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Biomedical subjects

Volker Mai

Publications and source records attributed to Volker Mai.

14 recordsLinked to original sources

Intestinal microbiota: a potential diet-responsive prevention target in ApcMin mice.

We previously reported that two dietary regimens, calorie restriction (CR) and a high olive oil-containing diet supplemented with a freeze-dried fruit and vegetable extract (OFV), reduced the development of intestinal adenomas in Apc(Min) mice by 57% and 33%, respectively, compared to control mice fed a defined diet ad libitum. The OFV diet was designed to have a strong effect on the composition of the intestinal microbiota through its high content of fiber, which represents a major source of fermentable substrate for the gut bacteria. We hypothesized that some of the observed effects of diet on intestinal carcinogenesis might be mediated by diet-related changes in the bacterial species that thrive in the gut. Therefore, we determined by fluorescent in situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) how the dietary interventions affected the composition of the intestinal microbiota, and we characterized specific microbiota changes that were associated with diet and reduced intestinal carcinogenesis. The OFV diet changed the overall composition of the intestinal microbiota, smaller changes were observed for the CR diet. Furthermore, we detected a 16S rDNA fragment associated with mice that did not develop polyps. Sequence analysis suggested that hitherto unidentified bacteria belonging to the family Lachnospiraceae (order Clostridiales) were its source. Thus, these bacteria may be an indicator of intestinal conditions associated with reduced intestinal carcinogenesis in Apc(Min) mice.

Adenoma↗

Monitoring of stool microbiota in subjects with diarrhea indicates distortions in composition.

We utilized denaturing gradient gel electrophoresis profiling to survey stool microbiota in 175 persons with diarrhea and 113 asymptomatic persons in a diarrhea surveillance study. Compared with healthy controls, the microbiota profiles in diarrhea cases more frequently exhibited decreased diversity and strong bands indicating the overgrowth of selected bacteria or bacterial groups.

Bacteria↗

Diarrheagenic Escherichia coli infection in Baltimore, Maryland, and New Haven, Connecticut.

BACKGROUND: Diarrhea remains a common complaint among US patients who seek medical attention. METHODS: We performed a prospective study to determine the etiology of diarrheal illness among patients and control subjects of all ages presenting to the emergency departments and outpatient clinics of 2 large academic hospitals in Baltimore, Maryland, and New Haven, Connecticut. We used molecular methods to detect the presence of diarrheagenic Escherichia coli pathotypes, including enteroaggregative E. coli (EAEC), as well as Shiga toxin-producing, cytodetaching, enterotoxigenic and enteropathogenic E. coli. RESULTS: Of the pathotypes sought, only EAEC was found in an appreciable proportion (4.5%) of case patients, and it was found more frequently among case patients than control subjects (P<.02). Surprisingly, EAEC was the most common bacterial cause of diarrhea in our population. EAEC was common in all age strata and was not associated with foreign travel or immunodeficiency. EAEC infection is frequently accompanied by fever and abdominal pain, though this did not happen more frequently in patients with EAEC infection than in patients with diarrhea due to other causes. CONCLUSIONS: Our data suggest that EAEC infection should be considered among persons with diarrhea that does not yield another known etiologic agent.

Adolescent↗

Urinary neutrophil gelatinase-associated lipocalcin in D+HUS: a novel marker of renal injury.

BACKGROUND: Diarrhea-associated hemolytic uremic syndrome (D+HUS) causes acute renal failure. Neutrophil gelatinase-associated lipocalcin (NGAL) is an early indicator of kidney injury. OBJECTIVE: To determine if urinary NGAL excretion is a biomarker of severe renal injury and predicts the need for dialysis in D+HUS. METHODS: Patients were randomly selected from among participants in the SYNSORB Pk trial. Urine samples were collected daily if available during the first week of hospitalization. NGAL levels were determined by ELISA. RESULTS: 34 children, age 5.9+/-3.9 yr, were studied; ten (29%) required dialysis. Patients were categorized based on urinary NGAL concentration within five days of hospitalization - <200 ng/ml and >or=200 ng/ml. Twenty patients (58%) had increased urinary NGAL excretion. The severity of D+HUS at enrollment was similar in the two groups. However, children with increased urinary NGAL levels had higher peak BUN and creatinine concentrations (P<0.01) and required dialysis more often, 9/20 versus 1/14 (P=0.024) compared to children with normal excretion. CONCLUSION: The majority of patients with D+HUS have renal tubular epithelial injury, as evidenced by elevated urinary NGAL excretion. Urinary NGAL levels below 200 ng/ml within five days of hospitalization may be an adjunctive marker that defines less severe renal involvement.

Acute-Phase Proteins↗

Negative energy balance induced by voluntary wheel running inhibits polyp development in APCMin mice.

Treadmill running of approximately 0.9 km/day has had inconsistent effects on spontaneous intestinal polyp development in C57BL/6J-Apc(Min)/J (Min) mice; the amount of energy expenditure and/or a lack of hormonal changes could account for this variability. The purpose of this study was to examine the effects of a negative energy balance induced by voluntary wheel running on polyps, insulin-like growth factor-1 (IGF-1) and corticosterone in Min mice. Seven-week-old male Min mice were randomly assigned to control (CON, n = 23) or wheel running (EX, n = 24) conditions for a 10-week study period. All mice had water and AIN-76A diet ad libitum for the first approximately 3 weeks on study, after which the EX group was pair-fed to the CON group to maintain a negative energy balance due to the exercise. EX mice voluntarily ran 3.8 km/day (2.7-6.0 km/day) (median, interquartile range) and weighed less than CON mice throughout the study. More CON mice died before the end of the study versus EX mice (26 versus 0%, P < 0.01). CON mice had significantly more polyps versus EX mice (21.6 +/- 1.5 versus 16.9 +/- 2.0, P < 0.01; mean +/- SE), and daily running distance in EX was inversely correlated with total polyp number (r = -0.70, P < 0.01). Urinary corticosterone output (P < 0.01) and serum IGF-1 were significantly higher in EX than CON (P < 0.001); however, total polyp number was unrelated to corticosterone (r = 0.05, P = 0.84) and IGF-1 (r = -0.01, P = 0.93). In this study, a negative energy balance produced by wheel running exercise and restricted feeding decreased polyp burden in male Min mice and appeared to have a dose-response effect on polyp number. Although EX affected IGF-1 and corticosterone, neither marker was related to total polyp number.

Animals↗

In vivo transduction of an Stx-encoding phage in ruminants.

We assessed the ability of a kanamycin-marked Stx phage to move into a commensal, ovine Escherichia coli strain in the ruminant gastrointestinal tract. Transduction was detected in 19/24 sheep tested, resulting in the recovery of 47 transductants. Subtherapeutic doses of the quinolone antibiotic enrofloxacin did not increase the rate of transduction.

Animals↗

Diet quality and subsequent cancer incidence and mortality in a prospective cohort of women.

BACKGROUND: We have previously reported on the utility of the Recommended Foods Score (RFS), a measure of overall diet quality, in detecting associations between diet and mortality in a cohort of older women. Using additional follow-up, we have now extended our analysis to detailed studies of associations between RFS and the mortality and incidence from common cancers. METHODS: The RFS, the sum of 23 recommended food items consumed at least weekly, was computed from a 62-item food frequency questionnaire completed at baseline by 42 254 women with a mean age of 61 years. Multivariate adjusted relative risk (RR) of cancer mortality and incidence of the cancers for which we were able to obtain data in relation to quartiles of RFS were examined using proportional hazards regression analyses after a median follow-up period of 9.5 years. RESULTS: We observed that RFS was inversely associated with total mortality (RR = 0.8; P < 0.001) cancer mortality (RR = 0.74; P < 0.001) as well as mortality from cancers of the breast (RR = 0.75; P < 0.06), colon/rectum (RR = 0.49; P < 0.01) and lung (RR = 0.54; P < 0.001). The risk of incident lung cancer (RR = 0.62; P < 0.001) was reduced in women in the highest vs the lowest quartile of RFS; for incident cancers of the breast, colorectum, endometrium, ovaries, and bladder, there was no RFS association. CONCLUSION: A dietary pattern reflecting a higher RFS was associated with decreased overall mortality in women, specifically cancers of the lung, colon/rectum, and to a lesser extent breast. Incidence was only decreased for lung cancers. These observations are consistent with the hypothesis that a high RFS dietary pattern, or associated lifestyle factors, might affect cancer progression and survival.

Coronary Disease↗

Colonic bacterial flora: changing understandings in the molecular age.

The human intestinal microbiota is a complex bacterial consortium that is critical to normal health. The microflora is present at concentrations of 10(11)-10(12) cells/g of intestinal contents; the number of species present may exceed 500, although exact numbers remain to be defined, due in part to the fact that <30% of microorganisms are culturable with current microbiologic methods. Molecular tools based on 16S rDNA sequence similarities such as fluorescent in-situ hybridization (FISH), denaturing gradient gel electrophoresis (DGGE), quantitative dot blot hybridization, restriction fragment length polymorphism (RFLP) and large scale 16S rDNA sequencing have helped to overcome limitations of conventional microbiological plating methods in studying the fecal microflora composition. However, these tools are just now beginning to be applied to understand the dynamics of this complex community, and its relationship to diet and human health. There is a need to understand both the limitations of the current data and the importance of moving forward with the best possible molecular and epidemiologic techniques as we deal with these critical questions.

Colon↗

Effects of a controlled diet and black tea drinking on the fecal microflora composition and the fecal bile acid profile of human volunteers in a double-blinded randomized feeding study.

Although diet has been clearly associated with human health many potential mechanisms remain undefined. For instance, although the intestinal bacterial microflora has long been postulated to contribute to human health, little is known about the effects of diet on the bacterial microflora composition and the specific contributions of the microflora to human health. Thus, we analyzed 1) changes in the fecal microflora composition by fluorescent in-situ hybridization (FISH) and denaturing gradient gel electrophoresis (DGGE) and 2) changes in the fecal bile acid profile, in a crossover feeding study that investigated the effects of black tea drinking on blood lipids in hypercholesterolemic volunteers. DGGE analysis shows that each study subject harbors a specific bacterial profile that exhibits little change over time. Change from a "free" living diet to the controlled study diet or to black tea drinking did not significantly change these bacterial profiles. FISH analysis revealed that even though black tea did not affect the specific bacterial groups that were analyzed, it did decrease the amounts of bacteria that were detected by the universal bacterial probe, but not by any of the specific probes. We did not detect any consistent effects of either diet or black tea drinking on the levels and proportions of fecal bile acids. Our results indicate that tea drinking affects some microflora components. Larger studies with well defined end points that control for the observed variation are needed to improve our understanding of the effects of diet on intestinal microflora and fecal bile acid profile.

Bile Acids and Salts↗

Dietary modification of the intestinal microbiota.

Humans harbor a consortium of commensal bacteria in their gut that are thought to be crucial for normal health. However, the extent of microbial diversity in the gut and the physiologic functions of the microflora have not yet been fully characterized. Molecular tools are now available to characterize the associations between diet, microflora composition, and health in greater depth. New molecular studies have confirmed earlier culture-based observations that diet has a role in the regulation of microflora composition. In the near future, new insight into these associations should allow for the design of specific diets aimed at improving health by modulating microflora.

Animals↗

Calorie restriction and diet composition modulate spontaneous intestinal tumorigenesis in Apc(Min) mice through different mechanisms.

We evaluated the effects of diet on intestinal tumorigenesis in male Apc(Min) mice by comparing AIN-76A diet fed ad libitum (CON); calorie intake restricted by 40% of the CON (CR); diet high in olive oil and supplemented with freeze-dried fruit and vegetable extracts (OFV); and diet high in total fat (HF). Compared with CON, the frequency of intestinal polyps was reduced by 57% by CR (P < 0.001) and by 33% OFV diet (P = 0.04). Both effective interventions reduced total body weight, lean mass, and fat mass and increased daily urinary corticosterone output, but only CR reduced serum insulin-like growth factor I and leptin. We conclude that dietary interventions can partially offset genetic susceptibility to intestinal carcinogenesis.

Animals↗

Dietary fibre and risk of colorectal cancer in the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort.

BACKGROUND: The hypothesis that increased intake of dietary fibre lowers the risk of colorectal cancer (CRC) has recently been weakened by results from cohort and intervention studies that did not detect such an association. We investigated the association between dietary fibre intake and risk of CRC in a cohort of women that prospectively answered a food frequency questionnaire (FFQ). METHODS: We studied 45 491 women in the Breast Cancer Detection Demonstration Project (BCDDP) follow-up cohort. A 62-item FFQ was administered from 1987 and 1989 to assess dietary intake. Participants received follow-up questionnaires (in 1992-1995 and 1995-1998) on which they reported incident cancers. Cases were also identified through searches of the National Death Index and state cancer registries. Cox proportional hazard regression was used to generate risk ratios and 95% CI for quintiles of total fibre intake and fibre subtypes. RESULTS: During a mean follow-up time of 8.5 years we identified 487 colorectal cancer cases. The 10th and 90th percentiles of dietary fibre intake were 5.4 g and 18.2 g respectively. For total fibre we observed no association with colorectal cancer (fifth versus first quintile, RR = 0.94, 95% CI: 0.71-1.23). Analyses by subgroup of fibre and by anatomical subsite did not reveal any stronger inverse associations. CONCLUSIONS: Within a cohort of older women characterized by a relatively low fibre intake, there was little evidence that dietary fibre intake lowers the risk of colorectal cancer.

Breast Neoplasms↗

Exercise and intestinal polyp development in APCMin mice.

PURPOSE: Epidemiological evidence suggests that physical activity protects against colon cancer. We previously used a mouse predisposed to intestinal polyps (APCMin) to evaluate this association and found the suggestion of fewer polyps in exercised males but not females. The present study was designed to further explore the potential exercise x sex interaction on polyp development and to begin to look at potential mechanisms. METHODS: Six-week-old APCMin mice (N = 60 males; 60 females) were randomly assigned to one of two groups by sex: treadmill running at 20 m.min-1, 5% grade, 45 min.d-1, 5 d.wk-1 (EX) or nonrunning controls (CON) (N = 30 per group). EX mice ran in running wheels while in quarantine (weeks 0-3), followed by treadmill running weeks 3-8. Body weights were measured weekly. Urine was collected at 5 wk and fasting blood at 7.5 wk. Body composition was measured, serum was frozen, and polyp number and size were measured at sacrifice. RESULTS: EX resulted in lower body weights (P < 0.01) and reduced fat mass (P < 0.01). Fasting glucose was lower in EX (P < 0.01), and leptin was lower in EX (P = 0.05) compared with CON. EX did not affect serum insulin-like growth factor-1 or urinary corticosterone. Total polyp number and size were not statistically different between groups; however, there were fewer jejunal polyps in EX (3.6 +/- 0.7, mean +/- SE) versus CON males (5.2 +/- 0.8; P = 0.04) and an even larger difference when only the consistent runners were kept in the analysis (2.7 +/- 0.5 in EX; P = 0.01). CONCLUSION: Despite favorable changes in body composition, blood glucose, and leptin, 8 wk of running resulted in only minor changes related to polyp development in male but not female APCMin mice.

Animals↗