RESUMEN
BACKGROUND: Imbalance of the human gut microbiota in childhood, mainly due to low gut biodiversity and a low bifidobacterial load, has been suggested as a risk factor for atopy. Administration of Enterococcus faecium L3 in infants has been shown to increase the gut bifidobacterial count. The aim was to verify if a mixture of Bifidobacterium animalis subsp. lactis BB12 and E. faecium L3 could reduce the signs, symptoms and need for drugs in atopic children. METHODS: We retrospectively analyzed, and compared with controls, clinical outcomes following use of BB12 and L3 strains when administered 3 months before or during the development of signs and symptoms of atopy. RESULTS: When administered in the 3 months before the development of atopy, the BB12 and L3 strains significantly reduced (P<0.001) rhinitis, watery eyes and cough/bronchospasm. However, reduced efficacy was observed when the mixture was given during the 3 months of atopy. The mixture of strains also significantly reduced the use of oral antihistamines, inhaled corticosteroids (in the same children in two different years) and oral corticosteroids (in different children in the same year). CONCLUSIONS: When administered as a prophylactic, the mixture of BB12 and L3 (iNatal Ped®) statistically decreases the signs and symptoms of atopy and reduces the use of drugs. Administration of the same probiotics as treatment after the appearance of atopy is less effective.
Asunto(s)
Bifidobacterium animalis , Enterococcus faecium , Hipersensibilidad/terapia , Probióticos/administración & dosificación , Adolescente , Corticoesteroides/administración & dosificación , Niño , Preescolar , Femenino , Microbioma Gastrointestinal , Antagonistas de los Receptores Histamínicos/administración & dosificación , Humanos , Hipersensibilidad/inmunología , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Glucocorticoids (GCs) are commonly used to treat autoimmune and inflammatory diseases, but their clinical effects and long-term use can lead to serious side effects. New drugs that can replace GCs are needed. Glucocorticoid-induced leucine zipper (GILZ) is induced by GCs and mediates many of their anti-inflammatory effects, such as inhibiting the pro-inflammatory molecule NF-κB. The GILZ C-terminal domain (PER region) is responsible for GILZ/p65NF-κB interaction and consequent inhibition of its transcriptional activity. A set of five short peptides spanning different parts of the PER region of GILZ protein was designed, and their anti-inflammatory activity was tested, both in vitro and in vivo. We tested the biological activity of GILZ peptides in human lymphocytic and monocytic cell lines to evaluate their inhibitory effect on the NF-κB-dependent expression of pro-inflammatory cytokines. Among the tested peptides, the peptide named PEP-1 demonstrated the highest efficacy in inhibiting cell activation in vitro. Subsequently, PEP-1 was further evaluated in two in vivo experimental colitis models (chemically induced by DNBS administration and spontaneous colitis induced in IL-10 knock-out (KO) mice (to assess its effectiveness in counteracting inflammation. Results show that PEP-1 reduced disease severity in both colitis models associated with reduced NF-κB pro-inflammatory activity in colon lamina propria lymphocytes. This study explored GILZ-based 'small peptides' potential efficacy in decreasing lymphocyte activation and inflammation associated with experimental inflammatory bowel diseases (IBDs). Small peptides have several advantages over the entire protein, including higher selectivity, better stability, and bioavailability profile, and are easy to synthesize and cost-effective. Thus, identifying active GILZ peptides could represent a new class of drugs for treating IBD patients.