Short chain fatty acids released by Fusobacterium nucleatum are neutrophil chemoattractants acting via free fatty acid receptor 2 (FFAR2),Cellular Microbiology

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Short chain fatty acids released by Fusobacterium nucleatum are neutrophil chemoattractants acting via free fatty acid receptor 2 (FFAR2)
Cellular Microbiology ( IF 2.6 ) Pub Date : 2021-04-29 , DOI: 10.1111/cmi.13348
Agnes Dahlstrand Rudin ₁ , Arsham Khamzeh ₁ , Vignesh Venkatakrishnan ₂ , Amina Basic ₁ , Karin Christenson ₁ , Johan Bylund ₁

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Fusobacterium nucleatum is a gram-negative and anaerobic oral commensal that is implicated in inflammatory conditions of the tooth-supporting structures, that is, periodontal diseases. One of the main characteristics of these conditions is an accumulation of neutrophil granulocytes in the gingival pockets where bacteria reside. Neutrophils are recruited to tissue-residing microbes by gradients of bacteria derived chemoattractants, and the cellular migration over the pocket epithelium into the gingival pocket is likely governed by chemoattractants released by the amino acid fermenting anaerobes typically colonising this site. However, the chemoattractants released by F. nucleatum and other oral anaerobes have long been unidentified. In the present study, we show that the major chemoattractants released during the growth of F. nucleatum are short chain fatty acids (SCFAs), primarily acetate and butyrate. These SCFAs, that are released at high levels as end-products of the metabolism of F. nucleatum, trigger chemotaxis of human neutrophils, as well as cytosolic Ca²⁺ signals, via free fatty acid receptor 2 (FFAR2). This finding establishes the SCFA-FFAR2 interaction as an important mechanism in the recruitment of neutrophils to the periodontal pocket, but could also be of importance in the pathogenesis of other medical conditions involving colonisation/infection of F. nucleatum.

中文翻译：

具核梭杆菌释放的短链脂肪酸是通过游离脂肪酸受体 2 (FFAR2) 发挥作用的中性粒细胞趋化剂

具核梭杆菌是一种革兰氏阴性和厌氧的口腔共生菌，与牙齿支撑结构的炎症状况有关，即牙周病。这些病症的主要特征之一是嗜中性粒细胞在细菌所在的牙龈袋中积累。中性粒细胞通过细菌衍生的化学引诱剂的梯度被招募到组织驻留微生物中，并且细胞通过袋上皮细胞迁移到牙龈袋中可能受通常在该位点定殖的氨基酸发酵厌氧菌释放的化学引诱剂的控制。然而，F. nucleatum释放的化学引诱剂和其他口腔厌氧菌早已不为人知。在本研究中，我们表明在F. nucleatum生长过程中释放的主要化学引诱物是短链脂肪酸 (SCFA)，主要是乙酸盐和丁酸盐。这些 SCFA 作为具核梭菌代谢的终产物以高水平释放，通过游离脂肪酸受体 2 (FFAR2)触发人类中性粒细胞的趋化性以及胞质 Ca ^2+信号。这一发现确立了 SCFA- FFAR2相互作用是中性粒细胞向牙周袋募集的重要机制，但在涉及具核梭菌定植/感染的其他医学疾病的发病机制中也可能具有重要意义。

更新日期：2021-04-29

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