The bacteria located within the human gastrointestinal tract (the gut microbiota) perform numerous protective, immunological and metabolic functions for the host. They are increasingly implicated in the pathogenesis of acquired inflammatory diseases of the gut in childhood, namely: necrotising enterocolitis (NEC) and inflammatory bowel disease (Crohn’s disease (CD) and ulcerative colitis (UC)). Study of the role that the microbiota may play in the development of such diseases may lead to new therapies to modulate or even cure them. However many current techniques depend on the ability to study such bacteria outwith their natural ecosystem. Although molecular techniques can identify species independent of standard cultures they can enlighten little on the metabolic activity of identified bacterial species, which may be important in the propagation of inflammatory responses. Little is known about the potential of novel therapeutic strategies, such as probiotics, to modulate diseases such as NEC. In addition inadequate scientific rigour has been applied to the science of probiotics. The aims of the study described in this dissertation were to test the following hypotheses. Hypotheses:1.Probiotics prevent NEC in at risk infants of very low birth weight (VLBW).2.The human gut microbiota can be labelled by stable isotope probing (SIP) to measure metabolic activity.3.Quantitative measurement of the metabolic activity of the unculturable gut microbiota is a useful way of studying changes in the microbiota, compared with measures of bacterial diversity, and may enlighten our understanding of bacterially mediated inflammatory stimuli in inflammatory gut diseases of childhood.
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The role of the gut microbiota in inflammatory diseases of childhood
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