Role of Intestinal Microbiota in Ulcerative Colitis

Theoretical part
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4. Modulation of the gut microbiota
maintaining a normal IEC populations thereby preventing mutations (Topping and Clifton, 2001)
and has shown to alter cytokine production towards a regulatory profile in vitro (Millard et al.,
2002). Both propionate and butyrate have shown to significantly decrease expression of invasion
genes in Salmonella typhimurium (Lawhon et al., 2002). It has recently been demonstrated that
acetate, propionate, and butyrate are able to inhibit TNFα‐mediated activation of the NF‐κB
pathway in human colon adenocarcinoma cell lines and induce anti‐inflammatory activity in an in
vitro model of murine experimental colitis (Tedelind et al., 2007).
4.4. Metabolic cross-feeding
In a complex microbial community such as the gut extensive metabolic interactions occur.
Metabolic products produced from non‐digestible poly‐ or oligosaccharide by one bacterial species
may provide substrates to support growth of another. This metabolic cross‐feeding can have
metabolic consequences, because the route of the substrate is not completely obvious (Belenguer
et al., 2006;Flint et al., 2007). An example of inter‐relatedness, which could benefit the host, is the
formation of butyrate by metabolic cross‐feeding. Fermentation of FOS seems to be mainly
performed by lactate and acetate producing bacteria rather than butyrate producing bacteria
(Damian et al., 1999). However, Morrison et al. (2006) have shown that FOS can selectively
stimulate the bacterial conversion of acetate and lactate to butyrate. In line with this, in vitro
fermentation studies have demonstrated that butyrate‐producing species such as Eubacterium
hallii and Anaerostipes caccae, who are not able to grow on FOS in pure cultures, can utilize the
fermentative products lactate and acetate to produce butyrate in co‐culturing with FOS‐degrading
Bifidobacterium strains (Duncan et al., 2003;Belenguer et al., 2006). However, metabolic cross‐
feeding can also give rise to unfavourable stimulation of bacteria and metabolites. A predominant
sulphate‐reducing species, which inhabit the human colon, is Desulfovibrio piger (Fite et al., 2004).
D. piger utilize lactate as a preferred co‐substrate, which is oxidized to acetate, while sulphate is
reduced to sulphide (Loubinoux et al., 2002). It has recently been demonstrated that D. piger
could compete for lactate produced at relatively low concentrations by B. adolescentis in co‐
cultures with either E. Hallii or A. caccae. Production of butyrate by E. Hallii and A. caccae was
inhibited by 50%, however, sulphide production by D. piger was unaffected by the presence of
butyrate‐producing bacteria (Marquet et al., 2009). A high concentration of sulphide is believed to
be toxic to IECs and may create cellular energy deficiency in IECs by inhibiting the β‐oxidation of