Adams

Baker

Booth

Donaldson

Drexler

French

Gilbert Hermann

Goldstein

H. Kent Axtell

Halsted

Jacobson

Krevans

Reilly

Reisher

Rubin

Schiffer

Scudamore

Seyderhelm

Sheehy

Siurala

Thomas E. Starzl

Tonnis

Toon

Ungley

Watson

English

PubMed

Hermann, G

Axtell, HK

Starzl, TE

Name not available

Bacterial contamination of the jejunum and vitamin B12 absorption

Crossref

Bacterial Contamination of the Jejunum and Vitamin B12 Absorption

HERMANN, G

AXTELL, HK

STARZL, TE

D-Scholarship@Pitt

Reprinted fro111 (J.LSTROEKTEROLOCY Val. 47, Nu. 1 July,  1964 Copyright a 1964 b?; The Willia~ns & Wilkins Co. Printed in 7'.S.A. BACTERIAL CONTAMINATION OF THE JEJUNUM AND VITAMIN BI2 AB- SORPTION GII,BERT HERMANN, M.D., H. KENT AXTELL, M.D., AND THOMAS E.STARZL, M.D. Department of Szc?.gery, Unizlersity of Colorado School of Medicine,  and the Sz~rgical  Laboratories of the Denver Veterans Adrrrz'nistration Hospital ,  Denver, Colorado 11acrccytic anemia due to stasis of the ble histologic changes suggestive of a msI- contents of the small intestine is a well absorptive defect. known clinical entity. I t  has been reported in association with improperly drained in- Materials and Method testinal segments a t  all levels of the small Healthy, dewormed mongrel dogs were bowel, including partially obstructed a f -  ~ s e d .  During the study, the animals were fererit loops after g a ~ t r e c t o m y , ~  multiple fed 1 can of Pard daily to which 100 gm. of jcJunal d iver t i cu la ,1 -bnd  with poorly lard mas added. This high fat diet was given draining ileal  segment^.^, as part of a study which will be reported There is nolv strong evidence tllat bat- separately. All animals handled the diet trrial ~\~crgro\vtll  in such intestinal seg- well and none developed steatorrhea by ac- merit$ plays a major role in the etiology of tual stool f a t  measurement. On the eighth tile hematologic 4-T At present, of this diet, each animal was fed a cap- however, the exact mechanism by which sule containing 0.67 pg. of vitamin B12 this bacterial proliferation leads to a mal- tagged with radioactive cobalt 57. The ra- absorption or nialutilization of vitamin BIZ dioactivity of these capsules had been pre- is still not clear. I n  an effort to throw fur- v iou~ly  measured in a large crystal scin- ther light on this matter, segments of jeju- tillation counter. After ingestion of the nun1 were interposed into the colon. We capsule, a total st001 collection was carried hoped by this technique to provide some in- out Over the next 72 hours while the animal forlnntion on two separate but related as- Was maintained on the same diet. The radio- pccts the relationship of bacterial pro- activity of the total stool sample was then liferation to nlalabsorptio~. First, because measured. Collections over a longer period the segment of small intestine subjected to of time failed to yield a significantly in- cont inuo~~s fecal would be creased amount of tracer material. The out of the upper alimentary stream, any de- amount of vitamin BIZ excreted was then fect in absorption of vitamin B1, could then calculated as a percentage of that given. be considered to occur as a result of a cir- Ten unoperated animals were used as culating substance such as a toxin. Second, controls. Three :tnimals had a 30 cm. seg- i t  could be observed whether prolonged bat- ment of upper jejunum interposed into the terial contamination of the mucosa of the colon, and 3 animals had a 60 cm. segment upper intestinal tract could cause recogniea- interposed. The isolated segment on its mesentery was interposed isoperistaltically Received December 13, 1963. Accepted March in an end-to-entj fashion with a standard 27, 1964. 2-layer technique (fig. 1). After recovering Address requests for reprints to: Dr. G. Her- mann, Veterans Administration Hospital, 1055 from surgery, the animals were sent to the Clermont Street, Denver, Colorado 80220. animal farm for 3 to  4 months. Upon return The work reported upon in tllis paper was sup- to  the laboratory, similar metabolic studies ported in part by United States Public Health were again carried out. The animals were Service, Grant A-6283, United States Public Health reexplored and biopsy specimens were taken Service, Washington, D .  C. from the transplanted segment. 61 62 H E R M A S S  E?' A I,. Vo l .  47,  'Vo. 1 Results terposition, both prc- arid l)obtopcrative HI, the 10 control animals, average B~~ excretions wcre all witl~in tlie noriiial range. excretion in the stool collection was 28 per The animals with 60 cm. interpositions llatl cent (S.D., 7.6) of the ingested dose. This is '1- similar to the figures of 33 per cent8 and At  reexploration, tile intcr~obcd loollb 10 to 47 cent"xcretion rept,rted in nor- were filled with fecal contents as expected. 11ial humans. Histologic study of the contanlinnted leju- group 1, those animals witll 30 cm. in- num failed to reveal any consistent or marked change in the Iiistologic pattern cf the jejunal niucosa. FIG. I. Segment of jejunum on ~ t s  mesentery ~nterposed into colon. TABLE 1 Fecal excretion of a test dose of cobalt labeled 11itarnin 1 3 1 2  zn zniact dogs and in dogs wzth ileal segrnents intrrposcd in t h ~  colon i 1 1 I Vitamin BIZ in stool 1 No. of ( dogs Control Group 1 F-I I F-15 F-1S Group 2 F-3:3 F-31 F-37 Length of interposed loop .- m. I 1 30 I 1 60 I Discussion Dose ad- ministered The anerriia associated wit11 stasis in the Dose ad- ministered upper intestin11 tract was inrestig'ited 1)y Seyderhelm1° in 1924. He  protluced partial obstruction by suturing a band of the all- donlinal wall fascia around tlie terininal ileum, and uostulated that the anemia t l i u ~  I produced was due to autointoxication from the chronically distended bowel. Several years later, Tonnis4 suggebted that  over- preopera- tively -- growth of bacteria in the clironically ob- structed loop might be important as a cause of the  anemia. More recently, Toon and \ITangc~ristc.eni and Watson and Witts," by using rats witlm surgically created blind loops as the experi- mental animal, mTere able to offer strong evidence that bacteria1 overgro~vth in the postopera- tively -- loops was intimateIy associated with tIlc en- suing macrocytic anernia. There has kwen no lack of clinical support for this concept. The reports of G ~ l d s t e i n , ~  Scudaniorc," and % ,4dams1 are particularly important, because. in their cases, there is no possibility of the alimentary stream bypassing a significant portion of the terminal ileurn which is now known to he the primary site of vitamin B,, absorption.12 The exact mechanism hy which bacterial overgrowth may interfere with the absorp- tion or utilization of vitamin El, is not clear. One theory holds that  there is bac- terial competition for the available vitamin B12. A second popular theory and one that is under investigation here is that a bacterial toxin is elaborated in and absorbed frorvl tlie blind intestinal l ~ o p . ~ V r c s u m a b I y ,  such a toxin niight act to block BI2  nictabolis~n within the hematopoetic tissues.l4% Clini- cal data,  howevcr, support the concept that Jrlly 1964 MACROCYII 'IC .4 IVEMIA tlic block is a t  tlie absorptive rather than Summary the utilization level. Because of this, i t  lias heen suggestedl0 that a circulating toxin ~ i iay  somellow interfere wit11 the ability of the n~ucosal surface of the ileurn to properly :~bsorb vitamin L312. Bccause i t  is known tlint tlic I):~cterial flora of the stagnant loop 15 siiililar to that of the colon,", 11+ li i t  was Iiol)c'ci tlint interposing a segnlent of jeju- null1 into tlie colon would demonstrate \\.lietlier I~acterial overgrowth in such a length of sinall intestine alone could inter- fcre with the absorption of vitamin U12. If this occurred, it would have to be by illcans of w circulating toxin because the remainder of the sillall intestine was not exposed to any An attempt was made to see if continu- ous massive bacterial contamination of the upper jejunum would adversely affect the absorption of vitamin BIZ or cause recog- nizable mucosal histologic changes, or both. This was done by interposing jejunal seg- ments into the colon for periods of up to 4 months. Vitamin BIZ uptake by the fecal excretion method bzfore and after this op- eration was measured. No effect on vitamin B12 absorption was evident. There was, in addition, no apparent effect on jejunal mor- phology of the interposed segment grossly or microscopically. ~l) i l lo~.er  of bacteria from the contaminated 1001,. I t  is cvitlcnt fro111 the results of this study that  if :I toxin is elaborated, i t  is not pro- flucseti k)p organi,inls normally present in the colon 11ntlt.r tlie conditio-1s of this experi- nicnt. A41tl~o~~gli  there are recognizable histologic c11-ngrs present in iiiany of the mrtlabsorp- tive states,ls. l9 the role that bacteria play, i f  any, in these morphologic changes is still nct certain. Some autllors have felt that :..ntihiotic~, by virtue of altering tlie in- trstinal fiora, were lielpful in tropical ~ p r u c . ~ ~  Others liavc not been able to repro- duce tlic snnle results in such a striking fasliion."~ " With the administration of neoinycin, Jacobson e t  n l . 2 ~ r o d u c e d  a lnalnbsorptivc syndron~e associated with cliangcs in jejunal morphology suggestive of early spruc. The relationship of their findings to changes in intestinal flora is un- certain, ho\vever. Nore recently, S ~ h i f f e r ~ ~  rc1)orted a case of "blind loop syndrome" :tb>ociated with inultiple diverticulitis of tlie jejunum in which peroral biopsy showed findings resembling thosc of early tropical spruc and celiac tliscasc. Tkius, tliere is apparently a t  this time no clcar cut agreement on whether changes in bacterial flora alone can lead to abnormali- ties in mucosal morphology. Alultiple sec- tions of jejunuln fro111 each animal in this study failed to reveal any abnorrilality even tl~ough they hacl been under continuous fe- cal containination for upwards of 4 months. ' REFERENCES 1. ADAMS, J. F. Postgastrectomy megaloblastic anemia and the loop syndrome. Gastroen- terologia, 89: 326, 1958. 2. GOLDSTEIN, F., WIRTS, C. W., AND KRAMER, S. The relationship of afferent limb stasis and bacterial flora to the production of postpastrectomy steatorrhea. Gastroenter- ology, 40: 47, 1961. 3. SCUDAMORE, H. H., HAGENDORN, A. B., WOLLAEGOR, E. E., AND OWEN, C. A. L)i- verticulosis of the small intestine and macro- cytic anemia with report of two cases and studies on absorption of radioactive vita- min B12. Gastroenterology, 34: 66, 1958. 4. SIURALA, M., AND KAIPAINEN, W. J. Intes- tinal megaloblastic anemia, treated with aureomycin and terramycin. Acta Med. Scand., 147: 197, 1953. 5. HALSTED, J. A., IAEWIS, P. M., A N D  GASSTER. M. A. Absorption of radioactive Vitamin B12 in the syndrome of megaloblastic anemia associated with intestinal stricture or anastomosis. Amer. J. Med., 20: 42, 1956. 6. DONALDSON, R. M., JR, hlalabsorption of CoGQ- labeled cyanocobalamin in rats with in- testinal diverticula. I. Evaluation of possi- ble mechanisms. Gastroenterology, 43: 271, 1962. 7 .  TOON,  R. W., AND WANOENPTEEN, 0. H. Anemia associated with blind intestinal seg- ments and its prevention with aureomycin. Proc. Soc. Exp. Biol. Med., 75: 762, 1950. 8. HALSTED, J. A,, LEWIS, P. M., HYOI~BOLL, E. E., GASSTER, M. A,, AND SWENDSEID, M. E. An evaluation of the fecal recovery method for determining intestinal absorp- tion of ~obalt6~-labeled vitamin B I Z  . J. Lab. Clin. Med., 48: 92, 1956. 64 HBIZMA :VN E?' .4 1,. V o l .  47, N o .  I 9. KREVANS, J .  R., CONLIY, C. L., A N D  SACHR. M. Influence of certain diseases on the ab- sorption of vitamin Blr from the gastroin- testinal tract. d. Clin. Invest., 33: 049, 1954. 10. SEYDERIIELM, It., LEHMAN, W., AND WICHEI~S. P. Experimental intestinal pernicious ane- mia of dogs. Klin. Wschr., 3: 1439, 1924. 11. WATSON, G. M., AND WITTS, L. J. Intestinal macrocytic anemia. Brit. Med. J., 1: 13, 1952. 12. BOOTH, C. C., AND MOLLIN, D. L. The site of absorption of vitamin B19 in man. Lancet, I :  18, 1959. 13. REILLY, R. W., AND KIRSNER, J .  B. The blind loop syndrome. Gastroenterology, 37: 421, 1959. 14. DREXLER, J. Effect of indole compounds on vitamin B I ~  utilization. Blood, 13: 239, 1958. 15. UNGLEY, C. C. Megaloblastic anemia following operations on intestine. Gastroenterologia, 79: 338, 1953. 16. T ~ N N I S ,  W., AND BRUSSIS, A. Changes of morphological blood picture in acute and chronic intestinal obstruction. Deutsch. Z. Chir., 233: 133, 1931. 17. DONALDSON, R. M., JR., CORRIGAN, H., AND NATSIOS, G. Malabsorption of Co60-labeled cyanocobalamin in rats with intestinal diverticula. 11. Studies on contents of the diverticula. Gastroenterology, 43: 282, 1962. 18. BAKER, S. J., IQNATIUS, M., MATHAN, V. I., VAISH, S. K., AND CHACKO, C. C. In Intestznul B i o p s y .  C i b a  Founda t ion  Study Group  A'o. 14, p. 84. Little, Brown & Company, Bos- ton, 1962. 19. RUBIN, C. E., BRASUBORG, L. L., PHELPS. P. C. A N D  TAYLOR, H. C.: Studies of celiac disease. I. The apparent identical and spe- cific nature of the duodenal and proxirnal jejunal lesion in celiac disease and idio- pathic sprue. Gastroenterology, 38: 28, 1960. 20. FRENCH, J. M., GADDIE, R., A N D  SMITH, N .  hI. Tropical sprue; a study of 7 cases and their response to  combined chemotherapy. Quart. J .  Med., 25: 333, 1956. 21. SHEEHY, T.  W., AND PEREZ-SANTIAGO. EAntibiotic therapy in tropical sprue. Gas- troenterology, 41: 208, 1961. 22. REISHER, K.  H., ROSEKBLUM, C., AND MOR- GAN, M. C. Urinary excretion of orally ad- ministered Co60 labeled vitamin Blr in nor- mal subjects and patients with pernicious anemia and sprue. Clin. Res. Proc., 2: 56, 1954. 23. JACOBSON, E .  D., PRIOR, J. T., AND FALOON, W. W. Malabsorptive syndrome induced by neomycin:morphologic alterations in the jejunal mucosa. J. Lab. Clin. Med., 56: 245, 1960. 24. SCHIFFER, L. M., FALOON, W. W., CHODOS, R. B., AND LOZNER, E. L. Malabsorptive syndrome associated with intestinal di- verticulosis. Gastroenterology, 42: 63, 1962. 

BACTERIAL CONTAMINATION OF THE JEJUNUM AND VITAMIN B12 ABSORPTION

http://d-scholarship.pitt.edu/3472/1/31735062123926.pdf

BACTERIAL CONTAMINATION OF THE JEJUNUM AND VITAMIN B12 ABSORPTION

Abstract

Similar works

Full text

Available Versions

Name not available

Crossref

D-Scholarship@Pitt

Name not available