probiotics, prebiotics and the gut microbiota - International Life ...

8 Concise Monograph SeriesBacteria also metabolise other components found intheir environment (Figure 2). In addition to foodstuffsconsumed by the host and not fully digested, substratesfor bacterial growth include degraded bacterial cells andhost-derived mucins, enzymes and sloughed-off intestinalcells. Peptococci and clostridia species metabolise proteinsas a source of nitrogen for growth and yield branchedchain fatty acids such as isobutyrate and isovalerate aswell as a range of nitrogenous and sulphur-containingcompounds, some of which may be harmful. For example,ammonia, amines and phenolic compounds can, undercertain conditions, lead to the formation of carcinogens,particularly in the left, descending colon where putrefactiveconditions can prevail. Phytochemicals such as isoflavonesand polyphenols may also be metabolised, yielding smallercomponents like equol and small phenolic molecules thatare more readily absorbed. The impact of this microbialactivity on human health is still under investigation.As bacteria grow in numbers, they contribute to the bulkof the stools that form in the rectum. High stool bulk isrelated to a shorter gut transit time and also to a lowerrisk of constipation and bowel cancer. Although nonfermentabledietary fibre sources such as wheat bran fibreare the most important contributors to stool bulk, bacterialmass resulting from the fermentation of more solubledietary fibres and carbohydrate residues also contributesto the bulk.The GI epithelial barrier and immunesystemThe GI tract is sometimes described as the body’s largestimmune organ. It represents the host’s greatest areaof mucosal contact with the environment and containsas many as 80% of all antibody-producing cells. Theintestinal microbiota is also a vital part of the body’sdefence system.At birth, the GI tract is essentially sterile and, in addition, thenewborn’s immune system is not fully mature. The immunesystem only becomes functionally mature as a result ofexposure to the myriad of foreign substances encounteredby the naive intestinal tract. Studies on animals raised ingerm-free conditions have shown that the immune systemis poorly developed in such animals and that they havelower levels of immunoglobulins and fewer specialisedimmune cells in their intestinal mucosa. Germ-free animalsare thus much more susceptible to disease than are thosethat are conventionally reared. It is also known from thesestudies that microbial antigens, derived from the intestinalmicrobiota as well as the environment, play a crucial role inthe maturation of gut-associated lymphoid tissue (GALT)and normal resistance to disease.The GALT is organised into different compartments suchas lymph nodes, lymph follicles and Peyer’s patches(Figure 3). The GALT limits the passage of bacteriaand food antigens from the GI lumen through theintestinal mucosa. It does, however, allow the passageof antigens (minute samples of viable or dead bacteriaand protein and peptide fragments) using specialisedcells such as the M cells that cover the Peyer’s patchesand the dendritic cells that act as sentinels along themucosa. These so-called antigen-presenting cells (APCs)process and present the antigens to lymphocytes, atype of immune cell. The APCs are thus very importantin stimulating a balanced immune response and, as isincreasingly documented, having an impact beyond thegut (see the section “Cross-talk with the host”). It hasbeen hypothesised that reduced exposure to exogenousmicrobes in developed and industrialised countries hasled to increased incidence of chronic immune dysfunction,leading to atopic (allergic) and auto-immune disorders orinflammatory bowel disease, because of changes in theway the immune system has matured. This is known asthe “hygiene hypothesis”.