Applications and Mechanism of 3‐Hydroxybutyrate (3HB) for Prevention of Colonic Inflammation and Carcinogenesis as a Food Supplement

Li, Zihua; Zhang, Shujie; Zhang, Yudian; Chen, Jin; Wu, Fuqing; Liu, Gang; Chen, Guoqiang

doi:10.1002/mnfr.202100533

Cited by 14 publications

(6 citation statements)

References 51 publications

(54 reference statements)

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“…Palmitic acid, a saturated fatty acid, has been more consistently associated with CRC pathogenesis in scientific literature than linoleic acid, an unsaturated fatty acid, which shows mixed results in terms of CRC correlation [62][63][64]. 3-hydroxybutyrate, a ketone body and product of fatty acid degradation, was also upregulated in CRC (Table 3), but also shows an unclear relationship with CRC, and it was indicated to drive cancer proliferation in some studies while to be better prognostic outcomes when upregulated in other studies [65,66]. Lysophosphatidylcholines of varying lengths were downregulated in CRC patients, while free choline was also found to be downregulated (Table 3).…”

Section: Frequently Reported Metabolite Biomarkers In Crc Studiesmentioning

confidence: 99%

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

Gold

Choueiry

Jin

et al. 2022

Cancers

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Colorectal cancer (CRC) is a highly prevalent disease with poor prognostic outcomes if not diagnosed in early stages. Current diagnosis techniques are either highly invasive or lack sufficient sensitivity. Thus, identifying diagnostic biomarkers of CRC with high sensitivity and specificity is desirable. Metabolomics represents an analytical profiling technique with great promise in identifying such biomarkers and typically represents a close tie with the phenotype of a specific disease. We thus conducted a systematic review of studies reported from January 2012 to July 2021 relating to the detection of CRC biomarkers through metabolomics to provide a collection of knowledge for future diagnostic development. We identified thirty-seven metabolomics studies characterizing CRC, many of which provided metabolites/metabolic profile-based diagnostic models with high sensitivity and specificity. These studies demonstrated that a great number of metabolites can be differentially regulated in CRC patients compared to healthy controls, adenomatous polyps, or across stages of CRC. Among these metabolite biomarkers, especially dysregulated were certain amino acids, fatty acids, and lysophosphatidylcholines. Additionally, we discussed the contribution of the gut bacterial population to pathogenesis of CRC through their modulation to fecal metabolite pools and summarized the established links in the literature between certain microbial genera and altered metabolite levels in CRC patients. Taken together, we conclude that metabolomics presents itself as a promising and effective method of CRC biomarker detection.

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Section: Frequently Reported Metabolite Biomarkers In Crc Studiesmentioning

confidence: 99%

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

Gold

Choueiry

Jin

et al. 2022

Cancers

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“…3HB can significantly reduce the levels of liver damage markers ALT, AST, and TBIL, alleviate CCl 4 -induced liver injury, and protect normal liver function. Previous studies have shown that 3HB has anti-inflammatory effects in animal models of colonic inflammation, atherosclerosis, alcoholic liver injury and depression [17,[25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Ketone body 3-hydroxybutyrate alleviates CCl4-induced liver fibrosis in mice through regulation of mitochondrial fission and reduction of oxidative stress

Zhang,

Liu,

Wang

et al. 2024

Preprint

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3-Hydroxybutyrate (3HB) is an important metabolite and regulatory molecule produced in liver. Previous studies have shown that 3HB could be beneficial to many diseases, including brain diseases, diabetes, and most importantly, inflammation and liver related injury. Therefore, the effect of 3HB on liver fibrosis, one key step of liver diseases which proved to be reversible, is urgent to explore. In this study, the CCl4-induced mouse model of liver fibrosis has been successfully constructed and treated by 3HB. The results demonstrate that 3HB could alleviate CCl4-induced liver injury and inflammation in mice, decrease the accumulation of collagen, the expression of pro-fibrotic genes as well as inflammatory factors, and finally the degree of liver fibrosis. The transcriptome data recovers that the anti-fibrotic effect of 3HB might be exerted through several ways, such as reducing oxidative stress, improving mitochondrial function and p53 signaling pathways, proposing a safe and relatively fast possibility for the treatment of liver fibrosis.

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“…Previous study 12 and our results show that the expression of IL6 is correlated with the severity of radiation-induced damage and therefore is a good marker of RP. Although 3HB has been shown to have significant therapeutic effects in colitis and colorectal cancer, 31,32 it remains unknown whether 3HB serves as an immune effector. We confirmed that 3HB directly downregulates radiation-induced IL6 expression and exerts a radioprotective effect.…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota-derived 3-hydroxybutyrate blocks GPR43-mediated IL6 signaling to ameliorate radiation proctopathy

Chen

et al. 2023

Preprint

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Radiation proctopathy (RP) is a common complication of pelvic radiotherapy but lacking effective treatment. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, we reveal that the fecal and serous concentrations of microbiota-derived 3-hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6-mediated radiation damage. Such a radioprotection of 3HB is mediated by GPR43. Akkermansia muciniphila, with a significant reduction in RP mice and patients, is associated with lower 3HB concentration. Treatment of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage in mice. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block the GPR43-mediated IL6 signaling, thereby conferring radioprotection in RP mice. Our findings reveal a novel implication of the gut-immune axis in radiation pathophysiology, with potential therapeutic applications.

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Applications and Mechanism of 3‐Hydroxybutyrate (3HB) for Prevention of Colonic Inflammation and Carcinogenesis as a Food Supplement

Cited by 14 publications

References 51 publications

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

The Application of Metabolomics in Recent Colorectal Cancer Studies: A State-of-the-Art Review

Ketone body 3-hydroxybutyrate alleviates CCl4-induced liver fibrosis in mice through regulation of mitochondrial fission and reduction of oxidative stress

Gut Microbiota-derived 3-hydroxybutyrate blocks GPR43-mediated IL6 signaling to ameliorate radiation proctopathy

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