# Short-term Bacillus clausii administration remodels the peripheral T-cell receptor repertoire through convergent CDR3 sequence architectures

“Short-term Bacillus clausii administration remodels the peripheral T-cell receptor repertoire through convergent CDR3 sequence architectures” (2026), by Angela Mauriello et al. Immunology and Microbiology research paper. Original abstract below, unchanged. A free PDF is available.

- Authors: Angela Mauriello, Ana Mendizabal-Sasieta, Juan Luis Melero, Marta Soto, Marta Grzelak, Mariana Capelli, Holger Heyn, Maria Tagliamonte, Luigi Buonaguro
- Published: November 4, 2026
- Field: Immunology and Microbiology
- DOI: https://doi.org/10.1186/s13027-026-00818-8
- Free PDF: https://www.researchsquare.com/article/rs-10454711/latest.pdf

## Abstract

The intestinal microbiota is a major regulator of systemic immunity, yet its influence on the structural organization of the T-cell receptor (TCR) repertoire remains poorly understood. While probiotic administration has been shown to modulate immune function through changes in cytokine production and immune-cell activity, whether these interventions reshape the architecture of the circulating T-cell repertoire at single-clonotype resolution has not been established. We therefore investigated the longitudinal impact of short-term Bacillus clausii administration on the peripheral TCRβ repertoire using ultra-deep immune repertoire sequencing. Peripheral blood mononuclear cells were collected from a single healthy individual immediately before and after completion of a 10-day oral Bacillus clausii regimen (single-case study). TCRβ repertoires were analyzed using complementary nucleotide- and amino acid-based clonotype definitions. Repertoire richness, diversity, clonal evenness, V(D)J gene usage, repertoire overlap, differential clonotype abundance, CDR3 sequence composition, motif enrichment, and hierarchical sequence clustering were evaluated to characterize quantitative and structural changes induced by probiotic administration. Short-term probiotic administration was associated with marked quantitative remodeling of the peripheral TCRβ repertoire. Repertoire richness and diversity decreased substantially, accompanied by increased clonal focusing and expansion of dominant clonotypes. Despite this contraction of the low-frequency clonotype compartment, the overall structural organization of the repertoire remained remarkably stable. CDR3 length distribution, TRBV/TRBJ gene usage, and dominant V-J rearrangements were largely preserved, while abundance-weighted repertoire similarity remained exceptionally high. Differential abundance analysis demonstrated that repertoire remodeling was driven predominantly by expansion of pre-existing clonotypes rather than widespread emergence of new clones. Moreover, expanded clonotypes segregated into multiple clusters sharing conserved CDR3 sequence motifs despite heterogeneous TRBV and TRBJ usage, revealing recurrent CDR3 amino acid sequence patterns that were independent of germline gene composition. These findings provide preliminary evidence that short-term Bacillus clausii administration may promote selective quantitative remodeling of the peripheral TCRβ repertoire within a largely preserved structural framework. The preferential expansion of pre-existing clonotypes together with the identification of shared CDR3 sequence motifs suggests that microbiota-directed interventions may fine-tune the organization of the adaptive immune repertoire rather than induce wholesale repertoire replacement. Although these findings were observed in a case-single study and require validation in larger controlled cohorts, the ultra-deep immune repertoire sequencing represents a sensitive approach for investigating the systemic immunological effects of microbiota-directed interventions.

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