Dietary carbohydrates have the potential to influence diverse functional groups of bacteria within the human large intestine. Of 12 Bifidobacterium strains of human gut origin from seven species tested, four grew in pure culture on starch and nine on fructo-oligosaccharides. The potential for metabolic cross-feeding between Bifidobacterium adolescentis and lactate-utilizing, butyrate-producing Firmicute bacteria related to Eubacterium hallii and Anaerostipes caccae was investigated in vitro. E. hallii L2-7 and A. caccae L1-92 failed to grow on starch in pure culture, but in coculture with B. adolescentis L2-32 butyrate was formed, indicating cross-feeding of metabolites to the lactate utilizers. Studies with [13 C]lactate confirmed carbon flow from lactate, via acetyl coenzyme A, to butyrate both in pure cultures of E. hallii and in cocultures with B. adolescentis. Similar results were obtained in cocultures involving B. adolescentis DSM 20083 with fructo-oligosaccharides as the substrate. Butyrate formation was also stimulated, however, in cocultures of B. adolescentis L2-32 grown on starch or fructo-oligosaccharides with Roseburia sp. strain A2-183, which produces butyrate but does not utilize lactate. This is probably a consequence of the release by B. adolescentis of oligosaccharides that are available to Roseburia sp. strain A2-183. We conclude that two distinct mechanisms of metabolic cross-feeding between B. adolescentis and butyrate-forming bacteria may operate in gut ecosystems, one due to consumption of fermentation end products (lactate and acetate) and the other due to cross-feeding of partial breakdown products from complex substrates.Microbial growth and metabolism in the human large intestine depend to a large extent on the supply of dietary carbohydrates that resist digestion in the upper gut. The fermentation of these compounds, which include plant cell wall polysaccharides and some storage polysaccharides and oligosaccharides, has a major influence on health (9, 20, 43). Indeed, specific carbohydrates are now widely used as functional foods and as prebiotics, based on the concept that they stimulate particular gut bacteria that promote gut health (18) and, at the same time, reduce the populations of nonutilizing bacteria through competition. Inulin and fructo-oligosaccharides (FOS), for example, were originally proposed as prebiotics that selectively stimulate bifidobacteria. While there is evidence that this occurs (11,19,26,45), other studies, using molecular techniques, have revealed that a variety of other bacterial groups, including clostridium-related species, also respond to inulin or FOS supplied as prebiotics in either fermentor experiments or animal models (13, 25).Among the possible explanations for this diversity in response to prebiotics is that complex gut microbial communities involve extensive metabolic interactions (10, 46). Metabolic products produced from dietary prebiotics by one bacterial species may then provide substrates to support growth of other populations, and this i...

We conclude that human placental 11 beta-HSD plays a crucial role in controlling glucocorticoid access to the fetus. Other enzymes are not significant contributors at physiologically relevant cortisol concentrations.

Acetate is normally regarded as an endproduct of anaerobic fermentation, but butyrate-producing bacteria found in the human colon can be net utilisers of acetate. The butyrate formed provides a fuel for epithelial cells of the large intestine and influences colonic health. [1-13 C]Acetate was used to investigate the contribution of exogenous acetate to butyrate formation. Faecalibacterium prausnitzii and Roseburia spp. grown in the presence of 60 mM-acetate and 10 mM-glucose derived 85 -90 % butyrate-C from external acetate. This was due to rapid interchange between extracellular acetate and intracellular acetyl-CoA, plus net acetate uptake. In contrast, a Coprococcus-related strain that is a net acetate producer derived only 28 % butyrate-C from external acetate. Different carbohydrate-derived energy sources affected butyrate formation by mixed human faecal bacteria growing in continuous or batch cultures. The ranking order of butyrate production rates was amylopectin . oat xylan . shredded wheat . inulin . pectin (continuous cultures), and inulin . amylopectin . oat xylan . shredded wheat . pectin (batch cultures). The contribution of external acetate to butyrate formation in these experiments ranged from 56 (pectin) to 90 % (xylan) in continuous cultures, and from 72 to 91 % in the batch cultures. This is consistent with a major role for bacteria related to F. prausnitzii and Roseburia spp. in butyrate formation from a range of substrates that are fermented in the large intestine. Variations in the dominant metabolic type of butyrate producer between individuals or with variations in diet are not ruled out, however, and could influence butyrate supply in the large intestine.

The effects of either low (25 pnollmin) or high (235 pnol/min) infusion of NH&l into the mesenteric vein for 5 d were determined on 0, consumption plus urea and amino acid transfers across the portaldrained viscera (PDV) and liver of young sheep. Kinetic transfers were followed by use of l5NH4C1 for 10 h on the fifth day with simultaneous infusion of [l-'3C]leucine to monitor amino acid oxidation.Neither PDV nor liver blood flow were affected by the additional NH, loading, although at the higher rate there was a trend for increased liver 0, consumption. N&-N extraction by the liver accounted for 64-70 % of urea-N synthesis and at the lower infusion rate the additional N required could be more than accounted for by hepatic removal of free amino acids. At the higher rate of NH, administration additional sources of N were apparently required to account fully for urea synthesis. Protein synthesis rates in the PDV and liver were unaffected by NH3 infusion but both whole-body (P < 0.05) and splanchnic tissue leucine oxidation were elevated at the higher rate of administration. Substantial synthesis of [15wglutamine occurred across the liver, particularly with the greater NH, supply, and enrichments exceeded considerably those of glutamate. The [15N]urea synthesized was predominantly as the single labelled, i.e. [14N15N], species. These various kinetic data are compatible with the action of ovine hepatic glutamate dehydrogenase (EC1.4.1.2) in periportal hepatocytes in the direction favouring glutamate deamhation. Glutamate synthesis and uptake is probably confined to the perivenous cells which do not synthesize urea. The implications of NH, detoxification to the energy and N metabolism of the ruminant are discussed.

This study demonstrates that certain microbial species have the ability to ferment all three AAAs and that protein fermentation is the likely source of major phenylpropanoid-derived metabolites in the colon.