Gastrointestinal Tract UPDATES

Bioavailability —

The British Journal of Nutrition has a very good Supplement on The Nutritional Needs of Children
BJN 2007, vol 92, pp S 67-S 232 Editors Koletko B, et al
In deciding how much should of a nutrient be recommended it is important to define Nutrient Handling.
This is an interesting concept and identifies the different variables when food and its constituents are eaten.
1. Dietary intake (of foods or nutrient mixtures); impact of processing and preparation.
2. Milieu within the gastrointestinal tract (matrix effects, intraluminal nutrient interactions, gut transit time).
3. Mucosal binding.
4. Mucosal cell uptake.
5. Mucosal export (portal circulation or mesenteric lymphatic transport).
6. Hepatic uptake.
7. Organ (including liver) clearance.
8. Biliary clearance and excretion.
9. Systemic circulation and peripheral distribution.
10. Renal clearance and excretion.
11. Peripheral tissue utilisation (e.g. metabolic/catabolic use. structural roles) and deposition.
Each nutrient can then be individually assigned one or more of these key steps as being rate-limiting for its utilisation.

Another variable will be age as these variable will be different at different ages of development.

However I was very interest ed to note that a very important variable the speed and length of time spent eating was not mentioned. This is an enormous variable and very neglected, by all but the traditional French eaters.

Faecal bacteria —

The microbiome , that is the pool of micro-organism living in our bodies generally live harmoniously with us, and form a second genome. Reports in Science, a team from the International Human Microbiome Consor¬tium (Nelson et al. and Qin et al describe the -genome sequence of the bacterial species from the human microbiome.

The contribution made by microorganisms to the human body is very important. Some 1.5 kilograms of bacteria colonize the human gut, with others inhabiting the external and internal surfaces of the body. Only only 10% of the total number of cells in the human body consists of human cells, with the rest coming from symbiotic bacterial cells.

Molecules produced by the gut bacteria can enter the bloodstream via either a normal anatomical route, the enterohepatic cir¬culation or through a partially damaged gut barrier. Beneficial gut bacteria can produce anti-inflammatory factors, pain-relieving compounds, antioxidants and vitamins to protect and nurture the body. Conversely, harmful bacteria may deregulate genes mediating energy metabolism, and can produce toxins that mutate DNA, affecting the nervous and immune systems. The outcome is various forms of chronic disease, including obesity, diabetes and even cancers. This exchanging of nutrients and metabolic wastes, makes symbiotic bacteria a human organ and their collective genomes our second genome.

The human gut micro¬biome contains around 1,000 bacterial species. Nelson et al. of the Human Microbiome Iumpstart Reference Strains Consortium report an initial reference-genome sequencing for 178 microbial species. These are mostly from the gut, but also from the oral cavity, urogenital/vaginal tract, skin, respiratory tract and even blood.

The ultimate test of the The International Human Microbiome Con¬sortium is to capture the diversity of the microbiome relevant to human health.

The gut microbiome may vary extensively among people from different ethnic groups.

Individual strains of a bacterial species can differ by up to 30% in terms of genetic sequence. The genomes of human and mouse differ by only 10%, the genetic and functional diversity within the same bacterial species can be over¬whelmingly high. Nelson et al. show that sequencing different strains of the same species may greatly increase the discovery of new genes
In sequencing one genomically distant strain of the bacterium Bifidobacterium iongum, the authors added 640 new genes to the pan-genome of this species, Four sequenced strains (the pan-genome is all the genes found in the sequenced strains of one species). By comparison, the core genome of these strains contains just 1,430 genes (the core genome is the genes shared by all sequenced strains in a species). For many gut bacterial spe¬cies, therefore, more strains must be sequenced before we can decipher their pan-genome.

Another obstacle to completing the refer¬ence-genome set is that some strains that are relevant to hwnan health and disease cannot be maintained in culture.

A complex business. Not yet open to quick judgements. Of great interest to nutritionists. But not obligatory. We can live very well without a colon. Zhao 2010 The tale of our other gneome nature vol 465 pp 879-90

Faecal bacteria in Japanese —

Marine algae contain sulphated polysaccharides that are absent in terrestrial plants. These unique polymers are used as a carbon source by marine heterotrophic bacteria that produce specific CAZymes. In comparison to the accumulating knowledge on the degradation of plant polysaccharides little is known about the enzymes acting on polysaccharides from marine edible algae such as Porphyra (nori), Ulva (sea lettuce) or Undaria (wakame).

Gut microbes supply the human body with energy from dietary polysaccharides through carbohydrate active enzymes, or CAZymes, which are absent in the human genome. These enzymes target polysaccharides from plants that dominated diet throughout human evolution

The array of CAZymes in gut microbes is highly diverse, exemplified by the human gut symbiont Bacteroides thetaiotaomicron, which contains 261 glycoside hydrolases and polysaccharide lyases, as well as 208 homologues of susC and susD-genes coding for two outer membrane proteins involved in starch utilization.

The question of how this diversity evolved by acquiring new genes from microbes living outside the gut. In this paper by Hehemann et al in Nature April 2010 the authors characterize the first porphyranases from a member of the marine Bacteroidetes, Zobellia galactanivorans, active on the sulphated polysaccharide porphyran from marine red algae of the genus Porphyra. They show that genes coding for these porphyranases, agarases and associated proteins have been transferred to the gut bacterium Bacteroides plebeius isolated from Japanese individuals

Their comparative gut metagenome analyses show that porphyranases and agarases are frequent in the Japanese population and that they are absent in metagenome data from North American individuals.

Seaweeds make an important contri¬bution to the daily diet in Japan (14.2 g per person per day), and Porphyra spp. (nori) is the most important nutritional seaweed, traditionally used to prepare sushi

This indicates that seaweeds with associated marine bacteria may have been the route by which these novel CAZymes were acquired in human gut bacteria, and that contact with non-sterile food may be a general factor in CAZyme diversity in human gut microbes.

Hehemann et al 2010 Transfer of carbohydrate-active enzymes from marine bacteria to Japanese gut microbiota Nature vol 464 pp 908-912

Sonneburg Genetic pot luck 2010 Nature vol 464 837-8

Faecal virus —

The variety of Viruses and their life cycles are poorly understood in the human gut and other body habitats.

Phages and their encoded functions may provide information of a human microbiota and of microbial community responses to various disturbances.
This paper reports sequencing of the viromes (metagenomes) of virus-like particles isolated from faecal samples collected from healthy adult female monozygotic twins and their mothers at three time points over a one-year period. They compared these results sets with data sets of sequenced bacterial16S ribosomal RNA genes and total-faecal-community DNA.

The co-twins and their mothers share a significantly greater degree of similarity in their faecal bacterial communities than do unrelated individuals. In contrast, viromes are unique to individuals regardless of their degree of genetic relatedness. Despite remarkable interpersonal variations in viromes and their encoded functions, intra personal diversity is very low, with >95% of virotypes retained over the period surveyed, and with viromes dominated by a few temperate phages that exhibit remarkable genetic stability.

Reyes et al 2010 Viruses in the faecal microbiota of monozygotic twins and their mothers Nature vol 466 pp 334-338

Intestinal Stem Cells —

The intestinal epithelium is the most rapidly self-renewing tissue in adult mammals. The absorptive epithelium of the small intestine is ordered into crypts and villi, which in the mouse turn over every three to five days. The rapid rate of ceil production in the crypts is balanced by apoptosis at the tips of the villi.

Self-renewing stem cells cycle steadily to produce the cells capable of differentiating towards all types of intestinal cells. The estimated number of stem cells is between four and six per crypt:. Long-term DNA-label retention has tentatively located stem cells directly above the Paneth cells’. Three differentiated cell types (enterocytes, goblet cells and enteroendocrine cells) form from trans it-amplifying cells at the crypt-villus junction and continue their migration in coherent bands stretching along the crypt-villus axis. Each villus receives cells from multiple different crypts. The fourth principal differentiated cell type, the Paneth cell, is at bottom of the crypt

The colon epithelium contains crypts, but has a flat surface rather than carrying villi. This epithelium consists of two main differentiated cell types: the absorptive colonocytes and the goblet cells’. Until now, no stem cells have been identified in the colon.

Using an intestinal target gene Lgr5 Barker et al have demonstrated that the crypt base columnar cell generated all epithelial lineages over a 60-day period, suggesting that it represents the stem cell of the small intestine and colon. Barker et al. ( 2007 ) Identification of stem cells in small intestine and colon by marker gene Lgr5 Nature vol 449, 1003-7

Particles in the Diet —

Dietary microparticles and their impact on tolerance and immune responsiveness of the gastrointestinal tract

Powell et al (2007 ) Dietary microparticles and their impact on tolerance and immunre responsiveness of the gastrointestinal tract British Nutriton Journal 98, suppl 1 S 59-63

This is an interesting and novel approach to an important contribution to a theory for the aetiology of Crohns disease. Crohns disease is said to be a new condition. Who knows? One theory was that toothpaste and other sources of indigestible particles is a factor. So the authors have reviewed the evidence.

Dietary microparticles are non-biological bacterial-sized particles of the gastrointestinal lumen that occur due to endogenous formation (calcium phosphate) or following oral exposure (exogenous microparticlc). In the UK about 40 mg (10 12) of exogenous microparticles are ingested per person per day, through exposure to food additives, pharmaceutical/supplement excipients or toothpaste constituents.

Once ingested, exogenous micro particles are unlikely to pass through the gastrointestinal tract without adsorbing to their surfaces some ions and molecules of the intestinal lumen. Both entropy and ionic attraction drive such interactions. Calcium ions are especially well adsorbed by dietary micro particles which then provide a positively charged surface for the attraction (adsorption) of other organic molecules such as lipopolysaccharides, peptidoglycans or protein antigen from the diet or commensal flora.

The major (but not only) sites of microparticle entry into intestinal tissue arc the M-cell rich lymphoid aggregates (termed Peyer’s patches in the small bowel). Indeed, it is well established that this is an efficient transport route for non-biological microparticles although it is unclear why.

The authors suggest that this pathway exists for “endogenous microparticles” of calcium phosphate. with immunological and physiological benefit, and that “exogenous dietary microparticles”, such as titanium dioxide and the silicates, hijack this route.

This overview focuses on what is known of these microparticles and outlines their potential rule in immune tolerance of the gut (endogenous microparticlesl or immune activation (exogenous microparticles) and inflammation of the gut.


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