Preclinical evaluation of probiotics and prebiotics as modulators of the immune function in early life
- Autores: Ignasi Azagra Boronat
- Directores de la Tesis: Francisco José Pérez Cano (dir. tes.), Maria José Rodriguez Lagunas (codir. tes.)
- Lectura: En la Universitat de Barcelona ( España ) en 2020
- Idioma: español
- Tribunal Calificador de la Tesis: Albert Bosch i Navarro (presid.), María Carmen Collado Amores (secret.), Adele Costabile (voc.)
- Programa de doctorado: Programa de Doctorado en Alimentación y Nutrición por la Universidad de Barcelona
- Materias:
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- Resumen
It is well known that maternal breast milk contains bioactive compounds that help infants to acquire immunity. Among these bioactive compounds, human milk oligosaccharides (HMOs) have been shown to have prebiotic properties and several bacteria from breast milk have been isolated and used as probiotics. Nowadays many mothers feed their infants with infant formula, although it is well known that breast milk is the gold standard in infant nutrition. Therefore, it would be of interest to test specific probiotics and prebiotics already present or similar to those found in breast milk in order to provide the infant with the best nutrition and protection against diseases. Moreover, it would also be interesting to know if administration of probiotics to the mother can also benefit their offspring.
Therefore, this thesis aimed to establish the immunomodulatory activity of probiotics and prebiotics at preclinical level in the context of health and infection in early life.
Firstly, the modulatory activity of 2’-fucosyllactose (2’-FL), the most abundant HMO found in breast milk, was tested in healthy suckling rats. 2’-FL promoted the maturation of their immune system. In addition, the intestinal concentrations of cytokines were reduced in a similar manner breast-fed infants have shown compared to formula-fed infants. Additionally, this HMO increased intestinal villi growth. Finally, a prebiotic effect was also identified because 2’-FL increased the proportion of Lactobacillus and butyrate.
Then, the modulatory activity of 2’-FL was tested in the context of rotavirus (RV) infection, one of the most common diarrheal diseases in infancy. Moreover, a mixture of short chain galactooligosaccharides and long chain fructooligosaccharides (GOS/FOS) at a 9:1 ratio and their combination with 2’-FL were also tested. The three supplementations evidenced clinical amelioration of RV-induced diarrhea in suckling rats. 2’-FL seemed to strengthen the intestinal barrier, whereas GOS/FOS evidenced an intestinal trophic effect and RV blocking activity. The combination kept the activities found for both prebiotics separately and showed additive effects in several variables. Finally, the three supplementations seemed to avoid the dysbiosis induced by RV and to promote a healthier microbiota, for example by increasing butyrate-producing bacteria.
The present thesis also screened for the effects of Lactobacillus and Bifidobacterium probiotic strains in the RV diarrhea model in suckling rats. L. acidophilus NCFM was highly effective at reducing the severity and incidence of diarrhea, and also B. breve M-16V and L. helveticus R0052. Only Lactobacillus strains were able to reduce the RV elimination compared to RV group. L. salivarius PS2 did not influence the normal course of the RV disease, suggesting that not all probiotic strains are useful to prevent RV diarrhea.
Finally, the influence of Lactobacillus fermentum CECT5716 supplementation to dams during pregnancy and lactation periods was studied. After administration, the strain was detected in the cecal content of dams receiving the probiotic and in some of their breast milk samples and cecal contents of their pups, suggesting the existence an entero-mammary route. Moreover, probiotic administration increased IgA content and changed the fatty acid (FA) profile in breast milk, for example by increasing the proportion of total polyunsaturated FAs. Interestingly, the amount of IgA was also increased in the gut of the offspring. All these effects seemed to be independent of the arrival of the probiotic strain to the breast milk or to the pups. Overall, probiotic administration to the mother seems to be a good strategy to promote immunity in the offspring.
Although some evidence of the mechanisms of action of probiotics and prebiotics in early life was revealed, further studies are needed to better understand their function and to recommend their inclusion in infant formulas or use them as supplements.
