The Intestinal Flora of Man

In 1907 Schmidt, reviewing the existing knowledge at that time, stated that the chemical processes which occur in the decomposition of the chyme 

Schmidt in Van Noorden, Metabolism and Practical Medicine, Wm. Heine-mann, London, 1907, Vol. 2, p. 169. 

The term putrefactive later gave way to proteolytic, but this did not clarify matters, for no sharp distinction has apparently be made between proteolytic and saccharolytic bacteria, at least in the feces.  

Although vitamin synthesis will be discussed elsewhere, it should be noted that just as the bacteria of the ruminant and other herbivores synthesize vitamins in substantial amounts, so it is highly probable that in man vitamins K, B complex, and E are synthesized in amoimts which help to meet requirement. Indeed some evidence for this already exists. On the other hand, certain intestinal bacteria destroy vitamins, e.g., vitamin C and nicotinic acid. 

In rats it has been found that the giving of large quantities of lactose or dextrin in the diet can cause the intestinal flora so to change that it contains 90% or more of aciduric bacilli. These two carbohydrates are acted upon very slowly and consequently probably pass to the large intestine where they are acted upon by the aciduric bacilli— notably Lactobacillus acidophilus— with the formation of a large amount of lactic acid the presence of this acid is said to be unfavorable to the persistence of the proteolytic bacteria. 

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The intestinal lumen of animals and man always contains a rich bacterial flora. The exact composition of the bacterial flora is known only qualitatively and includes lactobacilli, bacteroides, enterobacilli, Proteus, and Pseudomonas. The lactobacilli and the bacteroides constitute the most important fraction of the cellular population, and the size of that bacterial population remains constant. In contrast, E, coli, Proteus, and Pseudomonas are much less abundant, and the... 

Intestinal bacteria contribute considerably toward fulfilling the vitamin requirements listed in Table XIX. This can be considered an example of symbiosis. Man s requirement of vitamin K, for example, is filled almost entirely by the bacteria. Cows which received no thiamine or riboflavin still produced milk with a normal content of vitamins. And on the other hand, high doses of sulfonamides or antibiotics can liquidate the intestinal flora to such an extent that the source of vitamins stops suddenly and serious avitaminoses may develop unless the diet is corrected. 

The symptoms of vitamin K deficiency are a tendency to bleed and disturbances in blood clotting. Of the many clotting factors (end of Chapt. IV-9), prothrombin is affected primarily it is produced in insufficient amounts in vitamin K deficiency. In man the deficiency symptoms are rather rare, because the intestinal flora produces enough of the vitamin to contribute materially in the supply. 

Although some of the available riboflavin in natural foods may be present as the free vitamin, ready for intestinal transport, a larger fraction is present in the form of phosphorylated coenzymes FMN and flavin adenine dinucleotide (FAD), and there may also be very small amoimts of a gluco-side of the vitamin. These forms are all efficiently converted to free vitamin by enzymes secreted into the gut lumen, and they are therefore highly available for absorption. There are also small amounts of covalently bound forms of riboflavin, present in enzymes such as succinate dehydrogenase (succinate ubiquinone oxidoreductase EC 1.3.5.1), which cannot be released by the hydrolytic enzymes in the gut and are therefore unavailable for absorption. Also unavailable (or very poorly available) in man is the riboflavin synthesized by the gut flora of the large bowel. Certain animal species such as rodents can utilize this riboflavin source by coprophagy. 

Fig. 7.4.2 The origin and metabolism of TMA in man. This figure shows the molecular defect in the flavin-containing mono-oxygenase ( ) in trimethylaminuria or fish odour syndrome. The dashed line indicates the minor metabolic pathway in healthy volunteers. Enzyme steps marked with B are in the intestinal bacterial flora. DMA Dimethylamine, MMA monomethyl-...

The microbiological activity in the distal parts of the intestine is much less than in man, which has implications for drugs or excipients that are metabolised by gut flora enzymes, or drug release principles, based on this process. 

Vitamin K may be synthesized by intestinal bacteria, and this explains why it is so diflScult to produce vitamin K deficiency by dietary restriction. It has never been produced in man by this means. A change in intestinal flora, such as may be produced by the use of sulfa drugs or antibiotics, often alters the amount of vitamin K avaUahle to the organism (Nutrition Foundation, 1953). 

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