The gut microbiome is now widely regarded as a key organ of the immune system rather than a passive passenger in the intestine. Over the past decade, mechanistic and clinical studies have shown that microbial communities shape both innate and adaptive immunity, influencing susceptibility to infection, inflammatory disease and even responses to vaccines and cancer immunotherapy. Reviews of the field consistently highlight a bidirectional dialogue: immune cells educate the microbiota, while microbial metabolites and surface structures continuously tune host immunity across the life course. [1]

At birth, contact with maternal and environmental microbes initiates a rapid colonisation of the neonatal gut. This early community, enriched in obligate anaerobes such as bifidobacteria, interacts with pattern-recognition receptors on epithelial and immune cells (for example Toll-like receptors and NOD-like receptors), promoting the maturation of gut-associated lymphoid tissue and the establishment of oral tolerance. When this process is perturbed, for instance by caesarean delivery or antibiotics, experimental and human data suggest an increased risk of allergy, autoimmunity and infection later in life. [1]

Microbial metabolites as key mediators of gut–immune communication

Microbial metabolites are central to this immune dialogue. Short-chain fatty acids (SCFAs) such as acetate, propionate and butyrate, produced by the fermentation of dietary fibres, act as signalling molecules that influence T-cell differentiation, B-cell antibody production and epithelial barrier integrity. Butyrate, in particular, promotes the differentiation of colonic Foxp3⁺ regulatory T cells via histone deacetylase inhibition and G-protein-coupled receptor signalling, thereby dampening excessive inflammation and protecting from colitis in preclinical models. [2] More recent work confirms that SCFAs can drive both effector and regulatory responses, with the net effect depending on tissue context and inflammatory tone, and that SCFA-mediated imprinting of T cells is a promising therapeutic lever in immune-mediated disease. [3]

When the composition or function of the gut microbiome is disturbed, so-called dysbiosis, the result can be a breakdown of immune homeostasis. Inflammatory bowel disease (IBD), for example, is characterised by reduced microbial diversity, depletion of SCFA-producing taxa and expansion of pathobionts, all of which correlate with impaired barrier function and exaggerated mucosal immune responses. [4] Similar patterns are increasingly described in systemic conditions such as rheumatoid arthritis (RA), where specific microbial signatures and metabolite profiles associate with autoantibody formation and disease activity, suggesting that gut dysbiosis may contribute causally to the loss of tolerance. [5] More broadly, the gut microbiota is now viewed as a druggable target in immune tolerance and autoimmunity, with strategies ranging from diet and prebiotics to defined consortia of “immunobiotics”. [6]

Within this conceptual framework, strain-selected probiotics, particularly bifidobacteria and lactobacilli sensu lato, are being evaluated as tools to reinforce mucosal defences and re-establish balanced immune responses. Preclinical models show that certain Bifidobacterium breve strains can attenuate allergic inflammation by enhancing regulatory T-cell activity and skewing T-helper responses away from Th2 dominance, while also modulating gut microbiota composition.  [7] Other B. breve strains improve immune function in immunosuppressed animals, for example by restoring splenic and intestinal cytokine profiles and reducing oxidative stress. [8] In parallel, clinical and translational data for Lactobacillus/Lacticaseibacillus and related species indicate that specific strains can enhance vaccine responses, support upper respiratory tract defences and reduce the incidence or duration of respiratory infections, especially in children. [9]

Coree infant-derived probiotic strains as tools to reinforce mucosal immunity

Three infant-derived strains, Bifidobacterium breve 2TA LMG P-30999, Lactobacillus gasseri L6 LMG P-30998 and Lacticaseibacillus rhamnosus (formerly Lactobacillus rhamnosus) L13b LMG P-31000, isolated and developed by Coree srl are potentially interesting for immune support. These strains have been genomically characterised for safety (absence of acquired antibiotic-resistance and virulence genes) and equipped with traits relevant for gut survival, such as acid and bile tolerance and adhesion factors, supporting their use as next-generation probiotics. 

B. breve LMG P-30999, isolated from infant faeces, combines classical bifidobacterial features, such as the ability to utilise human milk oligosaccharides and synthesise B-group vitamins, with a strong immunomodulatory profile. In the Coree in-vitro platform, this strain induces IL-10 release from human peripheral blood mononuclear cells, consistent with a tolerogenic, anti-inflammatory imprinting of host immunity, and contributes to down-regulation of pro-inflammatory cytokines (TNF-α, IL-8) in inflamed intestinal epithelial cells, particularly in a preventive (pre-treatment) setting. [10] These observations mirror the broader literature in which B. breve strains alleviate experimental allergic rhinitis and food allergy by expanding CD4⁺CD25⁺Foxp3⁺ regulatory T cells and normalising Th1/Th2 balance, as well as improving immune status in chemically immunosuppressed mice. [7] From a translational perspective, LMG P-30999 thus appears particularly attractive for early-life formulations aimed at supporting physiological immune maturation and promoting tolerance in at-risk populations, pending dedicated clinical trials.

L. gasseri LMG P-30998, also infant-derived, carries genes for acid and bile resistance and encodes bacteriocin production, suggesting a capacity to both persist in the gut and inhibit competing pathobionts. In Coree’s human cell models, viable and heat-inactivated preparations of this strain stimulate IL-10 and, notably, IL-12p70 in peripheral blood mononuclear cells, a cytokine profile compatible with balanced activation of innate and Th1-type responses without excessive inflammation. [10] This fact fits well with data from other L. gasseri / L. paragasseri strains, where oral intake has been shown to increase mucosal secretory IgA, enhance influenza vaccine-specific antibody responses, and reduce common cold symptoms while modulating NK-cell and innate immune markers in healthy adults. [9] Combined with the dossier’s demonstration of antioxidant properties and capacity to attenuate cytokine responses in inflammatory models, LMG P-30998 emerges as a promising candidate to reinforce mucosal barrier and humoral defences in the upper and lower airways as well as in the gut, potentially also in heat-inactivated (postbiotic) formats. 

Lacticaseibacillus rhamnosus LMG P-31000 stands out for a particularly broad range of immune-relevant activities. In Coree’s in-vitro systems, this strain induces IL-10 in human immune cells, mitigates IL-6 and IL-8 up-regulation in epithelial models exposed to chemical or pathogen-induced inflammation, and displays anti-biofilm activity against key respiratory and skin pathogens when used as a postbiotic. It also counteracts oxidative stress in Caco-2 cells and helps maintain tight-junction gene expression after hydrogen peroxide exposure, pointing to a role in preserving barrier integrity under inflammatory conditions. Remarkably, LMG P-31000 reduces PD-L1 expression in colorectal cancer cell lines and shows additive effects with a PD-L1 inhibitor, suggesting a potential adjuvant role in checkpoint blockade therapy, though this remains entirely preclinical at present. [10]

These properties are highly consistent with the extensive literature on L. rhamnosus GG (LGG) and related strains. Randomised controlled trials and meta-analyses have reported reductions in upper respiratory tract infections, acute otitis media and antibiotic use in children receiving LGG, as well as shorter duration of respiratory symptoms in specific subgroups. [11] Although strain-specificity is crucial and the Coree LMG P-31000 strain requires its own clinical documentation, its in-vitro signature—combining immunomodulation, barrier protection and anti-biofilm activity—aligns with the immunobiotic profile that has made L. rhamnosus species a cornerstone of probiotic research.

From microbiome–immune crosstalk to strain-level interventions and future perspectives

Taken together, the available evidence underscores a continuum from ecosystem-level microbiome–immune crosstalk to strain-level interventions. A healthy, fibre-fed gut microbiome provides a metabolite environment that supports regulatory T-cell differentiation, robust barrier function and effective, but not excessive, immune responses. [2] Within this framework, strains such as B. breve LMG P-30999, L. gasseri LMG P-30998 and L. rhamnosus LMG P-31000 represent rationally selected tools to reinforce specific facets of mucosal immunity, tolerance, humoral protection and barrier integrity, while also offering postbiotic applications where the use of viable bacteria is not desirable. The next step will be to translate their promising preclinical profiles into well-designed human trials that define indications, target populations and clinically meaningful immune outcomes.

References

PubMed-indexed sources, in order of citation

  1. Yoo JY, Groer M, Dutra SVO, Sarkar A, McSkimming DI. Gut microbiota and immune system interactions. Microorganisms. 2020;8(10):1587. PMID: 33076307. 
  2. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446–450. PMID: 24226770. 
  3. Saadh MJ, Aldossary AM, Al-Harthi J, et al. The effects of microbiota-derived short-chain fatty acids on T-cell function. Semin Immunol. 2025;69:101812. PMID: 40136436.
  4. Bretto E, Urpì-Ferreruela M, Casanova GR, González-Suárez B. The Role of Gut Microbiota in Gastrointestinal Immune Homeostasis and Inflammation: Implications for Inflammatory Bowel Disease. Biomedicines. 2025 Jul 24;13(8):1807. doi: 10.3390/biomedicines13081807. PMID: 40868062; PMCID: PMC12383986.
  5. Qi P, Chen X, Tian J, Zhong K, Qi Z, Li M, Xie X. The gut homeostasis-immune system axis: novel insights into rheumatoid arthritis pathogenesis and treatment. Front Immunol. 2024 Sep 26;15:1482214. doi: 10.3389/fimmu.2024.1482214. PMID: 39391302; PMCID: PMC11464316.
  6. Almansour N, Howell N, Candon S. Gut microbiota: a promising new target in immune tolerance. Curr Opin Immunol. 2025;87:102349. PMID: 40084744.
  7. Ren J, Liu T, Liu X, et al. Effects of Bifidobacterium breve feeding strategy and delivery modes on allergic rhinitis in mice. PLoS One. 2015;10(10):e0140018. PMID: 26439865.
  8. Fang H, Chen X, Lu W, et al. Bifidobacterium breve CCFM1310 enhances immunity in cyclophosphamide-induced immunosuppressed mice. J Funct Foods. 2024;115:105071. PMID: 38747771.
  9. Nishihira J, Kagami-Katsuyama H, Tanaka A, et al. Lactobacillus gasseri SBT2055 stimulates immunoglobulin production and innate immunity after influenza vaccination: a randomized double-blind, placebo-controlled trial. Funct Foods Health Dis. 2016;6(9):544–568. PMID: 28491071.
  10. Internal data, available upon request
  11. Hojsak I, Snovak N, Abdović S, et al. Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children attending day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2010;29(3):312–316. PMID: 19896252.