Can Lacticaseibacillus rhamnosus CRL1505 postbiotic improve emergency myelopoiesis in immunocompromised mice?

We evaluated whether viable and non-viable Lacticaseibacillus rhamnosus CRL1505 (Lr05V or Lr05NV, respectively) was able to improve emergency myelopoiesis induced by Streptococcus pneumoniae (Sp) infection. Adult Swiss-mice were orally treated with Lr05V or Lr05NV during five consecutive days. The Lr05V and Lr05NV groups and untreated control group received an intraperitoneal dose of cyclophosphamide (Cy-150 mg/kg). Then, the mice were nasally challenged with Sp (107 UFC/mice) on day 3 post-Cy injection. After the pneumococcal challenge, the innate and myelopoietic responses were evaluated. The control group showed a high susceptibility to pneumococcal infection, an impaired innate immune response and a decrease of hematopoietic stem cells (HSCs: Lin-Sca-1+c-Kit+), and myeloid multipotent precursors (MMPs: Gr-1+Ly6G+Ly6C-) in bone marrow (BM). However, lactobacilli treatments were able to significantly increase blood neutrophils and peroxidase-positive cells, while improving cytokine production and phagocytic activity of alveolar macrophages. This, in turn, led to an early Sp lung clearance compared to the control group. Furthermore, Lr05V was more effective than Lr05NV to increase growth factors in BM, which allowed an early HSCs and MMPs recovery with respect to the control group. Both Lr05V and Lr05NV were able to improve BM emergency myelopiesis and protection against respiratory pathogens in mice undergoing chemotherapy.

Topical Administration of Lactiplantibacillus plantarum Accelerates the Healing of Chronic Diabetic Foot Ulcers through Modifications of Infection, Angiogenesis, Macrophage Phenotype and Neutrophil Response.

This work aimed to evaluate the adjuvant treatment to surgical debridement using topical applications of Lactiplantibacillus plantarum ATCC 10241 cultures in complicated diabetic foot ulcers as compared to diabetic foot ulcers receiving surgical wound debridement. A randomised controlled trial was performed involving 22 outpatients with complicated diabetic foot ulcers that either received surgical debridement (SuDe, n = 12) or surgical debridement plus topical applications of L. plantarum cultures (SuDe + Lp, n = 10) every week during a 12 week treatment period. Compared to patients receiving SuDe, patients treated with SuDe + Lp exhibited significantly increased fibroplasia and angiogenesis, as determined by Masson's trichrome staining and the study of CD34 cells, α-smooth muscle actin to semi-quantify vascular area, number of vessels and endothelial cells. In addition, a promotion of the polarisation of macrophages from M1 (CD68) to M2 (CD163) phenotype was observed in SuDe + Lp patients with remarkable differences in the tissue localisation. Bacterial counts were significantly diminished in the SuDe + Lp group compared to the SuDe group. Ex vivo assays, using polymorphonuclears isolated from peripheral blood of patients with diabetes and healthy individuals and challenged with Staphylococcus aureus demonstrated that the addition of L. plantarum supernatants significantly improved the phagocytosis of these cells. L. plantarum-secreted components increased the neutrophils bactericidal activity and regulated the netosis induced by S. aureus. At day 49, the average wound area reduction with SuDe + Lp was 73.5% compared with 45.8% for SuDe (p < 0.05). More patients progressed to closure with SuDe + Lp compared with SuDe treatment, indicating the ability of L. plantarum to accelerate the healing. At day 60, 60% of patients treated with SuDe + Lp achieved 100% of wound area reduction compared with 40% for SuDe. We propose that SuDe + Lp could be an effective adjuvant to surgical debridement when SuDe is not satisfactory for patients with complicated diabetic foot ulcers. The treatment is cheap and easy to apply and the product is easy to obtain.

The Role of Immunobiotics and Postbiotics in the Recovery of Immune Cell Populations From Respiratory Mucosa of Malnourished Hosts: Effect on the Resistance Against Respiratory Infections.

Malnutrition is associated with a state of secondary immunodeficiency, which is characterized by a worsening of the immune response against infectious agents. Despite important advances in vaccines and antibiotic therapies, the respiratory infections are among the leading causes of increased morbidity and mortality, especially in immunosuppressed hosts. In this review, we examine the interactions between immunobiotics-postbiotics and the immune cell populations of the respiratory mucosa. In addition, we discuss how this cross talk affects the maintenance of a normal generation of immune cells, that is crucial for the establishment of protective innate and adaptive immune responses. Particular attention will be given to the alterations in the development of phagocytic cells, T and B lymphocytes in bone marrow, spleen and thymus in immunosuppression state by protein deprivation. Furthermore, we describe our research that demonstrated that the effectiveness of immunobiotics nasal administration in accelerating the recovery of the respiratory immune response in malnourished hosts. Finally, we propose the peptidoglycan from the immunobiotic Lactobacillus rhamnosus CRL1505 as the key cellular component for the effects on mucosal immunity, which are unique and cannot be extrapolated to other L. rhamnosus or probiotic strains. In this way, we provide the scientific bases for its application as a mucosal adjuvant in health plans, mainly aimed to improve the immune response of immunocompromised hosts. The search for safe vaccine adjuvants that increase their effectiveness at the mucosal level is a problem of great scientific relevance today.

Are the immunomodulatory properties of Lactobacillus rhamnosus CRL1505 peptidoglycan common for all Lactobacilli during respiratory infection in malnourished mice?

Previously, we reported that Lactobacillus rhamnosus CRL1505 peptidoglycan (PG05) improves the innate immune response in immunocompromised-malnourished mice after Streptococcus pneumoniae infection. This study extends those previous findings by demonstrating that the dietary recovery of malnourished mice with nasal administration of PG05 improves not only the innate immune response but the respiratory and systemic adaptive humoral response as well. PG05 enhanced the Th2 response, the recovery of B cells, and the concentration and opsonophagocytic activity of anti-pneumococcal antibodies. In addition, by performing comparative studies with the peptidoglycans from lactobacilli of the same species (L. rhamnosus CRL534) or with similar immunomodulatory properties (L. plantarum CRL1506), we demonstrated here that PG05 has unique immunomodulatory properties that cannot be extended to peptidoglycans from other probiotic strains. However, the knowledge of the molecular characteristics of PG05 is indispensable to understand immunomodulatory abilities of L. rhamnosus CRL1505.

Non-viable immunobiotic Lactobacillus rhamnosus CRL1505 and its peptidoglycan improve systemic and respiratory innate immune response during recovery of immunocompromised-malnourished mice.

The effect of non-viable Lactobacillus rhamnosus CRL1505 and its cell wall and peptidoglycan on respiratory immunity in malnourished mice was studied. Weaned mice were malnourished with a protein-free diet for 21d and received BCD during 7d (BCD) or BCD with nasal non-viable L. rhamnosus CRL1505 (BCD+UV) or its cell wall (BCD+CW) or peptidoglycan (BCD+PG) supplementation during last 2d of the treatment. Malnourished mice without treatment (MNC) and well-nourished mice (WNC) were used as controls. Mice were infected nasally with Streptococcus pneumoniae after treatments. Resistance against pneumococci was reduced in MNC mice. Repletion with BCD reduced lung and blood bacterial cell counts when compared to MNC mice but the counts did not reach the levels of the WNC group. However, when malnourished mice received BCD+UV, BCD+CW or BCD+PG, pneumococci was not detected in lung or blood samples. Pneumococcal infection increased the levels of TNF-α, IL-1ß, IL-6, and IL-10 in the respiratory tract, however the values were lower in MNC than in WNC mice. BCD+UV and BCD+PG groups showed values of phagocytes, IL-1ß and IL-6 that were similar to WNC mice, while TNF-α was significantly higher in those groups when compared to WNC mice. Moreover, BCD+UV and BCD+PG treatments improved levels of respiratory IL-10, reaching values that were superior to those observed in WNC mice. The work demonstrates for the first time that non-viable probiotic bacteria or their cellular fractions could be an interesting alternative as mucosal immunomodulators, especially in immunocompromised hosts in which the use of live bacteria might be dangerous.