senility and intestinal flora - tahoma clinic · orla-jensen (15 , 16) as early 1912 suggested the...

Senility and Intestinal FloraA Reexamination of Metchnikoffs Hypothesis

S. ORLA-JENSEN, ERIK OLSEN, AND TORBEN GEILL

I N ORDER TO INVESTIGATE THE DIFFERENCESWHICH MAY EXIST BETWEEN THE FLORA OFTHE FECES OF YOUNGER PERSONS IN THEIRPRIME AND THOSE OF OLD PEOPLE AND TODETERMINE WHETHER SUCH DIFFERENCESCDULD BE DEMONSTRATED BETWEEN THEFECES OF HEALTHY AND OF SENILE OLD PEO-PLE, DRS. ORLA-JENSEN, OLSEN, AND GEILLCONDUCTED EXPERIMENTS WITH THE OLDPEOPLE OF D E GAMLES B Y AND THE YOUNGLABORATORY WORKERS AT THE INSTITUTION.THEY CAME TO THE CONCLUSION THAT IT ISNOT THE UNDESIRABLE FLORA FOUND IN THEAGED WHICH CAUSES IMPAIRED DIGESTION,BUT RATHER THE IMPAIRED DIGESTIONWHICH CAUSES THE UNDESIRABLE INTES-TINAL FLORA.

"\yTODERN research in heredity has led to-̂ * the conclusion that the attainmentof old age is conditioned by heredity, andthe factor is fortunately dominant. Thus ifone parent reaches old age, the descendantsmay also reach it. But few persons live incircumstances so comfortable in all respectsthat they reach the maximum possible age!Life is in fact often shortened by disease,accident, worry of one kind or another,overwork, and even by irregular or immod-erate living. The most intensely vital peo-ple are particularly prone to the latter, andthus a leveling of age takes place. Never-theless, apparently weak people often sur-vive to old age. The Danish author, CarlEwald, relates a story of an old postmaster,who, on being asked how he managed tokeep so young, answered simply that fromhis youth he had always had a weak stomachand had been obliged to be very carefulabout eating and drinking.

There is no doubt that the prolongationof human life which has actually taken placein modern times is due to the improvementof hygiene, personal not less than public.But this prolongation of life is not as greatas the statistics show, because it dependsmainly on the decrease in the death rate ofbabies, which has nothing to do with theage of adults, although both are influenced—in very different degree—by milk hygiene.For bottle-fed children this is, of course, ofdecisive importance, but it is also of im-portance for adults, because, as we shallsee later, they also ought to consume milk.

In the seventies of the last century E.Baumann (1, 2, 3, 4, 5, 6) showed thatputrefaction, very much like the putrefac-tion of the proteins outside the organism,can also take place in the human colon. Bythis process ptomaines and noxious aromaticsubstances (skatole, indole, cresols, phenols)are formed. The latter are excreted in theurine combined mainly with sulphuric acid,so that the extent of the putrefactive proc-esses in the colon can be followed by anal-yses of the urine. Thus through this processa stream of pernicious substances flowsconstantly through the body and, therefore,a sensible mode of life is of importance. Forinstance, moderation in meat eating willlimit the formation and excretion of thesesubstances.

At the end of last century it was alreadyknown that putrefactive bacteria are sus-ceptible to acid and thus that putrefactiveprocesses can be suppressed by adding acidor sugar, which is turned into acid by fer-mentation. Use is made of the lactic acidfermentation to preserve vegetables (suchas silage and sauerkraut) and to prevent the

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ORLA-JENSEN, OLSEN, AND GEILL

Dr. Orla-Jensen received his Ph.D. degreefrom the University of Copenhagen in 1907,a D.Sc. from the University of Syracuse in1923 and another from Rutgers University in1930. He was professor of food and fermen-tation industries at the Royal Danish Tech-nical College, Copenhagen, from 1906 to1946. Dr. Orla-Jensen is a member of theRoyal Danish Academy of Sciences and ofthe Academy of Sciences in Washington andis now chairman of the Danish GerontologicalSociety.

Dr. Olsen received his M.Sc. in agriculturefrom the Royal Agricultural College, Copen-hagen, in 1934. He is a lecturer in microbi-ology at the Royal Technical College, Copen-hagen, and he is a member of the DanishGerontological Society.

Dr. Geill, after receiving his M.D. degreefrom the University of Copenhagen in 1914,continued his studies at Vienna and Paris.He has been chief physician of De GamlesBy since 1936. Dr. Geill is a member of theDanish Gerontological Society, and his chiefresearch subjects are gerontology, cardiology,and vitaminology.

putrefaction and ensure the ripening ofgreen cheese, which consists mainly of pro-teins. It was therefore quite natural thatthe Russian zoologist, Metchnikoff (11, 12),proposed at the beginning of this centuryto suppress putrefaction in the colon by in-oculating it with powerful lactic acidbacteria.

Metchnikoff thought that arteriosclerosis,causing senility and shortening the life ofman, was linked with putrefaction in thecolon. This^ thesis has never been proved ordisproved, but it is now known that arteri-osclerosis can arise from many causes otherthan poisoning from the colon, e.g., acuteinfectious diseases or metabolic diseasessuch as diabetes. Metchnikoff regarded thecolon as a noxious, sedimentary organ. Itsonly real function, like that of the urinarybladder, should be to ensure the excretionof residual products at convenient intervals.This arrangement, he thought, might be ofgreat importance to animals when they hadto run for hours to escape their pursuers,

but for mankind it was normally unneces-sary.

This opinion is, of course, quite wrong,because without a colon food could not beutilized as completely as it is; no significantbacterial activity normally proceeds in thestomach and the small intestine. As a ruleit takes two to three hours for the food topass through the winding small intestine,which is about 7 metres long, while it re-mains for twelve to twenty-four hours inthe colon, which is only 1 metre in length.Thus many rather indigestible substanceswhich enzymes are incapable of managingare brought into solution by bacteria, andfor the most part absorbed, together withthe large amount of water present in thecolon.

When entering the colon, the food resi-dues are highly diluted, and it is here thatthey assume the semi-solid form character-istic of normal feces. It is true that thepower of absorption of the colon is verysmall in comparison with that of the smallintestine, but on the other hand the delayin the colon is so long that the products offermentation, both nitrogenous and non-nitrogenous, the latter mainly ether-solublelactic acid, are in fact absorbed. Neverthe-less, some of the calorific value of the nutri-ents is lost in the fermentation processes.In a pure lactic acid fermentation only one-third is lost; in fermentation by the coli-form bacteria the loss is greater owing tothe evolution of gas. Physiologically it isof great importance that the lactic acidformed is dextro-rotatory and not laevo-rota-tory, since Parnas (20) has shown, as earlyas 1912, that the human organism is capableof utilizing only the former. Unfortunatelythe coliform bacteria of the colon mainlyform laevo-lactic acid.

Intestinal putrefaction is, of course, moremarked when evacuation is slow than whenit is normal. The resulting harmful effect is,however, counteracted because absorptionin the colon ceases almost entirely when thecontents are dry. The organism has alsoan alternative method of defending itself

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against poisoning. If putrefaction is active,much hydrogen sulphide is formed, and asthe sulphides are highly purgative rapidevacuation is ensured. The constipating ef-fect of iron and bismuth salts is dependenton the fact that they render the sulphideinsoluble.

When Metchnikoff learned that centen-arians were especially numerous in Bulgariaand that Yoghourt is the national food, hevery naturally suggested the inoculation ofthe intestine with this sour milk product.Metchnikoff, who was blessed more withintuition than with the patience of the truescientist, felt so sure about this that with-out further research he wrote two semi-pop-ular works on the subject. Both were trans-lated into many languages. One may stillread with interest his philosophic reflectionsabout how everything in this world wouldimprove if people could grow old withoutsuffering the infirmities of age. Among theexperienced and seasoned old men, full ofwisdom, it should not be difficult to findideal judges and politicians to guide and rulethe peoples.

Fortified by these theories it was quitenatural that Yoghourt should begin a tri-umphal march the world over. Not onlywas Yoghourt eaten as such, it was alsosold in tablets said to contain Yoghourtbacteria. As a rule they contained onlyspores of putrefactive bacteria, since Yog-hourt bacteria do not easily tolerate drying.Many physicians were firm believers inMetchnikofPs theories, and some went sofar as to remove larger or smaller parts ofthe colon from patients suffering from in-digestion.

As an excuse for Metchnikoff it can besaid that when he conceived his great the-ory the time was not yet ripe for proving it.Like the science of the taxonomy of plants,the taxonomy of bacteria rested at that timeon an essentially morphologic basis which,with bacteria, did not permit as accurate aclassification as that which has become pos-sible by the use of physiologic methods.Many errors arose from the assumption

that the bacteria excreted with the feceswere identical with those taken in with thefood, the only criterion being that theylooked alike under the microscope.

With regard to the lactic acid bacteria itis now known that widely different speciesexist and develop in different places. Vege-table substances, milk, saliva, and feces allcontain specific lactic acid bacteria. Fecesfrom herbivorous animals contain lactic acidbacteria entirely different from those foundin feces from carnivorous animals. Most ofthe lactic acid bacteria of milk cannot thriveat all in our intestinal canal. Hence in thefeces of people who daily consume sourmilk or Yoghourt one rarely finds lacticacid bacteria differing from those found inpeople who do not consume these products.

The predominant lactic acid bacteria inthe feces of healthy persons are the so-calledenterococci, two rod-shaped bacteria, Ther-mobacterium intestinale (formerly calledBacillus acidophilus), and the forked ana-erobic Bacterium bifidum which are foundin large numbers. The latter, which wasoriginally thought to be found only in thefeces of babies, is in fact present in largenumbers in the feces of adults and maysometimes constitute half of the bacterialpopulation. It is therefore not surprisingthat the vaginal secretion in women is in-fected with Bact. bifidum and that in turnthe child is infected from the moment ofbirth.

If it is desired to establish lactic acidbacteria in the intestine it is useless to useYoghourt bacteria. Only lactic acid bacterianatural to the intestine can be used. Orla-Jensen (15, 16) as early as 1912, suggestedthe use of Bact. bifidum, and Rettger (21)has introduced acidophilus milk in Americawith success and shown that it is effectivein certain disturbances of the digestion.

A condition for the establishment of lacticacid bacteria in the colon is that sugar beavailable. The ordinary sugars, however,are completely absorbed in the small intes-tine unless they are fed in such amountsthat diarrhoea results. Diastaso and Schiller

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(9, 10) were the first to point out that dex-trin and lactose are not absorbed in thesmall intestine. As they statedj this is be-cause of the lack of the appropriate hydro-lytic enzymes. Although infants possesslactase, this enzyme, as was found later, isnot present in the adult.

In addition to dextrin and lactose, plantsundoubtedly contain other carbohydrateswhich-are not absorbed in the small intes-tine and which may produce acid in thecolon. Inulin is an example, but since itoccurs only in the roots of Scorzonera, inJerusalem artichokes, and in a more or lessroasted form in coffee substitutes, it is ofno practical significance. But that dextrin(or the dextrins) behave as described is anobservation the full importance of which hasnever been sufficiently emphasized.

Dextrin is formed by the digestion ofstarch, and human beings consume starchto a greater extent than any other carbohy-drate. It would simply be impossible to eatcorresponding quantities of sugar withoutcausing diarrhoea. Since starch is hydro-lyzed in stages, it becomes a slowly availablesource of sugar. The sugar first formed isabsorbed before more appears and in thisway we avoid too large a sugar concentra-tion in the small intestine, while the dextrinwhich is formed ensures a certain degree ofacidity in the colon. This must explain whymany people who drink very little milknevertheless are in good health. What hasbeen said is especially true of consumers oflarge quantities of beer since they acquirelarge amounts of dextrin in that beverage.

To most people, however, milk is benefi-cial, not only because it is a general andeasily digestible food, but because in adultsthe milk sugar is not absorbed in the smallintestine but gets as far as the colon whereit is more easily fermented by the lactic acidbacteria present than are dextrin and inulin.Milk may therefore be replaced not only bypure milk sugar but by whey or whey-cheese.The latter contains, besides the water solu-ble vitamins of the milk, some 60 per centof milk sugar.

All investigators have found that milksugar may change the intestinal flora in theright direction. Thus Orla-Jensen and Win-ther (19), using a daily dose of 70 gm. ofmilk sugar (without inoculation), succeededin changing the intestinal flora in severalpersons to such a degree that the lactic acidbacteria—especially Bact. bifidum—predom-inated. The number of the coliform andputrefactive bacteria fell to a minimum (1per cent of the total amount of bacteria).If it is desired to establish lactic acid bac-teria, those organisms characteristic of theintestine must be used in the form of milkculture and not as tablets without milk.

In this way it is possible to cure certainintestinal diseases or disturbances of thedigestion. Whether it is possible in the sameway to prevent arteriosclerosis and senilityand thus to prolong human life is an entire-ly different matter, and the idea now findsno general acceptance. One thing should beremembered in this.connection, viz., that wehave passed from the one-sided bacteriologicage in which Metchnikoff lived to an exag-gerated vitamin and hormone age where,instead of sterilized food, uncooked foodis preferred. Those who still believe in thepossibility of prolonging life are of theopinion that the means must be the miracle-cure of vitamins and hormones. It is truethat the sex hormones, for a time at least,have proved rejuvenating.

Nevertheless nobody will deny the possi-bility of an association between the intestinalflora and senility according to Metchni-koff's idea. Shortly before the outbreakof the last war Or la-Jensen received a re-quest from Dr. Korenchevsky, Hon. Secre-tary of the British Society for Research onAgeing, to explore the idea. There is asimilar Society in Denmark and two of itsmembers, Dr. Torben Geill, Physician-in-Chief of De Gamles By (a Social Settlementfor the Aged in Copenhagen) and Dr. ErikOlsen, collaborated with Orla-Jensen in thepresent investigation. The present commu-nication represents a summary of this work,Senility and Intestinal Flora, which has beea

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published in detail with several tables inDei. Kongelige Danske Videnskab ernesSelskab Biologiske Skrijter (17).

As surgical procedures were out of thequestion in these investigations we had toconfine ourselves to the study of the intes-tinal bacteria found in freshly excreted feces.This, to be sure, only represents the lastpart of the intestine, but it is the most in-teresting for our purpose because it is herethat the putrefactive processes tend to takeplace.

The bacteria of the feces can be dividedinto three main groups: the lactic acid bacte-ria already mentioned, the coliform bacteria,and the putrefactive bacteria. The coliformbacteria occupy an intermediate place be-tween the two other groups, since in sugar-containing media they form acid and thus,like the lactic acid bacteria, prevent putre-faction, while in sugar-free media they formindole and other putrefactive products.Therefore, given the correct nutrimentsthe coliform bacteria are advantageous, al-though they deal less economically with thecarbohydrates than the lactic acid bacteria.Very possibly they are quite indispensablebecause they form K-vitamin (18).

The typical putrefactive bacteria are theones which ought especially to be suppressed.Under the anaerobic conditions of the colonClostridium welchii is the most numerous ofthese. As no putrefaction takes place incheese as long as the pH is maintained under5.6, it apparently should not be difficult toavoid putrefaction. Nevertheless in the rec-tum and also in the last part of the colonputrefaction can never be totally avoided.The pH of the feces is normally higher than6, often more than 7; and this is so eventhough large amounts of milk-sugar are in-gested. But of course, it is not unimportantif putrefaction sets in at the beginning ofthe colon or only at the end of it. Samplesof feces from the middle of the colon areonly to be obtained in conditions of diar-rhoea, and in such cases the pH can falleven to 5.5.

It has long been known that most of the

bacteria observed are dead. They originatehigher up in the digestive tract and perishin the lower sections where, however, newbacteria develop. Many of the dead micro-organisms are autolyzed and digested, where-by the nutrients they have consumed areagain utilized. As we know, these facts areof the greatest importance in ruminants. Inthis way it is made possible for them toutilize a small amount of ammonium saltsbecause in the rumen these are transformedto bacterial protein, which is later digested.

This phenomenon is also of importancefor the vitamin supply, since, in the diges-tive apparatus, vitamin-forming bacteriadevelop which when digested may make thesupply of particular vitamins unnecessary.For this reason cattle do not need to be sup-plied with vitamin B, and human adults maydo without vitamin K from extraneoussources.

Feces are extraordinarily rich in bacteria,which constitute 5 per cent of the volume.By direct counting under the microscopeabout 100,000,000,000 of bacteria per gramare normally found, of which some 5,000,-000,000 per gram are living. The numbersas well as' the species of the bacteria foundin feces vary greatly from day to day evenin the same person, the diet having a pro-found influence. After some preliminaryinvestigations we succeeded in finding twolactic acid bacteria which are characteristicfor certain persons: Bacterium bifidum andStreptococcus salivarius.

Bact. bifidum is always found in feces ofcertain persons and in considerable numberswhereas it seems lacking in the feces ofothers. We designate these persons as"bifidum-positive" and "bifidum-negative"respectively.

If milk cultures of Bact. bifidum aregiven to bifidum-negative persons for a pro-tracted period this organism will usuallythrive in their digestive canal, but it mayfail to establish itself and if established maydisappear completely if the administrationof the cultures is discontinued. The ordinarysalivary streptococcus, Str. salivarius, which

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has not been demonstrated in feces before,is often found in the feces of old persons.In one case we found 20 millions per gram,a number which remained remarkably con-stant over a period of three to four years.It is therefore natural that in our bacterio-logic investigations of feces we have beenespecially interested in these two indicator-bacteria. A detailed description of the meth-od of investigation, including the techniqueemployed for counting the bacteria in thestool, can be found in the original paper (17).

The direct approach to the solution of thepresent problem would be nutritional studieswith feces examination conducted on a largergroup of individuals throughout the greaterpart of their lives, but this is, of course,not possible. There was therefore no alter-native but to evaluate on a statistical basisany differences which may exist between theflora of the feces of younger persons in theirprime and of those of old people and todetermine whether any differences could bedemonstrated between the feces of healthyand senile old people. For the study of senileold people the inmates of De gamles By whoall live under very nearly the same condi-tions, constituted an unusually suitablegroup.

to the degree of general arteriosclerosis, butsuch a classification is impossible to makewith living persons. Gradually as the per-sons under observation died the degree ofarteriosclerosis was determined by autopsy.The postmortem findings have not so far in-validated the method of classification used.This is not surprising, since most of thesubjects of investigation had done manualwork. In people of that kind, arteriosclero-sis nearly always starts in the brain, butexperience has shown that in brain-workersit rarely begins in the brain, but in the re-gion of the heart (angina pectoris) or else-where.

In the following table the results are sum-marized.

From this table it is perfectly clear thatthe intestinal flora of the aged and especiallyof old senile people is less advantageous thanthat of younger people. On the one handthere are far less bifidum-positive personsamong the aged, and on the other there aremany more with putrefactive bacteria in theintestinal canal than among the young ones.

It may be objected that the number ofsubjects under observation was too smallor that our research methods were not ac-curate enough. But the differences are toogreat to be cancelled out by any likely er-

Persons under observation

Percentage of persons having in their feces (per gram) more than100,000,000

Str. salivarius1,000,000,000 I 100,000,000

Bact. bifidum100,000,000Clostridia

Young (30 to 40 years)Old, nonsenile (above 70 years)Old, senile (above 70 years)

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The younger persons were all laboratoryworkers 30 to 40 years of age. The olderpersons were all more than 70 years old andsome were over 80. There were 31 senileand 32 nonsenile persons almost equallydivided between men and women. Sincecalcification of the arteries does not alwaysstart in the brain, it would have been betterif the classification had been made according

rors of method, and, moreover, our resultswere confirmed by the following investiga-tions which show that it is not the undesir-able flora of the aged which causes theirimpaired digestion, but rather the impaireddigestion which causes the undesirable in-testinal flora.

Achlorhydria, or failing production ofhydrochloric acid in the stomach, is a typical

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SENILITY AND INTESTINAL FLORA 11

sign of old age, and it seemed natural to as-sociate the large number of Str. salivarius,which were frequently found*in the feces ofold people, with this phenomenon. An inves-tigation actually showed that persons inwhom Str. salivarius was a prominent in-habitant of the intestine suffered from ach-lorhydria. They were also bifidum-negative.

In the hydrochloric acid of the stomachnature has provided man and animals witha wonderful means of protection against thelarge numbers of bacteria in the food—bacteria which may be more or less harmfulif not actually pathogenic. In the dysenteryepidemic in Aarhus (Denmark) in 1943, itwas mainly the aged who suffered, and inthe repeated paradysentery epidemics inDe Gamles By only the old people becameill, the staff, on the same diet, not beingaffected.

It is undoubtedly a fact that the bacteriaof the saliva, which normally live in a neutralmedium, are rather sensitive to acid, forwhich reason they do not survive the passagethrough the stomach when acid productionis normal. We have pursued this questionfurther by studying the bacteria in the con-tents of the stomach after Ewald's test meal,both in subjects with normal production ofhydrochloric acid and in patients with ach-lorhydria. Since in the latter the contentsof the stomach are emptied quite rapidly,samples were obtained after twenty minutes.

Under these conditions the pH of the con-tents of the stomach was, in normal persons,usually less than 2, and only a few thousandsof bacteria were found per 1 cc. (which isless than in cow's milk obtained underhygienic conditions). If the samples ofgastric contents were left standing for threehours at blood temperature, the number ofbacteria fell to a few hundreds per 1 cc. ow-ing to the lethal action of the hydrochloricacid.

The situation is different regarding thecontents of the stomach of persons withachlorhydria, where the pH value is 5 orhigher. In these samples millions of bacteriaper 1 cc, mostly streptococci, e.g., Str. sal-

ivarius, were found, and if the samples wereleft standing for three hours at blood tem-perature they multiplied rapidly.

It follows, therefore, that the contents ofthe small intestine in normal persons arealmost free from bacteria, while in personswith achlorhydria the contents are heavilyinfected inter alia with lactic acid bacteria,which convert most of the nonabsorbablesugars already in the small intestine intoabsorbable lactic acid. Thus no sugarreaches the colon. Without sugar Bact.bifidum is unable to multiply and form acidin the colon; hence people with achlorhydriaare, as a rule, bifidum-negative.

Another still more serious aspect is theinadequate digestion of the proteins in theabsence of hydrochloric acid, not only inthe stomach, but in the duodenum, since itis the acid in the contents which, with theaid of the hormone secretion, causes theflow of the pancreatic juice.

Further, since old people do not chewtheir food properly, all conditions are pres-ent for active putrefactive processes in thecolon, viz., insufficient formation of acid to-gether with considerable undigested protein.Such patients often suffer from evil-smellingdiarrhoea. Now we understand fully why,as a rule, in the feces of the aged fewerBact. bifidum and more putrefactive bac-teria are found than in younger, healthierpeople.

Nevertheless it seems strange that manypeople with achlorhydria apparently sufferno ill effect from the absence of hydrochloricacid; others, however, are subject to per-nicious anaemia. As Castle (8) demon-strated in 1929, the anti-pernicious anaemiafactor is formed in the stomach from a ther-molabile component (probably a hormone)and a thermostable component which orig-inates in the digestion of proteins and isdeposited in the liver. Therefore, the in-complete digestion of the proteins by per-sons with achlorhydria may account for thelack of the anti-pernicious anaemia factor,but in many cases the production of thehormone may also be impaired. According

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to Munk-Plum (14) the thermostable con-stituent may be tyrosine, and according toMeulengr'acht (13) the thermolabile sub-stance is formed in the pyloric section ofthe gastric mucous membrane. If this shouldbe the site of inflammation the formation ofthe anti-pernicious anaemia factor may beprevented. In pernicious anaemia we havefound, in two cases, an inflammation of themucous membrane of the stomach so severethat the test meal returned as a thick slimeand contained in both instances large num-bers of Staphylococcus aureus. In one casea pure culture of this organism (45 millionsper cc. of slime) was found.

In contrast to the enterococci, Bact. bifi-dum does not grow without sugar and acidformation, and it is therefore to be assumedthat in persons whose feces contain largenumbers of Bact. bifidum in the living state(as is usually the case when acid produc-tion of the stomach is normal) the contentsof the colon will always be acid enough tocheck putrefaction. With a reasonable diet,one containing not too much meat, but witha sufficiency of dextrin-forming foods, andmilk-sugar, e.g., bread and potatoes, andmilk foods supplemented by the necessaryvitamins, such persons will rarely sufferfrom excessive putrefactive processes in thecolon. But the danger is increased as soonas hydrochloric acid production fails, andMetchnikoff's theory of the prolongation oflife by means of the diet rests thus on theavoidance of achlorhydria or its harmfulconsequences.

It is known that the hydrochloric acid ofthe stomach is formed by certain cells inthe upper part of the fundus. The acid isformed from sodium chloride by a biochem-ical process of which at present we knownothing at all. In healthy persons the acidis formed in large amounts, about 1.5 L. ofO.ln hydrochloric acid daily. That is equalto 5.5 gm. of HC1. The liberated sodiumresidues are converted into carbonate orsalts of organic acid which pass into thebile or the pancreatic juice and partly neu-tralize the contents of the stomach as they

reach the duodeum. In this way the acidbase equilibrium of the organism remainsundisturbed. •

But such a disturbance is inevitable if onesupplies persons suffering from achlorhydriawith as much hydrochloric acid as is requiredto give pepsin (which as a rule they do notlack) its full activity. It is therefore en-tirely out of the question to supply thesepatients with hydrochloric acid in suchquantities. The problem is whether any-thing can be gained by- the ingestion of.smaller quantities of hydrochloric acid, andon this point opinions are divided. Manystomach specialists claim to have observedan improvement in their patients by givingthem only 1/20 to 1/40 of the amount ofhydrochloric acid produced in normal in-dividuals, and some of them even think thatsmall quantities of hydrochloric acid acti-vate normal hydrochloric acid production inthe stomach. This can hardly be the casein old patients suffering from achlorhydriain whom the glands of the fundus are totallyatrophied.

It was natural for us to try to contributeto the solution of this question by bacteri-ologic means. We did this by investigatingthe feces of individuals with achlorhydriawithin our personal acquaintance who hadfor some time been taking hydrochloric acidin small quantities at their chief meals andby investigating their feces before and afterthey had taken varying quantities of hydro-chloric acid. The hydrochloric acid wassupplied in the form of betain-hydrochloridetablets. Each tablet releases 0.06 gm. ofHC1. Thus with two tablets daily 0.12 gm.of HC1 is released or 0.24 gm. with fourtablets.

The latter quantity may easily disturb theacid-base equilibrium of the organism, caus-ing a calcium deficiency in the blood. Thiswas in fact the case with one woman, butthe deficiency passed quickly when she re-ceived tablets of calcium lactate in themornings. The patient has now followedthis cure for a couple of years anrd while itis true that it has not improved her achlor-

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hydria (the pH of the test meal was 7), hergeneral condition is essentially better, hercolon functions normally, and noxious diar-rhoea has ceased. Even though her fecesstill contain a large number of clostridia, 20per cent of the flora consists of Bact. bifi-dum and Str. salivarius is absent.

This case has taught us not to give ourpatients betain-hydrochloride at main mealswithout prescribing calcium lactate tabletsin the morning. At first we planned to givetwo tablets of betain-hydrochloride daily forthree weeks followed by double the quan-tity for another three weeks. Our investi-gations are by no means complete, but wealready have had encouraging results, ofwhich the following are examples.

The test meal withdrawn from two oldmen from De Gamles By showed pH valuesof 6.4 and 6.7 respectively. They both hadnumerous streptococci in the contents of thestomach and in the feces and both were bifi-dum-negative. The cure did not alter thenumbers of streptococci, but after takingtwo betain-hydrochloride tablets daily forsome time, they became bifidum-positive.One of these patients was also sufferingfrom pernicious anaemia. When the treat-ment was discontinued both became bifidum-negative again.

No good result, however, can be expectedwithout a reasonable diet containing souredmilk and some extra milk sugar. Even withsuch a diet it is not always possible to es-tablish Bact. bifidum in the intestinal canal.We have not yet had the opportunity ofobserving whether under such conditions itcan be established by adding milk culturesof the organism to the diet.

Organic acids are often used instead ofhydrochloric acid in the treatment of achlor-hydria. This medication has the advantageof not disturbing the acid-base equilibrium.In this connection it may be mentioned thatin the feces of a man 66 years old who hadfor thirteen years taken 3.5 gm. of citric aciddaily for his so-called achlorhydria, we foundno less than. 4,000,000,000 Bact. bifidumper gram of feces. We also found Str. sali-

varius, but further examination proved thathe was suffering only from hypochlorhydria,the pH in the test meal being 3.3. It ischaracteristic of the feces from patientswith hypochlorhydria (and usually also forpatients with achlorhydria, who receivehydrochloric acid) that both Bact. bifidumand Str. salivarius are present.

It seems from these investigations thatrelatively small amounts of acid taken atthe chief meals have a beneficial effect onthe flora of the colon in achlorhydria. Thesesmall amounts of acid are obviously capableof checking propagation of bacteria in thestomach and in the small intestine so thatsufficient sugar reaches the colon to permitBact. bifidum to grow.

It is possible that similar results can beachieved by eating plenty of acid fruits(including pickled cucumber) with mealsand drinking acid drinks like wine or sourmilk products. Milk in any form is bene-ficial owing to its content of milk sugar, butsour milk is more easily digested than sweetmilk, and this is especially true of peoplewith achlorhydria. Since Yoghourt is oneof the most acid of sour milk products,Metchnikoff may have been justified tosome extent in recommending it, but forreasons other than those he gave, becausethe bacteria contained in milk products donot thrive well in the human colon. Becauseof the great buffer action of the milk, how-ever, one can hardly recommend sour milkproducts as a source of acid for patientswith achlorhydria; hydrochloric and citricacid are more suited for the purpose. Butmilk products are of much benefit as asource of milk sugar and as a vehicle forbacteria. For the last purpose cultures ofBact. bifidum or of Tbm. intestinale aremost suitable. They are not to be taken atthe chief meals of the day but on an emptystomach together with calcium lactate tab-lets, if the latter are used.

That sour milk products also possess goodproperties other than those mentioned in theforegoing is apparent from the fact that,according to Brun and Nielsen (7), they

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favorably influence hyperchromic anaemiawhich, in contrast to pernicious anaemia, isnot accompanied nor caused by achlorhy-dria and is not cured by liver preparations.

SUMMARY1. Since Yoghourt bacteria grow but poor-

ly in the animal and human colon, they arenot suited for the purpose of suppressingthe putrefactive processes arising in thecolon.

2. Yoghourt can, however, like other sourmilk products, be of benefit, owing to itscontents of milk sugar and lactic acid.

3. If the colon in certain diseases is inneed of a change of its bacterial flora, thischange should be produced by means ofmilk cultures of the lactic acid bacteriacharacteristic of the normal colon, viz.,Bact. bifidum and Tbm. intestinale.

4. Normally these bacteria (especiallythe former) are present in ample amountsin the human colon. If they do not developand form acid it is because insufficient sugaris provided with the food.

5. The only sugars ordinarily occurringin the food which are not absorbed in thesmall intestine and thus reach the colon aredextrin and milk sugar. Hence it is impor-tant that the food contain ample amountsof dextrin or dextrin-forming substances,like starch and milk-sugar-containing sub-stances like milk.

6. Moreover, in order to avoid putrefac-tion in the colon, the food must not be toorich in protein. However, the proteins inmilk do not putrefy as easily as those inmeat (including meat or fish).

7. Some putrefaction in the last part ofthe colon and in the rectum cannot beavoided, but with a sensible diet there isextremely slight danger of the putrefactiveprocesses in the colon gaining the upperhand, so long as the hydrochloric acid pro-duction of the stomach is at its full height.

8. This arrangement by which most ofthe harmful bacteria in the food are destroyedis frequently apt to fail with advancing age.For this reason, feces from old people showson the average more putrefactive bacteria

and less Bact. bifidum than feces fromyoung and healthy people. When the acidproduction fails, there is also a greaterchance for the salivary streptococci, Str.salivarius, to pass unscathed through thestomach. If individuals are classified accord-ing to the strength of their hydrochloricacid production, the flora of their colon (orfeces) may be characterized as follows:

Persons with pH in a test meal lying be-tween 1.6 and 2 have normochlorhydria andnumerous Bact. bifidum in feces.

Persons with pH in a test meal lying be-tween 2 and 5 have hypochlorhydria and alarge number of both Bact. bifidum and Str.salivarius in feces.

Persons with pH in a test meal lying be-tween 5 and 7 have achlorhydria and alarge number of Str. salivarius in feces.

9. The reason that the putrefactive proc-esses in the colon increase when the hydro-chloric acid production in the stomach di-minishes is not only to be found in thepoorer digestion of the proteins, but also inthe circumstances that the food, instead ofbeing almost sterile when it leaves the stom-ach, is so filled with bacteria that the sugarfrom which acid is normally produced inthe colon already is fermented in the smallintestine.

10. The last mentioned condition seemsto be improved if only a little hydrochloricacid or citric acid is consumed at the chiefmeals. At the same time, in the morning,one should take about l/2 liter of some sourmilk product (buttermilk, sour milk, orYoghourt), preferably with the addition ofa little extra milk sugar. In certain cases,milk cultures of Tbm. intestinale or Bact.bifidum are to be preferred.

REFERENCES

1. Baumann, E.: Ueber Sulfosauren im Ham,Ber. d. deutsch. chem. Gesettsch. 9: S4-58,1876.

2. Baumann, E.: Ueber die Bildung vo& Phe&olbei der Faulniss von Eiweisskorpern. Ber. d,deutsch. chem. Gesellsch., 10: 685-686, 1877.

3. Baumann, E.: Ueber die Aetherschwefelsteender Phenole. Ztschr. f. physiol. Chem., 2:335-349, 1878-1879.

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4. Baumann, E.: Ueber die Entstehung des Phe-nols im Thierkorper und bei der Faulniss.Ztschr. f. physiol. Chem., 3: 250-253, 1879.

5. Baumann, E.: Weitere Beitrage zur Kenntnissder aromatischen Substanzen des Thierkorpers.Ztschr. f. physiol. Chem., 4: 304-322, 1880.

6. Baumann, E.: Die aromatischen Verbindungenim Ham und die Darmfaulniss. Ztschr. f.physiol. Chem., 10: 123-133, 1886.

7. Brun, G. C , and Nielsen, E.: Three Cases ofLiver Resistant Hyperchromic Anemia Treatedwith Preparations of Lactic Acid Bacteria.Ugesk. f. lager, 99: 483-489; 1937.

S. Castle, W. B.: Observations on the EtiologicalRelationship of Achylia Gastrica to PerniciousAnemia. I. The Effect of the Administrationto Patients with Pernicious Anemia of theContents of the Normal Human Stomach Re-covered after the Ingestion of Beef Muscle. Am,J. M. Sc, 178: 748-764, 1929.

9. Diastaso, A., and Schiller, J.: Sur la Trans-formation de la Flore Intestinale. Compt. rend.Soc. de biol., 66: 179-180, 1914.

10. Diastaso, A., and Schiller, J.: Sur PAcclima-tion dans le Gros Intestin de Microbes Etrang-ers a la Flore Intestinale. Compt. rend. Soc.de biol, 66: 234-244, 1914.

11. Metchnikoff, E.: Etude sur la Nature Humaine.Mason & Cie, Paris, 1903.

12. Metchnikoff, E.: Essais Optimistes, Englishtranslation edited by Chalmers Mitchell. W.Heineman, London, 1917.

13. Meulengracht, E.: Continued Investigations onthe Presence of the Antianemic Factor in Prep-arations of Dried Stomach Substance from theCardia, Fundus and Pylorus Regions. Adamed. Scandinav., 85: 50-88, 1935.

14. Munk-Plum., C.: Unders0gelser over Reticu-locytmodningen in Vitro. Nyt Nordisk Forlag,Copenhagen, 1944.

15. Orla-Jensen, S.: The Lactic Acid Bacteria.Copenhagen, 1919.

16. Orla-Jensen, S.: True Lactic Acid Bacteria.Kgl. Danske Videnskab. Selskab. Biol. Skrifter,2: 1-145, 1943.

17. Orla-Jensen, S., Olsen, E., and Geill, T.: Sen-ility and Intestinal Flora. Kgl. Danske Viden-skab.'Selskab. Biol. Skrifter, 3: 1-38, 1945.

18. Orla-Jensen, S., Orla-Jensen, A. D., Dam, H.,and Glavind, J.: "Dber K-vitaminbildung eini-ger Darmbakterien. Zentralbl. f. Bakt., 104:202-204, 1941.

19. Orla-Jensen, S., and Winther, 0.: Modifica-tion of Intestinal Flora in Rats and Men byMeans of Acidophilus Milk. Ugesk. j . lager,96: 913-916, 1934.

20. Parnas, K.: Ober das Schicksal der stereoisom-eren Milchsaure im Organismus des normalen

' Kaninchens. Biochem. Ztschr., 38: 53-64,1912.

21. Rettger, L. F.: Lactobacillus Acidophilus andits Therapeutic Application. Yale UniversityPress, New Haven, 1935.

Submitted for publication April 9, 1948The senior author's address is:

DR. S. ORLA-JENSENKASTELSVEJ, 1

COPENHAGEN, DENMARK

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senility and intestinal flora - tahoma clinic · orla-jensen (15 , 16) as early 1912 suggested the...

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