Synthesis of B vitamins by intestinal

Vitamin B Refection.—Spontaneous recovery from avitaminosis Bj + Bg while on a deficiency diet has been observed, especially among rats, and is accompanied by a marked change in the bacterial flora of the intestine. It is due to local synthesis of the vitamins by micro-organisms in the lower alimentary tract, and is termed refection. It is favoured by a high starch content in the deficiency diet. Refection is very important, and may introduce a serious error into methods of biological assay. 

Increased absorption is almost certainly the cause of the raising of the blood and tissue levels of vitamin B12 by sorbitol and some other substances. Intestinal synthesis is responsible for the far more dramatic sparing of other B vitamins by sorbitol, ascorbic acid, and several other substances, so that animals become completely independent of dietary sources of these vitamins. Finally, the ability of ascorbic acid to prolong the life of animals deficient in folic acid is very probably due to the promotion of the synthesis of this vitamin in the tissues. 

The establishment of allowances for vitamin B-6 is complicated by the following facts (1) the requirement varies with dietary protein intake—there is increased need for vitamin B-6 with increased intakes of protein (2) the uncertainty of the availability of the vitamin in the diet and (3) the uncertainty as to the extent of intestinal bacterial synthesis of the vitamin, and the degree to which it is utilized by the body. Also, there is evidence of increased need of the vitamin in pregnancy and lactation, in the elderly, and in various pathologic and genetic disturbances. Nevertheless, the NRC has set recommended allowances to assure a safety margin and to make a deficiency unlikely under most circumstances. Discussion follows ... 

Bacterial action in the large intestine may have a beneficial effect owing to the synthesis of some of the B vitamins, which may be absorbed and utilised by the host. Synthesis of most of the vitamins in the digestive tract of the pig is, however, insufficient to meet the daily requirements and a dietary source is needed. 

A considerable amount of biotin is synthesized by human intestinal bacteria, as evidenced by the fact that 3 to 6 times more biotin is excreted in the urine and feces than is ingested. But synthesis in the gut may occur too late in the intestinal passage to be absorbed well and play much of a direct role as a biotin source. Also, several variables affect the microbial synthesis in the intestines, including the carbohydrate source of the diet (starch, glucose, sucrose, etc.), the presence of other B vitamins, and the presence or absence of antimicrobial drugs and antibiotics. 

The phenomenon of vitamin synthesis by bacteria presents important considerations in the nutrition of man. Its full significance, however, should await a more complete knowledge of the human need for the B vitamins than we now possess. At the present time, we are certain that at least part of our requirements are furnished by bacterial action in the intestines. It is, therefore, comforting to know that we can at least rely to some extent on this mechanism to supplement the average American diet should the ever persistent vitamin vendor fail in his benevolent task. 

Bile acids have two major functions in man (a) they form a catabolic pathway of cholesterol metabolism, and (b) they play an essential role in intestinal absorption of fat, cholesterol, and fat-soluble vitamins. These functions may be so vital that a genetic mutant with absence of bile acids, if at all developed, is obviously incapable of life, and therefore this type of inborn error of metabolism is not yet known clinically. A slightly decreased bile acid production, i.e., reduced cholesterol catabolism, as a primary phenomenon can lead to hypercholesterolemia without fat malabsorption, as has been suggested to be the case in familial hypercholesterolemia. A relative defect in bile salt production may lead to gallstone formation. A more severe defect in bile acid synthesis and biliary excretion found secondarily in liver disease causes fat malabsorption. This may be associated with hypercholesterolemia according to whether the bile salt deficiency is due to decreased function of parenchymal cells, as in liver cirrhosis, or whether the biliary excretory function is predominantly disturbed, as in biliary cirrhosis or extrahepatic biliary occlusion. Finally, an augmented cholesterol production in obesity is partially balanced by increased cholesterol catabolism via bile acids, while interruption of the enterohepatic circulation by ileal dysfunction or cholestyramine leads to intestinal bile salt deficiency despite an up to twentyfold increase in bile salt synthesis, to fat malabsorption, and to a fall in serum cholesterol. 

SOURCES OF VITAMIN B-12. The sole source of vitamin B-12 in nature is synthesis by microorganisms. It is synthesized by the many microorganisms in the rumen and intestine of herbivorous animals. The vitamin B-12 bound to a protein in animal foods results from such synthesis. This explains why vitamin B-12 is found in all foods of animal origin. 

Some vitamin B-12 is formed by microoiganisms in the intestinal tract of human beings. However, the synthesis is so far down in the colon that little of it may be absorbed. 

A completely independent study implicating the intestinal bacteria was that of Theiler and his associates (13) in ruminant animals. In the attempt to reproduce experimentally a South African paralytic disease known as lamzietke they fed cattle an experimental diet deficient in vitamin B and noted that evidences of deficiency failed to develop although pigeons on the same diet developed polyneuritis promptly. They assumed that either the vitamin requirement of cattle was extremely low or that it had been satisfied by bacterial synthesis in the intestinal tract the latter explanation seemed the more probable. 

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