SIBO Association with Nutrition Intake

JAGS 51:768–773, 2003© 2003 by the American Geriatrics Society 0002-8614/03/$15.00Prevalence of Small Bowel Bacterial Overgrowth andIts Association with Nutrition Intake in NonhospitalizedOlder AdultsAlexandr Parlesak, PhD,* Birgit Klein, MD, † Kerstin Schecher, MSc,*J. Christian Bode, MD, † and Christiane Bode, PhD*OBJECTIVES: To determine the prevalence of small bowelbacterial overgrowth (SBBO) in older adults and to assesswhether SBBO is associated with abdominal complaintsand nutrient intake.DESIGN: Cross-sectional survey.SETTING: Eight senior residence sites in Stuttgart,Germany.PARTICIPANTS: Older adults living independently in se-nior residence houses.MEASUREMENTS: The prevalence of SBBO was mea-sured in 328 subjects, of whom 294 were aged 61 andolder, by measuring hydrogen concentration (parts permillion; ppm) in exhaled air after ingestion of 50 g glu-cose. Anthropometric data were obtained and nutritionalstatus was recorded with a computer-aided diet history.RESULTS: The prevalence of a positive hydrogen breathtest ( Ͼ 10 ppm increase) was 15.6% in older adults, com-pared with 5.9% in subjects aged 24 to 59. The intake ofinhibitors of gastric acid production contributed signifi-cantly to the high prevalence of a positive breath test inolder adults, which was associated with lower bodyweight, lower body mass index, lower plasma albuminconcentration, and higher prevalence of diarrhea. Subjectswith a positive hydrogen breath test consumed signifi-cantly less fiber, folic acid, and vitamins B 2 and B 6 thanthose without. No difference was observed in the intake ofenergy, protein, fat, or carbohydrates.CONCLUSION: Prevalence of SBBO is associated withreduced body weight, which is paralleled by reduced in-take of several micronutrients. Malabsorption resultingfrom diarrhea might be an aggravating factor contributingto weight loss in these subjects. J Am Geriatr Soc 51:768–773, 2003.Key words: small bowel bacterial overgrowth; hydrogen breath test; older adults; nutritional status mall bowel bacterial overgrowth (SBBO) has been found to be associated with a large number of anatomic dis-orders leading to stasis of intestinal contents. 1,2 Two de-cades ago, SBBO was observed in studies of small numbers of selected older patients with anatomically normal bowels and was assumed to be an important cause of occult or overt malabsorption in this age group. 3,4 In consecutive studies, the prevalence of SBBO in healthy older people was found to be higher than in healthy young subjects, 4–8 but the reported prevalence varied, with values ranging from 20% 7 to 56%. 8 The varying prevalence may be related to small sample numbers, selected groups of older adults, and, perhaps more importantly, different methods used to identify SBBO, such as 14 carbon (C)-bile acid breath test, hydrogen (H 2 ) breath test using glucose or lactulose as substrate, and cultures of aspirates from the duodenum or upper jejunum. 5–8 The aim of the present study was to assess the preva-lence of SBBO using glucose/H 2 breath test in a large group of older adults living in residential care homes and to inves-tigate whether SBBO is associated with signs of abdominal complaints. The association between the prevalence of SBBO and the intake of nutrients was also studied. SUBJECTS AND METHODS The study was performed in accordance with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by the local ethics committee. Written informed consent was received from all participants. Subjects Older adults of both sexes (aged 61–94; mean Ϯ standard deviation (SD) ϭ 76.9 Ϯ 7.3) from eight senior residence sites in Stuttgart were invited to participate in the study. In these senior residences, subjects lived in their own apart-ments and did not receive assistance with activities such as From the *Hohenheim University (140), Department of Physiology ofNutrition, Stuttgart, Germany; and† Department of Internal Medicine I,Robert-Bosch-Krankenhaus, Stuttgart, Germany.The work was generously supported by Nestlé Ltd.Address correspondence to Alexandr Parlesak, Ph. D., HohenheimUniversity (140), Department of Physiology of Nutrition, Garbenstraße 28,D-70593 Stuttgart, Germany. E-mail: parlesak@uni-hohenheim.de SJAGS JUNE 2003–VOL. 51, NO. 6SMALL BOWEL BACTERIAL OVERGROWTH IN THE OLDER ADULT769toileting, dressing, and bathing and were all able to walk and to eat without help. Meal and laundry services were of-fered, but none of the study participants required skilled nursing care on a regular basis. Most of the participants were living in the residences, but nonresidents were in-cluded in the study upon request if they did not require skilled nursing care or hospitalization (n ϭ 42). People younger than 60 (24–59; mean Ϯ SD ϭ 33.6 Ϯ 11.2), weight 70.1 Ϯ 15.0 kg and body mass index (BMI) ϭ 23.0 Ϯ3.9 kg/m2, were recruited using notices in public places. Ex-clusion criteria were bacterial or viral infections or anti-biotic treatment during the preceding 3 weeks; any type of acute or chronic inflammatory disease; any form of gastric or intestinal surgery; malignancies; and significant meta-bolic, hepatic, pancreatic, or renal disease. Detailed data on age and sex distribution of volunteers recruited for this study are given in Table 1.H2 Breath TestSubjects were asked to refrain from smoking for 24 hours and during the test. Those subjects who regularly took lactulose or other laxatives were asked to omit these com-pounds for 24 hours before the test. Subjects fasted over-night (12 hours) and during the test. The breath tests were performed between 7:30 and 8:30 a.m. Subjects remained sedentary throughout the test period and were asked to avoid hyperventilation. Two mouthwashes were per-formed 10 minutes before testing with 40 mL chlorhexi-dine solution (0.2% weight/vol).End-expiratory breath samples were collected 10 min-utes and 5 minutes before and every 10 minutes for 1 hour after the ingestion (within 3–5 minutes) of 50 g glucose dissolved in 200 mL of water. Thereafter, one additional breath sample was taken after 15 minutes. H2 gas concen-tration in exhaled air was measured with a portable monitor (Micro H2, DEGO, Nagold, Germany). The monitor was cal-ibrated before each measurement with a standard hydrogen gas concentration of 103 parts per million (ppm) (DEGO).A pathologic result of the H2 breath test was taken as a rise of more than 10 ppm over baseline within 75 minutes. As a second measure, area under the H2 curve (AUC) for the period 0 to 75 minutes was calculated using the formula:In this formula, c(H2) assigns the concentration (ppm) ofhydrogen in exhaled air, and t represents the time (min-utes) passed since the ingestion of glucose.Assessment of Nutritional IntakeTo assess the nutritional intake, a trained nutritionistinterviewed subjects using a shortened version of acomputerized method of a diet history (EBIS software,EϩD Partner, Neu-Aspach, Germany). The program is based on the G erman Food and Nutrient Data Base,which includes 11,000 food items and recipes. The in-terview method has been validated against observednutritional intake.9 The interview included questionsabout the frequency and amount of alcohol consump-tion and the amount of liquid consumed daily. All sub-jects were asked about their smoking habits and intakeof drugs or vitamin supplements. All additional supple-mentations were noted in the evaluation of the nutri-tional intake.Demographic and Clinical CharacteristicsIn addition to age and sex, information about weight,height, BMI, complete list of diagnoses, bowel habits (di-arrhea, constipation), dyspeptic symptoms, known aller-gies, physical exercise (frequency, intensity), and subjec-tive rating of state of health was collected from allsubjects.Hematology and Clinical ChemistryVenous blood samples were taken after an overnight fastbetween 7:30 and 8:30 a.m. on the day the breath test wasperformed on 68 subjects (40 without SBBO, 28 withSBBO). The following parameters were measured: erythro-cyte sedimentation rate; numbers of leukocytes, erythrocytesand platelets; hemoglobin; mean corpuscular volume; andserum concentrations of C-reactive protein, albumin, trans-ferrin, creatinine, transaminases (alanine-amino transferase,aspartate-amino transferase), ␥-glutamyltranspeptidase, and alkaline phosphatase.StatisticsIf not indicated otherwise, values are given as mean Ϯ SD. Values were compared with the Student t test or with the nonparametric Mann-Whitney U test, if data were not normally distributed or homogeneity of variances was not given. If appropriate, a multiple regression analysis was used to distinguish the influence of different variables on certain parameters. Significances of correlation were cal-culated with the Spearman rank sum test. Cross tabulation tables were evaluated with Pearson chi-square test or the Fisher exact test (2 ϫ 2 tables).RESULTSIf a positive result of the glucose H2 breath test (positive breath test (PBT)) was taken as a rise of more than 10 ppm over the baseline in all subjects investigated, the prevalence of a PBT was 14.6% (Table 1). In all volunteers with a PBT, theAUC c H2()t()dttϭ075ΎϭTable 1. Effect of Age and Sex on the P revalence of a Positive Breath Test OutcomeϾ10 ppm H2*Ͼ20 ppm H2†Characteristic n n (%)Total group32848 (14.6)36 (11.0) Female24336 (14.8)27 (11.1) Male8512 (14.1)9 (10.6) Age20–5934 2 (5.9) 2 (5.9)61–9429446 (15.6)34 (11.6) 61–73959 (9.4) 6 (6.3)74–7910417 (16.3)14 (13.5) 80–94 9520 (21.1)14 (14.7) Note: Maximum increase in hydrogen (H2) concentration in exhaled air after glu-cose ingestion exceeded *10 parts per million (ppm)) and †20 ppm.770PARLESAK ET AL.JUNE 2003–VOL. 51, NO. 6JAGS increase of at least 11 ppm H2 in exhaled air occurred before50 minutes after glucose ingestion. The values for womenand men did not differ. The prevalence for the older adults(Ն61) was more than twice that observed in the youngergroup (15.6% vs 5.9%; Pϭ .095) (Table 1). Within thegroup of adults aged 61 and older, a PBT was more thantwice as frequent (Pϭ .048) in volunteers aged 80 to 94(upper tertile) than in those aged 61 to 73 (lower tertile). Theprevalence of a PBT in the oldest adults (Ն80) was more than3.4 times higher than that of the group of the study partici-pants younger than 60 (21.1% vs 5.9%, Pϭ .033).If a positive result of the test was taken as a rise of 20ppm over the baseline, the prevalence for the total groupwas only moderately smaller (n ϭ 36: 11.0%) than the valueif a positive test was taken as an increase of more than 10ppm over the baseline. Moreover, the relative increase in theprevalence of a PBT with increasing age in adults aged 61and older persisted with the 20 ppm H2 criteria (Pϭ .048).In the group with a PBT, the basal H2 values, the max-imum increase of H2 concentration within 75 minutes, and the total amount of exhaled hydrogen over 75 minutes (represented by the AUC) were markedly higher than those of the group without a PBT (Table 2; Figure 1). The age of the study participants correlated significantly with the maximum increase in H2 concentration in exhaled air (Spearman rϭ 0.166, Pϭ .003) and to the AUC values (rϭ 0.175, Pϭ .001). Multiple regression analysis for po-tentially relevant factors for PBT prevalence (sex, intake of drugs inhibiting gastric acid production, smoking, BMI, body weight) revealed a moderate correlation between the maximum increase and age (␤ϭ 0.131, Pϭ .030) and a pronounced one with the intake of drugs inhibiting gastric acid production (␤ϭ 0.188, PϽ .001). In the subgroup of volunteers taking drugs that block gastric acid production (H2-receptor antagonists, n ϭ 9, or proton pump inhibi-tors, n ϭ 3), a significantly higher prevalence of PBT was found (6/12 ϭ 50% vs 39/278 ϭ 14.0%; Pϭ .004). There was no association between a PBT and the intake of other drugs such as aspirin, pain killers, or sedatives.Subjects with a PBT more frequently reported loose stool/diarrhea than those without (21.7% vs 10.7%, re-spectively; Pϭ .024), but no significant differences were found with respect to constipation (26.7% vs 21.4%, re-spectively; Pϭ .272) and dyspeptic complaints (73.9% vs 67.3%, respectively; Pϭ .242). The regular intake of lax-atives had no influence on the outcome of the H2 breath test (26.1% with a PBT vs 26.7% without, Pϭ .544). The occurrence of a PBT was associated with lower mean body weight and lower values of BMI (Table 3). No significant differences were found regarding other complaints or clin-ical findings as listed in detail in the Methods section.A PBT was associated significantly more frequently with average intake of less than three cups/glasses liquid per day than with consumption of three glasses or more (46% vs 14%, Pϭ .008). Other data on the nutritional in-take of older subjects with and without a PBT are summa-rized in Table 4. The occurrence of a PBT was associated with a significantly lower intake of fiber, folate, and vita-mins B2 and B6. The mean consumption of micronutrients was always lower in subjects with a PBT than in those without. Although the differences in the intake of most mi-cronutrients in these subjects (Ϫ3.8 to Ϫ15.8%) did not reach significance, they were more pronounced than those of macronutrients (protein, fat, carbohydrates: Ϫ0.2 to Ϫ4.0%). Older adults without a PBT were consuming vi-tamin supplements in moderation more frequently than those with a PBT, but the difference was not significant (55.7% vs 43.5%, respectively; Pϭ .087).No significant differences in hematological values be-tween subjects with and without a PBT were found. The concentration of serum albumin in older subjects was sig-nificantly lower in subjects with a PBT than in subjects without (Table 3). No significant differences were found for any other clinical-chemical values, which were all within the normal range.DISCUSSIONJejunal cultures have been proposed as the criterion stan-dard in the detection of SBBO.1,10,11 The reliability of thisapproach in diagnosing SBBO has been questioned be-Figure 1. Time course of hydrogen (H2) concentration in ex-haled air in elderly subjects from groups with (᭹; n ϭ 46) and without (᭺; n ϭ 248) small bowel bacterial overgrowth after glucose ingestion; values are given as mean Ϯ standard error of the mean.Table 2. Values of Hydrogen Concentration in Exhaled Air in Subjects with and without a P ositive Hydrogen Breath Test (⌬c(H2) Ͼ10 parts per million)Positive HydrogenBreath TestNo (n ϭ 248)Yes (n ϭ 46)Value Mean Ϯ Standard Deviation P-value Basal value, ppm 6.3 Ϯ 8.614.2 Ϯ 17.5Ͻ.001 Mean increase, ppm 3.0 Ϯ 2.842 Ϯ 31Ͻ.001 Area under the curve,ppm ϫ minutes170 Ϯ 1671,499 Ϯ 1,075Ͻ.001Note: Subjects aged 61 and older.ppm ϭ parts per million.JAGS JUNE 2003–VOL. 51, NO. 6SMALL BOWEL BACTERIAL OVERGROWTH IN THE OLDER ADULT 771cause of bacterial contamination derived from saliva 12 anddiffering results obtained if jejunal samples are taken atdifferent times or from different sites.13 Despite thesepoints of criticism, bacteriological analysis of aspirated intes-tinal fluid has widely been used to estimate specificity andsensitivity of indirect techniques to diagnose SBBO.5,6,10,14,15The discomfort of intubation markedly hampers the bacteri-ological analysis of aspirated intestinal fluid for studies inhealthy subjects. To overcome this problem, indirect meth-ods such as measurement of 14carbon dioxide (CO 2) in ex-pired breath samples after intake of 14C-labeled bile saltsor xylose to detect SBBO were proposed.1,2,14 To avoid theuse of radioactive isotopes, H 2 breath tests have been de-veloped that rely on the production of hydrogen gas afterexposure of fermentable substrate to high numbers of bac-teria in the small intestine.16 Glucose has become the pre-ferred substrate for H 2 breath tests to diagnose SBBO,mostly using a 50-g glucose challenge.6,12,16,17 If an increaseof more than 10 ppm within 1 to 2 hours is taken as an in-dicator for the diagnosis of SBBO, the specificity of the testis sufficient for screening studies (77–100%).6,10,12,14,16,18 Alow specificity of this version of the H 2 breath test was re-ported in only one study with 30 older patients, 20 of whom had increased bacterial counts in aspirates of the upper small intestine.19 Most authors found the sensitiv-ity of the glucose H 2 breath (67–98%) test to be accept-able for screening studies 12,14,16,18 but to be only 62%10 and even less 6 by others.The test conditions (dose of glucose, duration of test period, and cutoff point) used in the present study were comparable with those of recent other reports.14,18 The early onset of the increase of hydrogen concentration in exhaled air in all volunteers with a PBT (within 50 min-utes after glucose ingestion) makes the occurrence of false-negative results as a consequence of delayed gastric empty-ing unlikely. Several authors have set a cutoff for the in-crease in H 2 concentration to diagnose SBBO of 10ppm.10,14,17,19 Others suggested a cutoff of 20 ppm.6,16,18 In the present study, the prevalence of the PBT did not differ significantly if a cutoff value of 20 ppm was used, com-pared with the values obtained for a cutoff of 10 ppm (11.0% vs 14.6% in the total group, respectively). Table 4. Mean Daily Nutrient Intake in Subjects with and without a Positive Hydrogen Breath Test (⌬c(H 2) Ͼ10 parts per million)Positive Hydrogen Breath TestDRI Women/Men No Yes NutrientMean Ϯ Standard Deviation P -value Energy, kcal1,948 Ϯ 3751,906 Ϯ 402.499Protein, g70.0 Ϯ 15.367.7 Ϯ 18.2.384Fat, g81.9 Ϯ 22.381.8 Ϯ 22.7.961Carbohydrates, g217 Ϯ 51.1209 Ϯ 54.7.310Fiber, g24.1 Ϯ 7.721.4 Ϯ 8.4.037Alcohol, g5.5 Ϯ 8.66.4 Ϯ 11.0.584Vitamin C, mg75/90134 Ϯ 79115 Ϯ 67.123Vitamin B 1, mg1.1/1.2 1.09 Ϯ 0.29 1.05 Ϯ 0.30.376Vitamin B 2, mg1.1/1.3 1.42 Ϯ 0.28 1.29 Ϯ 0.29.047Vitamin B 6, mg1.5/1.7 1.56 Ϯ 0.45 1.40 Ϯ 0.44.032Folic acid, ␮g400/400111 Ϯ 3799 Ϯ 32.043Vitamin E, mg15/1511.7 Ϯ 6.29.9 Ϯ 5.8.067Vitamin A, mg 0.70/0.901.17 Ϯ 0.42 1.11 Ϯ 0.43.386Note: Subjects aged 61 and older. DRI ϭ dietary reference intakes (daily recommended intakes released for adults aged 50 and older by the Food and Nutrition Board, In-stitute of Medicine.39–41Table 3. Characteristics of Subjects with and without a Positive Hydrogen Breath Test (⌬c(H 2) Ͼ10 parts per million)Positive Hydrogen Breath TestWithout (n ϭ 248)With (n ϭ 46)CharacteristicMean Ϯ Standard Deviation P -value Body weight, kg67.9 Ϯ 12.163.5 Ϯ 13.7.025Body mass index, kg/m 224.9 Ϯ 3.823.4 Ϯ 3.6.014Serum albumin, g/dL3.98 Ϯ 0.40 3.61 Ϯ 0.55.003Transferrin, mg/dL247 Ϯ 41244 Ϯ 73.832Total leukocyte count ϫ109/L2.01 Ϯ 0.611.95 Ϯ 0.59.756Note: Subjects aged 61 and older.772PARLESAK ET AL.JUNE 2003–VOL. 51, NO. 6JAGSThe mean basal H2 exhalation was significantly higher in subjects classified as having SBBO than in those with-out. Other authors reported similar observations.10,20 Using a highly standardized protocol (diet, refrain from smok-ing, oral hygiene), the basal H2 value was even proposed as an adequate measure for the diagnosis of SBBO,20 but others have not confirmed the validity of this simple test to detect SBBO.14,19The results of the present study confirmed an in-creased prevalence of SBBO in older subjects described in earlier reports,4–8,19,21,22 but the prevalence of SBBO in older adults in most earlier reports was markedly higher than in the present study if SBBO can be assumed to be present by a PBT. Small numbers of subjects studied4–6,19,22 and the fact that patients in hospitals were studied who had more or less pronounced gastrointestinal symptoms5,6,19,21,22 might explain the higher prevalence of SBBO in these ear-lier studies. In other studies, lactulose H2 breath test22 or a combination of lactulose H2 breath test and 14C-bile acid-breath test7 were used, which may cause false-positive re-sults because of accelerated passage of substrate into the colon, even in normal subjects.In a recent study using a similar protocol to that of the present study, the prevalence of SBBO was comparable to the present results. In that study, in 62 older adults living in residential care homes, the prevalence of SBBO was found to be 14.5% when a cutoff for H2 of 20 ppm was used.23 On the basis of the latter findings and the results of the present study, it seems likely that the prevalence of SBBO in unselected older subjects has been overestimated in some of the earlier studies.Gastric acid is an important barrier to bacterial over-growth in the small intestine. Hypochlorhydria, induced by H2-receptor antagonists or proton pump inhibitors, re-sults in bacterial proliferation in the stomach and upper small intestine.1,2,24–27 No increase in the number of positive glucose-H2 breath tests was observed in one study of a small group of older patients in which 59% of the 22 control sub-jects without omeprazole treatment had a positive test.28 In the present study in normal older volunteers, prolonged pharmacological suppression of acid production distinctly increased the prevalence of pathological breath tests.Potential risk factors for SBBO in older adults remain poorly defined. Reduced gastric acid secretion due to the increased prevalence of atrophic gastritis in the elderly has been assumed to contribute to the increased prevalence of SBBO,29 but it has been reported that most healthy older people actually maintain normal gastric acid secretion.30 Impaired gastrointestinal motility is also a risk factor for the development of SBBO. Although constipation is a common symptom in older adults,31,32 little is known about changes in motility of the small bowel in the older adults. The reduced liquid intake and the lower consump-tion of fiber by subjects with SBBO observed in this study might be a risk factor for SBBO development by reducing gut motility. These risk factors might be of special impor-tance for adults aged 80 and older because the prevalence of SBBO in these subjects is twice as high as in persons aged 61 to 73. Alcohol abuse, which has been shown to be associated with a marked risk in developing SBBO,33,34 was not observed in this study population.In the subjects included in this study who were inde-pendently living, normal older persons, SBBO was associ-ated with lower mean body weight and BMI and increased occurrence of diarrhea. Subjects with SBBO consumed in the average significantly less folic acid, vitamin B2, and vita-min B6 than those without SBBO. The difference in the in-take of micronutrients was more pronounced than the dif-ference in energy and macronutrient consumption, which may indicate differences in the quality of food consumed by both groups.Noteworthy in this context is the low intake of folate in both groups (25–28% of the recommended drug intake value) (Table 4). From the results of the present study, it cannot be determined whether the lower nutrient intake is a cause or a consequence of SBBO. A high prevalence of deficiency for some of the micronutrients mentioned above (folate and vitamins B2/B6) has been reported in the el-derly.35,36 A lowered intake of folate37 and vitamin B638 might affect T-cell and immune function, which in turn might weaken host defenses against SBBO. Malabsorption that is frequently associated with SBBO might enhance a deficiency in these micronutrients as well as macronutri-ents and might be the predominant cause of diarrhea in these subjects. 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