Parasite-probiotic interactions in the gut: Bacillus sp. and Enterococcus faecium regulate type-2 inflammatory responses and modify the gut microbiota of pigs during helminth infection

Dietary probiotics have been shown to enhance gut health by directly competing with pathogenic agents and through immunostimulatory effects. These properties are recognized in the context of bacterial and viral pathogens, but less is known about interactions with eukaryotic pathogens such as parasitic worms. We investigated whether two probiotic mixtures comprised of Bacillus amyloliquefaciens, B. subtilis, and Enterococcus faecium, or Lactobacillus rhamnosus LGG and Bifidobacterium animalis subspecies Lactis Bb12, could modulate helminth infection kinetics as well as the gut microbiome and intestinal immune responses in pigs infected with the porcine nodular worm, Oesophagostomum dentatum. We observed that neither probiotic mixture influenced helminth infection levels. BBE, and to a lesser extent LB, changed the alpha- and beta-diversity indices of the colon and faecal microbiota, including enrichment of faecal Bifidobacterium spp. by BBE. However, these effects were muted by concurrent O. dentatum infection. BBE significantly attenuated the O. dentatum-induced upregulation of genes involved in type2 inflammation and restored normal lymphocyte ratios in the ileocaecal lymph nodes that were altered by infection. Moreover, inflammatory cytokine release from blood mononuclear cells and intestinal lymphocytes were diminished by BBE. Collectively, our data suggest that selected probiotic mixtures can play a role in maintaining immune homeostasis during Th2biased inflammation. In addition, potentially beneficial changes in the microbiome induced by dietary probiotics may be counteracted by helminths, highlighting the complex inter-relationships that potentially exist between probiotic bacteria and intestinal parasites.

已有研究证实，膳食益生菌可通过直接竞争病原微生物以及发挥免疫刺激效应来改善肠道健康。这类功能在针对细菌和病毒病原体的研究中已得到充分验证，但对于益生菌与寄生蠕虫等真核病原体的互作机制，目前仍有待深入探究。本研究旨在评估两种益生菌混合物——分别由解淀粉芽孢杆菌（Bacillus amyloliquefaciens）、枯草芽孢杆菌（Bacillus subtilis）与粪肠球菌（Enterococcus faecium）组成，以及由鼠李糖乳杆菌LGG（Lactobacillus rhamnosus LGG）和动物双歧杆菌乳亚种Bb12（Bifidobacterium animalis subsp. Lactis Bb12）组成——对感染猪结节虫（齿口线虫，Oesophagostomum dentatum）的仔猪的蠕虫感染动力学、肠道微生物组以及肠道免疫应答的调节作用。实验结果显示，两种益生菌混合物均未对仔猪的蠕虫感染负荷产生显著影响。其中，BBE可显著改变结肠与粪便微生物群的α多样性和β多样性指数，其中包括BBE介导的粪便双歧杆菌属（Bifidobacterium spp.）富集效应；而LB的该类效应相对较弱。不过，当仔猪同时感染齿口线虫时，上述微生物组调控效应均被显著削弱。BBE可显著抑制齿口线虫感染诱导的2型炎症相关基因的上调，并可恢复感染所致的回盲淋巴结淋巴细胞比例异常。此外，BBE还可降低外周血单个核细胞与肠道淋巴细胞的炎性细胞因子释放量。综上，本研究数据表明，特定的益生菌混合物可在Th2偏态炎症过程中维持免疫稳态。此外，膳食益生菌诱导的微生物组潜在有益变化可能会被寄生蠕虫抵消，这凸显了益生菌与肠道寄生虫之间可能存在的复杂相互关系。