Olías-Molero Ana Isabel, Botías Pedro, Cuquerella Montserrat, García-Cantalejo Jesús, Barcia Emilia, Torrado Susana, Torrado Juan José, Alunda José María
ICPVet, Department of Animal Health, School of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain.
Genomics Unit, Research Assistance Center of Biological Techniques, Complutense University of Madrid, 28040 Madrid, Spain.
Antibiotics (Basel). 2023 Feb 9;12(2):362. doi: 10.3390/antibiotics12020362.
Visceral leishmaniasis (VL), a vector-borne parasitic disease caused by and (Kinetoplastida), affects humans and dogs, being fatal unless treated. Miltefosine (MIL) is the only oral medication for VL and is considered a first choice drug when resistance to antimonials is present. Comorbidity and comedication are common in many affected patients but the relationship between microbiome composition, drugs administered and their pharmacology is still unknown. To explore the effect of clindamycin on the intestinal microbiome and the availability and distribution of MIL in target organs, Syrian hamsters (120-140 g) were inoculated with (10 promastigotes/animal). Infection was maintained for 16 weeks, and the animals were treated with MIL (7 days, 5 mg/kg/day), clindamycin (1 mg/kg, single dose) + MIL (7 days, 5 mg/kg/day) or kept untreated. Infection was monitored by ELISA and fecal samples (16 wpi, 18 wpi, end point) were analyzed to determine the 16S metagenomic composition (OTUs) of the microbiome. MIL levels were determined by LC-MS/MS in plasma (24 h after the last treatment; end point) and target organs (spleen, liver) (end point). MIL did not significantly affect the composition of intestinal microbiome, but clindamycin provoked a transient albeit significant modification of the relative abundance of 45% of the genera, including , ; and , besides its effect on less abundant phyla and families. Intestinal dysbiosis in the antibiotic-treated animals was associated with significantly lower levels of MIL in plasma, though not in target organs at the end of the experiment. No clear relationship between microbiome composition (OTUs) and pharmacological parameters was found.
内脏利什曼病（VL）是由杜氏利什曼原虫（动质体目）引起的一种媒介传播的寄生虫病，可感染人类和犬类，如不治疗会导致死亡。米替福新（MIL）是唯一用于治疗VL的口服药物，当对锑剂耐药时，它被视为首选药物。合并症和联合用药在许多受影响的患者中很常见，但微生物组组成、所用药物及其药理学之间的关系仍不清楚。为了探究克林霉素对肠道微生物组的影响以及MIL在靶器官中的可用性和分布，给叙利亚仓鼠（120 - 140克）接种杜氏利什曼原虫（每只动物接种10个前鞭毛体）。感染维持16周，然后将动物分为三组进行处理：用MIL治疗（7天，5毫克/千克/天）、克林霉素（1毫克/千克，单次给药）+ MIL（7天，5毫克/千克/天）或不治疗。通过酶联免疫吸附测定（ELISA）监测感染情况，并分析粪便样本（感染后第16周、第18周、实验终点）以确定微生物组的16S宏基因组组成（操作分类单元，OTUs）。通过液相色谱 - 串联质谱法（LC - MS/MS）测定血浆（最后一次治疗后24小时；实验终点）和靶器官（脾脏、肝脏）（实验终点）中的MIL水平。MIL对肠道微生物组的组成没有显著影响，但克林霉素引起了45%的菌属相对丰度的短暂但显著改变，包括双歧杆菌属、真杆菌属、乳杆菌属和阿克曼氏菌属，此外它还对丰度较低的门和科有影响。抗生素治疗组动物的肠道生态失调与血浆中MIL水平显著降低有关，不过在实验结束时靶器官中的MIL水平未受影响。未发现微生物组组成（OTUs）与药理学参数之间存在明确关系。
