Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation

Shi, Bozhong; Li, Haoyu; He, Xiaomin

doi:10.1080/19490976.2024.2323237

Cited by 5 publications

(1 citation statement)

References 226 publications

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“…Moreover, the dramatic inter-individual variation in GM composition and host dietary habit poses significant difficulties for GM and altered metabolites converting into AF prevention and treatment targets. Individual precision treatment regiments based on machine learning datasets, including diet, GM, and genetics, as well as artificial intelligence (AI) techniques might help address this challenge [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels

Fang,

Zuo,

Liu

et al. 2024

Eur J Med Res

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Background Atrial fibrillation (AF) is associated with circulating inflammation. Short-chain fatty acids (SCFAs) derived from gut microbiota (GM) regulate leukocyte function and inhibit the release of inflammatory cytokines, which are partly mediated by the G-protein-coupled receptor 43 (GPR43) signaling. This study aimed to investigate the expression of GPR43/NOD-like receptors family pyrin domain containing 3 (NLRP3) in leukocytes and the interaction with intestinal SCFAs levels in AF patients. Methods Expressions of GPR43 and NLRP3 mRNA in peripheral blood leukocytes from 23 AF patients and 25 non-AF controls were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Expressions of leukocyte GPR43 and NLRP3 protein were evaluated by western blot analysis. The levels of plasma IL-1β were measured by enzyme-linked immunosorbent assay (ELISA). The fecal SCFAs levels based on GC/MS metabolome of corresponding 21 controls and 14 AF patients were acquired from our published dataset. To evaluate the expression of NLRP3 and GPR43 and the release of IL-1β, human THP-1 cells were stimulated with or without SCFAs (acetate, propionate, and butyrate), lipopolysaccharide (LPS), and nigericin in vitro, respectively. Results Compared to the controls, the mRNA expression in peripheral leukocytes was significantly reduced in AF patients (P = 0.011) coupled with the increase in downstream leukocyte NLRP3 mRNA expression (P = 0.007) and plasma IL-1β levels (P < 0.001), consistent with changes in GPR43 and NLRP3 protein expression. Furthermore, leukocyte GPR43 mRNA levels were positively correlated with fecal GM-derived acetic acid (P = 0.046) and negatively correlated with NLRP3 mRNA expression (P = 0.024). In contrast to the negative correlation between left atrial diameter (LAD) and GPR43 (P = 0.008), LAD was positively correlated with the leukocyte NLRP3 mRNA levels (P = 0.024). Subsequent mediation analysis showed that 68.88% of the total effect of intestinal acetic acid on AF might be mediated by leukocyte GPR43/NLRP3. The constructed GPR43–NLRP3 score might have a predictive potential for AF detection (AUC = 0.81, P < 0.001). Moreover, SCFAs treatment increased GPR43 expression and remarkably reduced LPS/nigericin-induced NLRP3 expression and IL-1β release in human THP-1 cells in vitro. Conclusions Disrupted interactions between GPR43 and NLRP3 expression in peripheral blood leukocytes, associated with reduced intestinal GM-derived SCFAs, especially acetic acid, may be involved in AF development and left atrial enlargement by enhancing circulating inflammation.

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Section: Discussionmentioning

confidence: 99%

Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels

Fang,

Zuo,

Liu

et al. 2024

Eur J Med Res

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The role and mechanism of gut-lung axis mediated bidirectional communication in the occurrence and development of chronic obstructive pulmonary disease

Song,

Dou,

Chang

et al. 2024

Gut Microbes

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Human and gut microbiota synergy in a metabolically active superorganism: a cardiovascular perspective

Russo,

Puccetti,

Costantini

et al. 2024

Front. Cardiovasc. Med.

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Despite significant advances in diagnosis and treatment over recent decades, cardiovascular disease (CVD) remains one of the leading causes of morbidity and mortality in Western countries. This persistent burden is partly due to the incomplete understanding of fundamental pathogenic mechanisms, which limits the effectiveness of current therapeutic interventions. In this context, recent evidence highlights the pivotal role of immuno-inflammatory activation by the gut microbiome in influencing cardiovascular disorders, potentially opening new therapeutic avenues. Indeed, while atherosclerosis has been established as a chronic inflammatory disease of the arterial wall, accumulating data suggest that immune system regulation and anti-inflammatory pathways mediated by gut microbiota metabolites play a crucial role in a range of CVDs, including heart failure, pericardial disease, arrhythmias, and cardiomyopathies. Of particular interest is the emerging understanding of how tryptophan metabolism—by both host and microbiota—converges on the Aryl hydrocarbon Receptor (AhR), a key regulator of immune homeostasis. This review seeks to enhance our understanding of the role of the immune system and inflammation in CVD, with a focus on how gut microbiome-derived tryptophan metabolites, such as indoles and their derivatives, contribute to cardioimmunopathology. By exploring these mechanisms, we aim to facilitate the development of novel, microbiome-centered strategies for combating CVD.

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Advancing lifelong precision medicine for cardiovascular diseases through gut microbiota modulation

Cited by 5 publications

References 226 publications

Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels

Disordered GPR43/NLRP3 expression in peripheral leukocytes of patients with atrial fibrillation is associated with intestinal short chain fatty acids levels

The role and mechanism of gut-lung axis mediated bidirectional communication in the occurrence and development of chronic obstructive pulmonary disease

Human and gut microbiota synergy in a metabolically active superorganism: a cardiovascular perspective

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