Hammouda Zainab Kamel, Wasfi Reham, Abdeltawab Nourtan F
Department of Microbiology and Immunology, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
BMC Microbiol. 2025 Jul 11;25(1):430. doi: 10.1186/s12866-025-04130-0.
It is evident that various drugs influence the gut microbiota, yet the precise mechanism driving these effects remain ambiguous. Considering the growing recognition of gut microbiota's role in health and disease, it is important to explore how commonly used drugs, such as antihistamines, may alter microbial composition and function. Histamine, an essential interkingdom signaling molecule, shapes bacterial virulence, biofilm formation, and immune regulation. However, the effects of antihistamines on bacterial colonization are mostly unknown. This study aimed to investigate the potential effects of antihistamine exposure on critical factors which affect the pathogenicity and colonization of selected gut bacterial species, such as growth, biofilm formation, and adherence to cell lines, at intestinal concentrations. If antihistamines influence bacterial metabolism or composition, they may consequently affect Short Chain Fatty Acid (SCFA) production, which could have downstream effects on gut homeostasis and immune function. Specifically, we examined the impact of three antihistamines - fexofenadine HCl, cyproheptadine HCl, and desloratadine -on bacteria from the four dominant gut phyla: Bifidobacterium longum, Limosilactobacillus reuteri, Bacteroides fragilis, and Escherichia coli.
Our results showed that cyproheptadine HCl and desloratadine inhibited the growth of all tested bacteria, whereas fexofenadine HCl promoted the growth of all species except B. longum. Furthermore, cyproheptadine HCl and desloratadine reduced the biofilm-forming capacity of these bacterial species and altered their effects on adherence to Caco-2/HT-29 cell lines aligning with changes in cell surface hydrophobicity: increased cell surface hydrophobicity correlated with greater bacterial adherence to surfaces. In contrast, fexofenadine HCl enhanced biofilm formation and adherence of B. longum and L. reuterii in Caco-2/HT-29 co-cultures. It also led to increased production of lactic and propionic acids, with a statistically significant increase observed in acetic acid levels (p < 0.05).
In summary, our findings suggest that fexofenadine HCl, unlike cyproheptadine HCl and desloratadine, supports the growth, and colonization of probiotic bacteria such as L. reuteri and B. longum with potential anti allergic benefits, and enhancing their SCFA production. Conversely, cyproheptadine HCl and desloratadine suppressed bacterial growth, hinting at potential antimicrobial properties that may warrant exploration for drug repurposing.
显然，各种药物会影响肠道微生物群，但驱动这些影响的精确机制仍不明确。鉴于对肠道微生物群在健康和疾病中的作用的认识不断增加，探索常用药物（如抗组胺药）如何改变微生物组成和功能非常重要。组胺是一种重要的跨界信号分子，它塑造细菌毒力、生物膜形成和免疫调节。然而，抗组胺药对细菌定植的影响大多未知。本研究旨在调查在肠道浓度下，抗组胺药暴露对影响所选肠道细菌物种致病性和定植的关键因素（如生长、生物膜形成和对细胞系的粘附）的潜在影响。如果抗组胺药影响细菌代谢或组成，它们可能会因此影响短链脂肪酸（SCFA）的产生，这可能会对肠道稳态和免疫功能产生下游影响。具体而言，我们研究了三种抗组胺药——盐酸非索非那定、盐酸赛庚啶和地氯雷他定——对四种主要肠道门类细菌的影响：长双歧杆菌、罗伊氏乳杆菌、脆弱拟杆菌和大肠杆菌。
我们的结果表明，盐酸赛庚啶和地氯雷他定抑制了所有测试细菌的生长，而盐酸非索非那定促进了除长双歧杆菌外所有物种的生长。此外，盐酸赛庚啶和地氯雷他定降低了这些细菌物种的生物膜形成能力，并改变了它们对与细胞表面疏水性变化相关的Caco-2/HT-29细胞系的粘附作用：细胞表面疏水性增加与细菌对表面的更大粘附相关。相比之下，盐酸非索非那定增强了长双歧杆菌和罗伊氏乳杆菌在Caco-2/HT-29共培养物中的生物膜形成和粘附。它还导致乳酸和丙酸产量增加，乙酸水平观察到统计学上的显著增加（p < 0.05）。
总之，我们的研究结果表明，与盐酸赛庚啶和地氯雷他定不同，盐酸非索非那定支持罗伊氏乳杆菌和长双歧杆菌等益生菌的生长和定植，具有潜在的抗过敏益处，并提高它们的SCFA产量。相反，盐酸赛庚啶和地氯雷他定抑制细菌生长，暗示可能具有抗菌特性，值得探索用于药物再利用。
