Soup Kettle Topics: Gut Probotics

Title: Microflora-Associated Characteristics in Faeces from Allergic and Nonallergic Infants
Author: Bottcher, M. F.; Nordin, E. K.; Sandin, A.; Midtvedt, T.; Bjorksten, B.; (Date: Nov, 2000)
Journal: Clin Exp Allergy; V. 30; Issue: 11; Pages: 1590-6

Abstract: BACKGROUND: The prevalence of allergic diseases has increased particularly over the past 30-40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation. OBJECTIVE: The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11-18), through analysing microflora-associated biochemical markers in faeces. METHODS: Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically. RESULTS: The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups. CONCLUSION: The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora that may disturb the development of a normal Th1-/Th2-balance in allergic children.
Notes: Journal Article
Author Address: Department of Health and Environment, Division of Paediatrics, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden.

Title: Probiotics, Prebiotics, and Synbiotics: Approaches for Modulating the Microbial Ecology of the Gut
Author: Collins, M. D.; Gibson, G. R.; (Date: May, 1999)
Journal: Am J Clin Nutr; V. 69; Issue: 5; Pages: 1052S-1057S

Abstract: The microbiota of the human large intestine influences health and well-being. Whereas it has long been accepted that gut bacteria play a role in host pathogenesis, current opinion is that certain microflora components can have beneficial effects on gastroenteritis resistance, blood lipids, antitumor properties, lactose tolerance, and gastrointestinal immunity. It is postulated that in the infant gut an elevated bifidobacterial count may be associated with health advantages that breast-fed infants may have over formula-fed infants. Whereas beneficial aspects of the human gut flora still need definitive confirmation and mechanistic explanations, there is now interest in modulating the composition of gut flora such that a potentially more remedial community exists. This may be achieved through the targeted use of dietary supplementation. This article provides an overview of how probiotics, prebiotics, and synbiotics may contribute toward nutritional modulation of the gut microecology, with emphasis on the neonatal intestine where appropriate. The use of modern molecular methods, as an essential step forward for assessing the validity and accuracy of the modulatory approach, is also discussed.
Notes: Journal Article
Review, Tutorial
Author Address: Microbiology Department, the Institute of Food Research, Reading, United Kingdom.

Title: Protective Nutrients and Bacterial Colonization in the Immature Human Gut
Author: Dai, D.; Walker, W. A.; 1999)
Journal: Adv Pediatr; V. 46; Pages: 353-82

Abstract: The normal human microflora is a complex ecosystem that is in part dependent on enteric nutrients for establishing colonization. The gut microbiota are important to the host with regard to metabolic functions and resistance to bacterial infections. At birth, bacterial colonization of a previously germ-free human gut begins. Diet and environmental conditions can influence this ecosystem. A breast-fed, full-term infant has a preferred intestine microbiota in which bifidobacteria predominate over potentially harmful bacteria, whereas in formula-fed infants, coliforms, enterococci, and bacteroides predominate. The pattern of bacterial colonization in the premature neonatal gut is different from that in the healthy, full-term infant gut. Those infants requiring intensive care acquire intestinal organisms slowly, and the establishment of bifidobacterial flora is retarded. A delayed bacterial colonization of the gut with a limited number of bacterial species tends to be virulent. Bacterial overgrowth is one of the major factors that promote bacterial translocation. The aberrant colonization of the premature infant may contribute to the development of necrotizing enterocolitis. Breast-feeding protects infants against infection. Oligo-saccharides and glycoconjugates, natural components in human milk, may prevent intestinal attachment of enteropathogens by acting as receptor homologues. Probiotics and prebiotics modulate the composition of the human intestinal microflora to the benefit of the host. These beneficial effects may result in the suppression of harmful microorganisms, the stimulation of bifidobacterial growth, or both. In the future, control and manipulation of the bacterial colonization in the neonatal gut may be a new approach to the prevention and treatment of intestinal infectious diseases of various etiologies.
Notes: Journal Article
Review, Academic
Author Address: Shanghai Institute for Pediatric Research, Shanghai Second Medical University, China.

Title: Could Oligosaccharide Supplementation Promote Gut Colonization with a Beneficial Flora in Preterm Infants?
Author: Danan, C.; Huret, Y.; Tessedre, A. C.; Bensaada, M.; Szylit, O.; Butel, M. J.; (Date: Feb, 2000)
Journal: J Pediatr Gastroenterol Nutr; V. 30; Issue: 2; Pages: 217-9

Notes: Journal Article
Author Address: Faculte des Sciences Pharmaceutiques et Biologiques, Laboratoire de Microbiologie, Universite Rene Descartes, Paris, France.

Title: Interactions Mediating Bacterial Translocation in the Immature Intestine
Author: Duffy, L. C.; (Date: Feb, 2000)
Journal: J Nutr; V. 130; Issue: 2S Suppl; Pages: 432S-436S

Abstract: Systemic disease caused by transmucosal passage of enterovirulent bacteria and toxins from the gut lumen into the mesenteric lymph nodes (MLN) is reviewed, with particular concern for bacterial interactions in the developing gut of premature newborns. Anaerobic bacteria are rarely observed to translocate to the MLN. Bifidobacterial strains have been tested for their abilities to adhere to enterocyte-like Caco-2 cells in culture. We have investigated the inhibitory effect of adherent human bifidobacterial strains against colonization by a number of diarrheagenic bacteria (Escherichia coli 0157; Salmonella typhimurium) and viruses (murine and rhesus rotavirus), in various in vitro and in vivo models. The phagocytic cell (macrophage) may be a key factor in bacterial translocation (BT). Human breast milk contains abundant bioactive substances (immunologic, nutritional) that provide protective effects through inhibition of bacterial overgrowth and BT. New biotherapeutic therapies that stimulate beneficial anaerobic microflora (Lactobacillus, Bifidobacterium) are promising avenues of research to combat BT in disease treatment.
Notes: Journal Article
Review, Tutorial
Author Address: Woman and Children’s Health Research Foundation, Children’s Hospital of Buffalo, SUNY, NY 14222, USA.

Title: Probiotics and Dietary Fiber: The Clinical Coming of Age of Intestinal Microecology
Author: Floch, M. H.; Moussa, K.; (Date: Sep, 1998)
Journal: J Clin Gastroenterol; V. 27; Issue: 2; Pages: 99-100

Notes: Editorial

Title: Modification of the Intestinal Microflora Using Probiotics and Prebiotics
Author: Fuller, R.; Gibson, G. R.; 1997)
Journal: Scand J Gastroenterol Suppl; V. 222; Pages: 28-31

Abstract: Probiotics and prebiotics modulate the composition of the human gut microbiota. The beneficial effects may result from suppression of harmful microorganisms or stimulation of organisms which contribute in a positive way to the nutrition and health of the host. Both types of supplement represent an attempt to reconstitute the gut flora to its normal composition which has been adversely affected by dietary and environmental stresses.
Notes: Journal Article
Author Address: Institute of Food Research, Reading, UK.

Title: Probiotics
Author: Guarner, F.; Schaafsma, G. J.; (Date: Feb 17, 1998)
Journal: Int J Food Microbiol; V. 39; Issue: 3; Pages: 237-8

Notes: Congresses
Author Address: Digestive System Research Unit, Hospital General Vall d’Hebron, Barcelona, Spain.

Title: Distinct Patterns of Neonatal Gut Microflora in Infants in Whom Atopy Was and Was Not Developing
Author: Kalliomaki, M.; Kirjavainen, P.; Eerola, E.; Kero, P.; Salminen, S.; Isolauri, E.; (Date: Jan, 2001)
Journal: J Allergy Clin Immunol; V. 107; Issue: 1; Pages: 129-34

Abstract: BACKGROUND: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. OBJECTIVE: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. METHODS: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. RESULTS: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing (P =.005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 x 10(7) [3.8-22.9 x 10(7)] vs 3.3 x 10(7) [1.8-6.1 x 10(7)], P =.04) and tended to have fewer bifidobacteria (1.8 x 10(9) [0.4-7.6 x 10(9)] vs 6.1 x 10(9) [2.5-14.6 x 10(9)], P =.11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia (P =.03). The differences were not detected by bacterial cultivation. CONCLUSION: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode.
Notes: Journal Article
Author Address: Department of Pediatrics, University of Turku, Turku.

Title: Probiotics in Primary Prevention of Atopic Disease: A Randomised Placebo-Controlled Trial
Author: Kalliomaki, M.; Salminen, S.; Arvilommi, H.; Kero, P.; Koskinen, P.; Isolauri, E.; (Date: Apr 7, 2001)
Journal: Lancet; V. 357; Issue: 9262; Pages: 1076-9

Abstract: BACKGROUND: Reversal of the progressive increase in frequency of atopic disease would be an important breakthrough for health care and wellbeing in western societies. In the hygiene hypothesis this increase is attributed to reduced microbial exposure in early life. Probiotics are cultures of potentially beneficial bacteria of the healthy gut microflora. We assessed the effect on atopic disease of Lactobacillus GG (which is safe at an early age and effective in treatment of allergic inflammation and food allergy). METHODS: In a double-blind, randomised placebo-controlled trial we gave Lactobacillus GG prenatally to mothers who had at least one first-degree relative (or partner) with atopic eczema, allergic rhinitis, or asthma, and postnatally for 6 months to their infants. Chronic recurring atopic eczema, which is the main sign of atopic disease in the first years of life, was the primary endpoint. FINDINGS: Atopic eczema was diagnosed in 46 of 132 (35%) children aged 2 years. Asthma was diagnosed in six of these children and allergic rhinitis in one. The frequency of atopic eczema in the probiotic group was half that of the placebo group (15/64 [23%] vs 31/68 [46%]; relative risk 0.51 [95% CI 0.32-0.84]). The number needed to treat was 4.5 (95% CI 2.6-15.6). INTERPRETATIONS: Lactobacillus GG was effective in prevention of early atopic disease in children at high risk. Thus, gut microflora might be a hitherto unexplored source of natural immunomodulators and probiotics, for prevention of atopic disease.
Notes: Clinical Trial
Journal Article
Randomized Controlled Trial
Author Address: Department of Paediatrics, University of Turku and Turku University Hospital, Finland.

Title: Healthy Gut Microflora and Allergy: Factors Influencing Development of the Microbiota
Author: Kirjavainen, P. V.; Gibson, G. R.; (Date: Aug, 1999)
Journal: Ann Med; V. 31; Issue: 4; Pages: 288-92

Abstract: In humans, microbial colonization of the intestine begins just after birth. However, development of the normal flora is a gradual process, which is initially determined by factors such as composition of the maternal gut microflora, environment and possibly also by genetic aspects. A number of variables, such as the degree of hygiene, mode of delivery, use of antibiotics or other medication and a need for nursing in incubators, can all have a substantial effect on microbial colonization and development. Current knowledge on the significance and impact of such alterations on the health of the infant is poor. However, the essential role of the gut microflora in the development of the gut immune system indicates that a close relationship between allergic sensitization and the development of the intestinal microflora may occur in infancy. Intestinal micro-organisms could down-regulate the allergic inflammation by counterbalancing type 2 T-helper cell responses and by enhancing antigen exclusion through an immunoglobulin (Ig)A response. The efficacy of probiotics (microbial food additions) in the management of food allergy has been demonstrated, and these data suggest that also prebiotics, food components that target certain indigenous gut bacteria, can possibly be used for this purpose. In conclusion, the developmental pattern of the normal gut microbiota in allergic infants poses an important research avenue, as the role of the gut microflora in the mechanisms of allergy, and thereby the possible targets for efficient bacteriotherapy, are currently undetermined.
Notes: Journal Article
Review, Tutorial
Author Address: Department of Biochemistry and Food Chemistry, University of Turku, Finland.

Title: Probiotics and Prebiotics: Can Regulating the Activities of Intestinal Bacteria Benefit Health?
Author: Macfarlane, G. T.; Cummings, J. H.; (Date: Apr 10, 1999)
Journal: Bmj; V. 318; Issue: 7189; Pages: 999-1003

Notes: Journal Article
Review, Tutorial
Author Address: Medical Research Council Dunn Clinical Nutrition Centre, Cambridge CB2 2DH.

Title: Modulating Immune Responses with Probiotic Bacteria
Author: Matsuzaki, T.; Chin, J.; (Date: Feb, 2000)
Journal: Immunol Cell Biol; V. 78; Issue: 1; Pages: 67-73

Abstract: For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria.
Notes: Journal Article
Author Address: Yakult Central Institute for Microbiological Research, Kunitachi-shi, Tokyo, Japan.

Title: Bacterial Growth: Constant Obsession with Dn/Dt
Author: Neidhardt, F. C.; (Date: Dec, 1999)
Journal: J Bacteriol; V. 181; Issue: 24; Pages: 7405-8

Notes: Journal Article
Review, Tutorial
Author Address: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan 48109-0620, USA.

Title: Probiotics
Author: O’Sullivan, G. C.; (Date: Feb, 2001)
Journal: Br J Surg; V. 88; Issue: 2; Pages: 161-2

Notes: Journal Article
Author Address: Department of Surgery, Mercy Hospital, Cork, Ireland.

Title: Factors Controlling the Bacterial Colonization of the Intestine in Breastfed Infants
Author: Orrhage, K.; Nord, C. E.; (Date: Aug, 1999)
Journal: Acta Paediatr Suppl; V. 88; Issue: 430; Pages: 47-57

Abstract: This article summarizes the published data on the intestinal microflora in breastfed infants published during the last 15 y. Enterobacteria and enterococci are found in high numbers in most infants during the first week of life. Bifidobacteria and Bacteroides spp. are found in increasing numbers at the following weeks. The intestinal microflora in breastfed infants can also be followed by different biochemical parameters. Acetic acid is found in higher concentrations in breastfed than in formula-fed infants. Degradation of mucin starts later in breastfed than in formula-fed infants. The conversion of cholesterol to coprostanol is also delayed by breastfeeding. Geographical differences in the composition of the intestinal microflora in infants have been reported, i.e. enterobacteria, enterococci, bifidobacteria, lactobacilli and bacteroides show different occurrences in developed and developing countries. There are minor differences in the infant’s intestinal microflora due to breastfeeding or/and formula feeding.
Notes: Journal Article
Review, Tutorial
Author Address: Department of Immunology, Microbiology, Pathology and Infectious Diseases, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.

Title: Intestinal Microflora of Estonian and Swedish Infants
Author: Sepp, E.; Julge, K.; Vasar, M.; Naaber, P.; Bjorksten, B.; Mikelsaar, M.; (Date: Sep, 1997)
Journal: Acta Paediatr; V. 86; Issue: 9; Pages: 956-61

Abstract: The intestinal microflora of 1-y-old healthy Estonian (n = 27) and Swedish infants (n = 29) was studied by quantitative culture of faecal samples. The major differences were high counts of lactobacilli and eubacteria in the former and increased numbers of clostridia in the latter babies. Bifidobacteria and anaerobic cocci prevailed equally in both groups, while eubacteria and enterococci were the major microorganisms in many Estonian infants and bacteroides and clostridia in many Swedish infants. The microflora of the Estonian infants was in many aspects similar to the flora prevailing in infants of western Europe in the 1960s. The results suggest a shift in the intestinal microflora among infants in western industrialized countries.
Notes: Journal Article
Author Address: Department of Microbiology, University of Tartu, Estonia.

Title: Does Probiotics Administration Decrease Serum Endotoxin Levels in Infants?
Author: Urao, M.; Fujimoto, T.; Lane, G. J.; Seo, G.; Miyano, T.; (Date: Feb, 1999)
Journal: J Pediatr Surg; V. 34; Issue: 2; Pages: 273-6

Abstract: PURPOSE: The aim of this study was to examine whether administration of probiotics to infants can change the ratio of intestinal flora and thereby decrease serum endotoxin produced by potentially pathogenic microorganisms. METHODS: Nine infants including five with of biliary atresia, two with omphalocele, one each with Hirschsprung’s disease and imperforate anus were studied. All patients were stable, and no antibiotics were given during this study. A probiotic mixture consisting of Streptococcus faecalis, Clostridium butyricum and Bacillus mesentericus was administered orally to each infant at 2 g/day for 2 weeks. Fecal aerobic and anaerobic bacterial cultures, serum endotoxin level, and other biochemical parameters were examined. RESULTS: In fecal cultures, anaerobic bacteria including Bifidobacterium increased significantly whereas Escherichia coli, Streptococcus, and Klebsiella tended to decrease. The ratio of anaerobic to aerobic bacteria increased five times as a result of administration of probiotics, and serum endotoxin levels decreased. CONCLUSIONS: Probiotics affect intestinal bacterial flora by increasing anaerobic bacteria and decreasing the population of potentially pathogenic microorganisms. A decrease in luminal endotoxin may result in less endotoxin translocation or bacterial translocation.
Notes: Journal Article
Author Address: Department of Pediatric Surgery, Juntendo University School of Medicine, Tokyo, Japan.

Title: Role of Nutrients and Bacterial Colonization in the Development of Intestinal Host Defense
Author: Walker, W. A.; 2000)
Journal: J Pediatr Gastroenterol Nutr; V. 30 Suppl 2; Pages: S2-7

Abstract: In this introduction to the supplement on the use of pre- and probiotics in the health and disease of pediatric patients, I have summarized factors affecting the initial colonization of the neonatal intestine. The term bacterial-epithelial cross-talk was defined, and examples of the enterocyte response to both pathologic and indigenous flora stimulation illustrated. Immaturities in the human neonatal intestinal response to bacteria and their toxins were reviewed in the context of the pathogenesis of age-specific, bacterial gastrointestinal infectious diseases. Finally, the importance of pre- and probiotics as measures to strengthen the neonate’s intestinal host defenses in the prevention and treatment of specific age-related disease were considered.
Notes: Journal Article
Review, Tutorial
Author Address: Division of Nutrition, Harvard Medical School, Combined Program in Pediatric Gastroenterology and Nutrition, Children’s Hospital, Boston, Massachusetts 02115, USA.

Title: Bacterial Infection Induces Nitric Oxide Synthase in Human Neutrophils
Author: Wheeler, M. A.; Smith, S. D.; Garcia-Cardena, G.; Nathan, C. F.; Weiss, R. M.; Sessa, W. C.; (Date: Jan 1, 1997)
Journal: J Clin Invest; V. 99; Issue: 1; Pages: 110-6

Abstract: The identification of human inflammatory cells that express inducible nitric oxide synthase and the clarification of the role of inducible nitric oxide synthase in human infectious or inflammatory processes have been elusive. In neutrophil-enriched fractions from urine, we demonstrate a 43-fold increase in nitric oxide synthase activity in patients with urinary tract infections compared with that in neutrophil-enriched fractions from noninfected controls. Partially purified inducible nitric oxide synthase is primarily membrane associated, calcium independent, and inhibited by arginine analogues with a rank order consistent with that of purified human inducible nitric oxide synthase. Molecular, biochemical, and immunocytochemical evidence unequivocally identifies inducible nitric oxide synthase as the major nitric oxide synthase isoform found in neutrophils isolated from urine during urinary tract infections. Elevated inducible nitric oxide synthase activity and elevated nitric oxide synthase protein measured in patients with urinary tract infections and treated with antibiotics does not decrease until 6-10 d of antibiotic treatment. The extended elevation of neutrophil inducible nitric oxide synthase during urinary tract infections may have both antimicrobial and proinflammatory functions.
Notes: Journal Article
Author Address: Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

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