Pushkarna Samridhi, Kumar Anil, Arora Kiran, Malhotra Parveen, Suneja Pooja, Dang Amita Suneja
Centre for Medical Biotechnology, Maharshi Dayanand University, Rohtak, 124001, Haryana, India.
Kirori Mal College, University of Delhi, Delhi, 10007, India.
Ir J Med Sci. 2025 Aug 13. doi: 10.1007/s11845-025-04044-w.
Celiac disease (CeD), a multifactorial disorder, develops when gluten, the toxic environmental inducer, interacts with CeD susceptibility genetic markers, resulting in a chronic enteropathy. Several extra-intestinal complications may also arise in cases of delayed management. There persists a growing demand to develop non-dietary adjuvant therapeutic options that can help relieve symptoms and improve patients' quality of life.
The present study conducted a bioinformatic approach to look into the potential of using Lactobacillus rhamnosus, a well-established probiotic, as gluten-digesting bacteria and provide the basis for future therapeutic developments.
Complete genome assemblies of forty-nine L. rhamnosus strains were subjected to annotation using RAST and a pan genome analysis with BPGA. Genes for peptidases were identified using BlastKOALA and Prokka, followed by domain analysis using the NCBI-CD search tool to screen for gluten-digesting activity.
Genome annotation of all the strains under study highlighted the presence of sixty-one peptidases in L. rhamnosus. Domain analysis further revealed that nine of these peptidases, including aminopeptidase N, neutral endopeptidase, oligoendopeptidase F, dipeptidyl-peptidase 5, proline iminopeptidase, Xaa-Pro dipeptidyl-peptidase, aminopeptidase C, aminopeptidase E, and PII-type proteinase, shared domains with already established gluten-digesting enzymes, suggesting their potential role in degrading toxic gliadin peptides.
The current in silico analysis indicates that this well-known probiotic species, in addition to showcasing a plethora of beneficial properties, may also hold great potential in terms of reducing gluten toxicity. With further studies, L. rhamnosus can prove to be a promising candidate in CeD treatment and management.
乳糜泻（CeD）是一种多因素疾病，当有毒的环境诱导物麸质与CeD易感基因标记相互作用时就会发病，导致慢性肠病。如果治疗延迟，还可能出现几种肠外并发症。开发非饮食辅助治疗方案的需求持续增长，这些方案有助于缓解症状并提高患者的生活质量。
本研究采用生物信息学方法，探讨将成熟的益生菌鼠李糖乳杆菌用作消化麸质的细菌的潜力，并为未来的治疗发展提供依据。
对49株鼠李糖乳杆菌菌株的完整基因组组装体进行RAST注释，并使用BPGA进行泛基因组分析。使用BlastKOALA和Prokka鉴定肽酶基因，随后使用NCBI-CD搜索工具进行结构域分析，以筛选消化麸质的活性。
对所有研究菌株的基因组注释突出显示，鼠李糖乳杆菌中存在61种肽酶。结构域分析进一步表明，这些肽酶中的9种，包括氨肽酶N、中性内肽酶、寡肽酶F、二肽基肽酶5、脯氨酸亚氨基肽酶、Xaa-Pro二肽基肽酶、氨肽酶C、氨肽酶E和PII型蛋白酶，与已确定的消化麸质的酶具有共同结构域，表明它们在降解有毒麦醇溶蛋白肽方面的潜在作用。
目前的计算机分析表明，这种著名的益生菌物种除了具有大量有益特性外，在降低麸质毒性方面也可能具有巨大潜力。通过进一步研究，鼠李糖乳杆菌可能被证明是CeD治疗和管理中有前景的候选者。
