The Effect of Bifidobacterium Administration

Transcription

1 The Effect of Bifidobacterium Administration in Patients with Leukemia Bifidobacteria Microflora Vol. 3(1), 29-33, 1984 Takashi KAGEYAMA, 1* Tsunesuke TOMODA, 2 and Yasuo NAKANO2 2nd Department of Internal Medicine,' and Department of Clinical Pathology,2 Osaka Medical College, Takatsuki, Osaka 569 (Received 18 May, 1983) The intestinal flora of patients with leukemia was changed by chemotherapy. In many cases, Klebsiella, Citrobacter, and Proteus vulgaris, etc., which are normally sparse, increased greatly. Anaerobic bacteria, especially Bacteroides, also increased. Many cases of Candida overgrowth were also observed. This imbalance of intestinal microorganisms was counteracted by oral Bifidobacterium administration. Endotoxin in the blood and indican in the urine were tested in leukemia patients. These tests were positive in many cases and were reduced by Bifidobacterium administration. Key words: Bifidobacterium; intestinal bacteria; Candida; leukemia; endotoxin; indican It is well known that patients with leukemia are prone to infectious diseases which may be lethal (7,16). The microorganisms responsible for these infectious diseases are chiefly common bacteria of the oral cavity, pharynx, larynx and digestive tract. This report describes variations in the populations of intestinal bacteria and of Candida in patients with leukemia, and the effect of Bifidobacterium milk administration. Endotoxin in blood and indican in urine were also examined under these conditions. 1. Materials and Methods The intestinal bacteria of 56 patients with leukemia were isolated from the feces and identified by Mitsuoka's method (11) and Bergy's classification (1). Candida was classified by Candida Check developed by Fukazawa (3). The number of bacteria in feces was calculated by several 10-fold step dilutions (4, 12) and recorded as log10/g feces. The types of leukemia tested in this study are listed in Table 1. The drugs used in the patients were chiefly: ordinary dosage of daunomycin, cytosin arabinoside, 6-MP, prednisolone etc., and also cyclophosphamide, busulfan, vincristine. Treatment was continued for more than two months in all cases. Endotoxin in blood was determined by the limulus lysate test (9) and indican in urine by Obermayer's method (6). Drinking water was substituted for by milk containing Bifidobacterium and Lactobacillus acidophilus (Morinaga Bifidus ). One milliliter of milk contained about 107 of each type of bacterium. Two hundred milliliters of milk was given to the patients every day in this experiment and the effect was assessed after three months. 2. Results The intestinal flora changed during the administration of antileukemic drugs with significant increases of Escherichia coli, Bacteroides and Veillonella. Bifidobacterium, Lactobacillus, and Streptococcus faecalis populations did not change (Table 2). When Bifido- 29

2 30 T. KAGEYAMA et al. bacterium was administered orally for 2-3 months, the intestinal bacterial balance returned to normal (Table 2). Table 3 shows the number of patients with leukemia with more than 106 colonies of Klebsiella, Citrobacter, Pseudomonas, or Proteus vulgaris per gram feces. The numbers of these microorganisms were greater in patients who did not receive Bifidobacterium than in those who were treated with Bifidobacterium. Candida counts in the feces of patients with leukemia are shown in Fig. 1. The counts were very high. The effect of Bifidobacterium administration on the number Table 1. Types of leukemia a Age: years. Males: 32 cases, females: 24 cases. of Candida in the feces of 16 patients receiving antileukemic therapy was examined. Eleven patients receiving antileukemic therapy without administration of Bifidobacterium were also examined as the control. All 27 patients had 105 Candida or more per gram of feces. The results are shown in Table 4. Bifidobacterium administration decreased the number of Candida. Patients having 108 Candida were not recognized, and in eight, the number of Candida was reduced to 104 or less. On the other hand, the number of Candida remained the same in the control patients not administered with Bifidobacterium. Namely, 11 cases not administerd with Bifidobacterium continuously had 105 Candida or more per gram of feces. The relationship between urine indican or blood endotoxin and Bifidobacterium administration during antileukemic therapy is shown in Table 5. Urine indican and blood endotoxin were positive in many patients receiving antileukemic therapy, and Bifidobacterium administration reduced the extent of the positive reaction. Table 2. Variation of intestinal bacteria during antileukemic therapya a Mean Logio number of intestinal bacteria per g feces. Table 3. Changes in minor members of intestinal bacteria during antileukemic therapya a Cases in which more than 106 colonies/g feces were observed.

3 BIFIDOBACTERIUM ADMINISTRATION IN LEUKEMIA 31 Fig. 1. Candida in feces of patients receiving antileukemic therapy. Table 4. Effect of Bifidobacterium administration on numbers of Candida in feces of patients receiving antileukemic therapya a Examination of 27 patients proved 105 or more Candida per gram of feces. Table 5. Urine indican and blood endotoxin during antileukemic therapy and effect of Bifidobacterium administration 3. Discussion Infectious diseases are among the most important of the complications arising in patients with leukemia, presumably because the abnormal number and functioning of leukocytes in leukemia permit the development of infections and because therapy with antileukemic drugs causes immunodeficiency. Septicemia, respiratory infection, pyelitis, etc. have been reported. The causal microorganisms are almost always members of the microflora of the pharynx, larynx and intestine. In cases of opportunistic infection, overgrowth of the usually small populations

4 32 T. KAGEYAMA et al. of intestinal becteria or Candida causes severe infectious diseases, and treatment with many antibiotics also results in Candida infection (5, 10). We have already described in our earlier reports (14,15) the variation and imbalance of intestinal bacteria during the administration of anticancer or immunosuppressive drugs. There have been few reports on the variation of intestinal bacteria in immunodeficiency states (2, 8, 13) and many problems require further investigation. In this study, we examined intestinal bacteria and Candida in the feces of patients with leukemia, and noted the effect of the administration of milk containing Bifidobacterium and Lactobacillus acidophilus. Increased numbers of the usually small groups of common intestinal bacteria (Klebsiella, Citrobacter, P. vulgaris, etc.) and of Candida were found in the feces of leukemia References patients. As regards the anaerobic bacteria, Bacteroides increased greatly. (1) Buchanan, R.E., and N.E. Gibbons Medications containing Bifidobacterium are Bergy's manual of determinating bacteriology, now being given clinically in an attempt to 8th Ed., Williams & Wilkins Co., Baltimore. inhibit the multiplication of pathogenic (2) Brown, W.R., D.C. Savage, R.S. Dubois, M.H. Aep, A. Mallory, and F. Kern Intestinal bacteria by lactate production, as well as to microflora of immunoglobulin deficient and improve digestion, absorption, and nutrition normal human subjects. Gastroenterol. 62: by the decomposition of lactose. It is known that bifidobacteria play an important (3) Fukazawa, Y., T. Shinoda, and T. Tsuchiya. role in protecting infants against intestinal Response and specificity of antibodies for Candidalbicans. J. Bacteriol. 95: infection. The authors previously reported (4) Gorbach, S.L., L. Nahas, P.I. Lerner, and L. their studies on the effect of Bifidobacterium Weinstein Studies of intestinal microflora. administration in preventing the imbalance I. Effect of diet, age, and periodic sampling on of intestinal microflora during immunosuppressive drug administration (12). numbers of fecal microorganisms in man. Gastroenterol. 53: In this study, administration of Bifidobacterium to patients with leukemia improved the Cancer 16: (5) Gruhn, J.G., and J. Sanson Mycotic infections in leukemic patients at autopsy. imbalance of intestinal microflora and prevented Candida overgrowth in the intestines. ment by laboratory methods, 16th Ed., p (6) Henry, J.B Clinical diagnosis and manage- Endotoxin in blood and indican in urine 593. W.B. Saunders Co., Philadelphia. are metabolic substances of intestinal bacteria, which are often present in leukemia J.A.M.A. 193: (7) Hersh, E.M., G.P. Bodey, B.A. Nies, and E.J. Freireich Causes of death in acute leukemia. patients. Both urine indican and blood (8) Hersh, T., M.H. Floch, H. J. Bixder, H.O. endotoxin were inhibited by Bifidobacterium Conn, R. Prizoxt, and H.M. Spiro Disturbance of the jejunal and colonic bacterial administration. It was thought that the flora in immunoglobulin deficiencies. Am. J. levels of these substances were normalized Clin. Nut. 23: as a result of the improvement of the imbalance of intestinal bacteria by Bifido- Detection of endotoxin in human blood. (9) Levin, J., P.A. Tomasulo, and R.S. Oser and bacterium administration. Leukemia may be a cause of immunological deficiency, which is further exacerbated by many kinds of antileukemic chemotherapy. As one side effect, variations of the intestinal flora occur. Candida overgrowth is also noted. Under these unfavorable circumstances, many potentially fatal infections may develop. The proliferation of Bifidobacterium in the intestines may restore the balance of intestinal microorganisms during the administration of antileukemic drugs. It has been demonstrated that Bifidobacterium administration can be used for the purpose of prophylaxis of many infections and improvement of secondary metabolic disturbance due to intestinal bacteria in leukemic patients undergoing antileukemic therapy.

5 BIFIDOBACTERIUM ADMINISTRATION IN LEUKEMIA 33 demonstration of an inhibitor. J. Lab. Clin. Med. 75: (10) Mirsky, H.S., and J. Cuttner Fungal infection in acute leukemia. Cancer 30: (11) Mitsuoka, T A color atlas of anaerobic bacteria, Sobunsha, Tokyo (in Japanese). (12) Schaedler, R.W., R. Dubos, and R. Costello The development of the bacterial flora in the gastrointestinal tract of mice. J. Exp. Med. 122: (13) Taylor, G.R., K.D. Kropp, and T.C. Molina Microflora analysis of a child with severe combined immunodeficiency. Infect. & Immun. 19: (14) Tomoda, T., N. Kaneda, and T. Kageyama Variation of intestinal bacteria during administration of immunosuppressive drugs and anticancer drugs (I). Jpn. J. Gastroenterol. 75: (in Japanese with English summary). (15) Tomoda, T., Y. Nakano, and T. Kageyama Variation of intestinal bacteria during administration of immunosuppressive of anticancer drugs (II). Jpn. J. Gastroenterol. 77: (in Japanese with English summary). (16) Viola, M.V Acute leukemia and infection. J.A.M.A. 201: