About 500 different species of bacteria colonize the gastro-intestinal tract, in an amount equal to 1000 billion lire / gram, giving life commensal microbial ecosystem, the dimensions of which make it a real organ metabolically active. The intestinal microflora, which resides primarily in the colon, performs very important functions for the health of our organism as the synthesis of vitamins, fatty acids (butyrate and proprionate) and amino acids, but is also able to interact with the mucosal barrier and the system Local immune. The normal intestinal mucosa is constantly exposed to an enormous antigen load in the lumen, where the resident bacterial flora contributes impressive. Indeed, inflammation is a normal phenomenon in the intestine, a so-called "physiological inflammation", as the commensal bacteria stimulate the immune system regularly. When the structure for maintaining immune homeostasis are not working properly we move to a situation of inflammation is not controlled and the onset of inflammatory bowel disease, although, due to the complexity of the microbiota, is not yet clear the role played by commensal bacteria, and those pathogens. IBD, such as Crohn's disease and ulcerative colitis, are immune-mediated disorders because they cause an abnormal immune response and cause chronic inflammation at the level of the gastro-intestinal tract, with symptoms such as abdominal pain, diarrhea and loss of blood. Recently it has been isolated from the intestinal tract, a new bacterium called Akkermansia muciniphila belongs to the genus Verrucomicrobia. Akkermansia muciniphila is a Gram-negative, strictly anaerobic, not mobile asporogenous shaped coconut or rod with an unusual structure, , with wart-like protrusions phones, able to grow singly or in pairs. My work has focused on depth phenotypic characteristics (sugar metabolism and enzyme activity) and antibiotic resistance of A. muciniphila, germ until now little known. The presence of A. muciniphila in humans is associated with a good balance of the intestinal microflora and thus able to perform a beneficial action in the host organism. In order to substantiate these claims, it was decided to study the role of A. muciniphila in animal models of intestinal inflammation induced by dextran sulfate sodium (DSS). The animals were divided into groups: the first group was administered the germ vivo, the second dead one, while the control group was administered only water. It was subsequently induced experimental colitis. To analyze the trend of the disease were taken into account three basic parameters: body weight, weight of the colon and DAI (disease activity index). The results of this monitoring show that A. muciniphila is able to protect the animals from the typical symptoms of the colitis, which affect, however, those not treated. The analysis of cytokines appears to confirm the protective function of the bacterium during demonstrations inflammatory bowel, because the expression of cytokines during colitis presents lower levels in animals pre-treated with Akkermansia muciniphila alive. In conclusion, it is clear that this new germ Akkermansia muciniphila is one of those responsible for the contribution beneficial intestinal bacteria and appears to have an important immunomodulatory role in inflammatory bowel models: the data show that the germ is present in the normal intestinal microflora of individuals adults, is able to play a beneficial role in the course of IBD. This promising result allows us to hope that A. muciniphila can be used in future as an excellent therapeutic target in the treatment of inflammatory bowel disease.

Potenzialità immunomodulanti di Akkermansia muciniphila in modelli animali di inflammatory bowel disease (IBD)

Russo, Valentina
2016-02-10

Abstract

About 500 different species of bacteria colonize the gastro-intestinal tract, in an amount equal to 1000 billion lire / gram, giving life commensal microbial ecosystem, the dimensions of which make it a real organ metabolically active. The intestinal microflora, which resides primarily in the colon, performs very important functions for the health of our organism as the synthesis of vitamins, fatty acids (butyrate and proprionate) and amino acids, but is also able to interact with the mucosal barrier and the system Local immune. The normal intestinal mucosa is constantly exposed to an enormous antigen load in the lumen, where the resident bacterial flora contributes impressive. Indeed, inflammation is a normal phenomenon in the intestine, a so-called "physiological inflammation", as the commensal bacteria stimulate the immune system regularly. When the structure for maintaining immune homeostasis are not working properly we move to a situation of inflammation is not controlled and the onset of inflammatory bowel disease, although, due to the complexity of the microbiota, is not yet clear the role played by commensal bacteria, and those pathogens. IBD, such as Crohn's disease and ulcerative colitis, are immune-mediated disorders because they cause an abnormal immune response and cause chronic inflammation at the level of the gastro-intestinal tract, with symptoms such as abdominal pain, diarrhea and loss of blood. Recently it has been isolated from the intestinal tract, a new bacterium called Akkermansia muciniphila belongs to the genus Verrucomicrobia. Akkermansia muciniphila is a Gram-negative, strictly anaerobic, not mobile asporogenous shaped coconut or rod with an unusual structure, , with wart-like protrusions phones, able to grow singly or in pairs. My work has focused on depth phenotypic characteristics (sugar metabolism and enzyme activity) and antibiotic resistance of A. muciniphila, germ until now little known. The presence of A. muciniphila in humans is associated with a good balance of the intestinal microflora and thus able to perform a beneficial action in the host organism. In order to substantiate these claims, it was decided to study the role of A. muciniphila in animal models of intestinal inflammation induced by dextran sulfate sodium (DSS). The animals were divided into groups: the first group was administered the germ vivo, the second dead one, while the control group was administered only water. It was subsequently induced experimental colitis. To analyze the trend of the disease were taken into account three basic parameters: body weight, weight of the colon and DAI (disease activity index). The results of this monitoring show that A. muciniphila is able to protect the animals from the typical symptoms of the colitis, which affect, however, those not treated. The analysis of cytokines appears to confirm the protective function of the bacterium during demonstrations inflammatory bowel, because the expression of cytokines during colitis presents lower levels in animals pre-treated with Akkermansia muciniphila alive. In conclusion, it is clear that this new germ Akkermansia muciniphila is one of those responsible for the contribution beneficial intestinal bacteria and appears to have an important immunomodulatory role in inflammatory bowel models: the data show that the germ is present in the normal intestinal microflora of individuals adults, is able to play a beneficial role in the course of IBD. This promising result allows us to hope that A. muciniphila can be used in future as an excellent therapeutic target in the treatment of inflammatory bowel disease.
Immunomodulant potentiality of Akkermansia muciniphila in animal models of inflammatory bowel disease (IBD)
10-feb-2016
File in questo prodotto:
File Dimensione Formato  
Tesi_V_Russo.pdf

accesso aperto

Tipologia: Tesi di dottorato
Dimensione 1.85 MB
Formato Adobe PDF
1.85 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11695/66363
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact