutic approach. Here, we summarize recent advances in developing the therapeutic potential of microbiota-mitochondria interactions for inflammation and cancer.

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β-Hydroxybutyrate suppresses colorectal cancer

Cited by 185 publications

References 40 publications

Dietary regulation in health and disease

Dietary regulation in health and disease

CONNECTOR, fitting and clustering of longitudinal data to reveal a new risk stratification system

Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer

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