Probably the pioneer in this study was Bouchard, who almost a quarter of a century ago enunciated the doctrine of auto-intoxication, declaring that, apart from the poisons swallowed in our foods, the alimentary canal was flooded with toxins which were products of the decomposition of food. Many of the end-products associated with the undigested particles of proteins, chiefly in the colon, are not really toxic, and comprise members of the fatty series, e.g., the amino-acids, leucin, alanin, aspartic acid, glutamic acid, butylalanin, glycocoll, the aromatic series, tyrosin, tryptophane, phenylalanin. But there are likewise present more decidedly toxic substances, partly derived from the disintegration of some of the foregoing, e.g., indol, skatol, cresol, leucomaines and ptomaines, such as putrescin (derived from arginin), cadaverin (the product of lysin), muscarin, neurin, and various poisonous gases.

He conjectured that bacteria had much to do in this production, but it was reserved for later workers to isolate and differentiate them. Inasmuch, however, as ethereal sulphates, indican, etc, were to be discovered in the urine, this was considered to be conclusive evidence that the toxins had gained an entrance into the circulation through the intestinal wall. As the alimentary canal of a newly-born child is perfectly free from microbes - which soon, however, obtain admission, and eventually swarm therein - it is easy to understand that as years roll on it develops into a condition far from aseptic.

Amongst others, Cohendy and Tissier have given much careful study to the intestinal bacteria, and they assert that although the number of the species is limited, quite two-thirds of the faeces is composed entirely of bacteria, chiefly of the anaerobic variety. Cohendy estimated that every milligram of faecal matter contained something like 150 million bacilli, of which, however, only about 3 per cent. were alive, although the others had lived for some time in the bowel. The character of these micro-organisms varies according to their position, but they may be roughly divided into two classes: (1) Saccharolytic, or amylolytic, organisms, which feed on starch, sugar, dextrin, and hydrocarbons generally. These produce acid substances such as lactic, acetic, succinic, butyric acids, which, although irritants and more or less harmful in character, are not deadly poisons, some of them appearing to exert a restraining influence on putrefaction. (2) Proteolytic micro-organisms which feed upon nitrogenous substances, these undergoing successive transformations until they produce toxins of putrefaction, highly offensive to smell and taste, and ranking among the most deadly poisons known. The saccharolytes are found principally in the small intestine, while the proteolytes almost entirely inhabit the colon.

Although there are other micro-organisms such as the peptolytes, which normally inhabit the intestinal canal, these may be considered as the two chief divisions, but in addition there may be others which may have obtained access accidentally, e.g., the comma and typhoid bacilli, the pneumo-coccus, etc. For the most part, however, these pathogenic organisms, which gain admission by the mouth, are destroyed by the gastric juice. The advantage of adopting this classification is that we can thus roughly divide the inhabitants of the intestine into two opposing categories, the one mainly harmful and the other harmless, if not indeed beneficial. This, in any case, is the claim made by Metchnikoff, and to demonstrate the active utility of many of these organisms he proved that chickens reared as far as possible without intestinal microbes languished and died, whereas others fed in the same way - though with a full supply of intestinal microbes - came to perfect development. His contention, therefore, is that bacteria are necessary to the completion of nutrition, so that what may be called a stupefying conflict is constantly being waged in the alimentary canal between the two classes of microbes, the proteolytes, which have a baneful effect on the system through their toxins, being inhibited - but not killed - by the saccharolytes, which have thus on the whole a salutary influence on the well-being of the individual. Now as proteolytes can only develop in an alkaline medium, and remain inert or inactive in an acid or even less alkaline medium, it will be seen that the colon is under ordinary circumstances entirely favourable to their development. He considers, therefore, that curdled milk, which is simply a pure culture of the most powerful lactic-acid-producing organism which is able to survive its passage through the stomach and go on producing its beneficial acid in a nascent condition in the colon, is an agency of the first order for improving the health and prolonging the life of the individual.

It has long been recognised that lactic acid has a beneficial therapeutic influence on intestinal ailments, Hayem having administered it by the mouth with this intent, and Herter by the bowel for the same purpose. In the former case its action was futile, as it was rapidly decomposed into carbonic acid and water; but in the latter instance its use was followed by a distinct diminution of the ethereal sulphates and indican in the urine. The employment of the acid per se is, however, much inferior to the use of a means for manufacturing it in situ, especially as it has been proved that the lactic acid bacillus acts in an automatic manner, its own growth being inhibited when the total acidity from its own product has been reduced by decomposition of the excess of the lactic acid. It is important to remember, however, that any salutary influence accruing is to be attributed to the lactic acid and not to the germs.

It is an unquestionable fact that many organisms capable of initiating intestinal putrefaction have been isolated, amongst them being the Bacillus imtreficus, which is spore-bearing, thrives in milk without causing it to coagulate, and digests the casein; the Bacillus Welcliii perfringens, or aerogenes; and the Bacillus sporogencs of Klein. These organisms manufacture toxins, which pass through porcelain filters, resist a temperature of 100° C, and can kill rabbits. Their action, moreover, is somewhat capricious, as Welch's bacillus taken from a case of appendicitis proved almost inactive, whereas other specimens taken from quite healthy individuals were sufficiently powerful to kill animals. Fortunately, the normal individual is richly provided with antitoxic organs in the liver, thyroid, adrenals, to say nothing of the mucous membrane of the bowel and the skin and kidneys, so that it is a rare occurrence for the average individual who obeys the laws of health, and particularly who lives on a well-balanced varied dietary, to be deleteriously affected by the toxins manufactured in his alimentary canal. But conditions may and do arise constantly, due to exposure to cold, exhaustion, and especially failure to recognise the advantages of a varied and correctly proportioned dietary, when the antitoxic organs may fail in their beneficent labours, or the toxins formed may be in excess of their antidotal powers, and thus disease in some form is likely to arise.

Metchnikoff has proved decisively the extreme sensitiveness of these bacteria to alterations in the diet, so much so that merely changing the particular brand of peptone is sufficient to produce a marked variation in the proportion of the microorganisms. He inoculated with faecal matter two culture tubes, one containing minced meat and water, and the other minced vegetable and water. In two days the toxins of the former tube were sufficiently powerful to kill rabbits, whereas the latter, on being injected, proved quite innocuous, and the germs contained in the two tubes were quite different in character.

Herter and Kendall have also by feeding experiments shown that the character of the intestinal flora is directly connected with the nature of the food. These were conducted on monkeys and cats, which were fed on exclusively protein and exclusively carbohydrate food, the transitions from the one to the other being effected rapidly. On a protein diet, proteolytic bacteria abounded, and on a carbohydrate diet these organisms were rapidly replaced by others of an acidophilic, non-proteo-lysing type. At the same time there was a reduction of the aromatic oxyacids and indican in the urine, and indol, skatol, phenol, and bound sulphuretted hydrogen of the faeces, and the animals improved in spirits and activity. It is quite evident that the change of diet involved the destruction of the previous bacterial flora, and the authors remark that in intestinal disease, "where undeniable bacteria abound, both on a protein diet and on a carbohydrate diet, frequent alterations in the chemical nature of the diet are beneficial by interfering with the establishment of any one type of bacteria in the intestine."

Metchnikoff long ago suggested that to aid the body in its effort to protect itself against the toxic products of putrefaction it was wise to eliminate from the diet such articles of food, e.g., meat, as conduce to intestinal fermentation, in favour of milk, which is much less liable to fermentative changes, and to reinforce the latter by the addition of the lactic acid bacillus. He declares that the poisonous excretions, which he indicates are paracresol and indol, being absorbed by the normal walls of the bowel, exercise in all cases a toxic irritant effect on the organism, producing an increase in the connective tissue of the organs and bloodvessels, thus setting up sclerosis, endarteritis, and finally senile decay.