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Shirajum Monira,
Shota Nakamura,
Kazuyoshi Gotoh,
Kaori Izutsu,
Haruo Watanabe, Nur Haque Alam,
Takaaki Nakaya,
Toshihiro Horii,
Sk Imran Ali,
Tetsuya Iida,
Munirul Alam
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ABSTRACT: BACKGROUND: The diverse bacterial communities colonizing the gut (gastrointestinal tract) of infants as commensal flora, which play an important role in nutrient absorption and determining the state of health, are known to alter due to diarrhea. METHOD: Bacterial community dynamics in children suffering from cholera and during recovery period were examined in the present study by employing metagenomic tool, followed by DNA sequencing and analysis. For this, bacterial community DNA was extracted from fecal samples of nine clinically confirmed cholera children (age 2--3 years) at day 0 (acute cholera), day 2 (antibiotic therapy), day 7 and, and day 28, and the variable region of 16S rRNA genes were amplified by universal primer PCR. RESULTS: 454 parallel sequencing of the amplified DNA followed by similarity search of the sequenced data against an rRNA database allowed us to identify V. cholerae, the cause of cholera, in all nine children at day 0, and as predominant species in six children, accounting for 35% of the total gut microbiota on an average in all the nine children. The relative abundance (mean +/- sem %) of bacteria belonging to phyla Proteobacteria, Firmicutes, Bacteroidetes, and Actinobacteria, was 55 +/- 7, 18 +/- 4, 13 +/- 4, and 8 +/- 4, respectively, at day 0, while these values were 12 +/- 4, 43 +/- 4, 33 +/- 3, and 12 +/- 2, respectively, at day 28. As antibiotic therapy began, V. cholerae count declined significantly (p< 0.001) and was found only in four children at day 2 and two children at day 7 with the relative abundance of 3.7% and 0.01%, respectively, which continued up to day 28 in the two children. Compared to acute cholera condition (day 0), the relative abundance of Escherichia coli, Enterococcus, and Veillonella increased at day 2 (antibiotic therapy) while Bifidobacterium, Bacteroides, and Ruminococcus decreased. CONCLUSION: Cholera results expulsion of major commensal bacteria of phyla Bacteroidetes, Firmicutes, and Actinobacteria, and increase of harmful Proteobacteria to colonize the gut during acute and convalescence states. The observed microbiota disruption might explain the prevalent malnutrition in children of Bangladesh where diarrheal diseases are endemic.
Gut Pathogens 02/2013; 5(1):1. · 2.11 Impact Factor
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ABSTRACT: The human gut microbiota play a vital role in health and nutrition but are greatly modified during severe diarrhoea due to purging and pathogenic colonization. To understand the extent of loss during and after diarrhoea, faecal samples collected from children (n = 21) suffering from acute diarrhoea and from their healthy siblings (n = 9) were analyzed by 16S rRNA gene-targeted universal primer polymerase chain reaction (PCR), followed by temporal temperature gradient gel electrophoresis (TTGE). The gut microbiota decreased significantly as indicated by the number of TTGE bands at day 0 of acute diarrhoea [patients vs healthy siblings: 11 +/- 0.9 vs 21.8 +/- 1.1 (mean +/- standard error), p < 0.01]. The number of bands showed a steady increase from day 1 to day 7; however, it remained significantly less than that in healthy siblings (15 +/- 0.9, p < 0.01). These results suggest that appropriate therapeutic and post-diarrhoeal nutritional intervention might be beneficial for the early microbial restoration and recovery.
Journal of Health Population and Nutrition 09/2012; 30(3):250-6. · 0.95 Impact Factor
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Shirajum Monira,
Shota Nakamura,
Kazuyoshi Gotoh,
Kaori Izutsu,
Haruo Watanabe, Nur Haque Alam,
Hubert Ph Endtz,
Alejandro Cravioto,
Sk Imran Ali,
Takaaki Nakaya,
Toshihiro Horii,
Tetsuya Iida,
Munirul Alam
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ABSTRACT: Poor health and malnutrition in preschool children are longstanding problems in Bangladesh. Gut microbiota plays a tremendous role in nutrient absorption and determining the state of health. In this study, metagenomic tool was employed to assess the gut microbiota composition of healthy and malnourished children. DNA was extracted from fecal samples of seven healthy and seven malnourished children (n = 14; age 2-3 years) were analyzed for the variable region of 16S rRNA genes by universal primer PCR followed by high-throughput 454 parallel sequencing to identify the bacterial phyla and genera. Our results reveal that the healthy children had a significantly higher number of operational taxonomic unit in their gut than that of the malnourished children (healthy vs. malnourished: 546 vs. 310). In malnourished children, bacterial population of the phyla Proteobacteria and Bacteroidetes accounted for 46 and 18%, respectively. Conversely, in healthy children, Proteobacteria and Bacteroidetes accounted for 5% and 44, respectively (p < 0.001). In malnourished children, the phylum Proteobacteria included pathogenic genera, namely Klebsiella and Escherichia, which were 174-fold and 9-fold higher, respectively, than their healthy counterpart. The predominance of potentially pathogenic Proteobacteria and minimal level of Bacteroidetes as commensal microbiota might be associated to the ill health of malnourished children in Bangladesh.
Frontiers in microbiology. 01/2011; 2:228.
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09/2010; , ISBN: 978-953-307-120-6
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Cynthia L Sears,
Salequl Islam,
Amit Saha,
Maleka Arjumand, Nur Haque Alam,
A S G Faruque,
M A Salam,
Jai Shin,
David Hecht,
Andrej Weintraub,
R Bradley Sack,
Firdausi Qadri
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ABSTRACT: Diarrheal illnesses remain a leading cause of morbidity and mortality globally, with increasing recognition of long-term sequelae, including postinfectious irritable bowel syndrome and growth faltering, as well as cognitive deficits in children. Identification of specific etiologic agents is often lacking. In vitro and in vivo data suggest that enterotoxigenic Bacteroides fragilis (ETBF) may contribute to the burden of colonic inflammatory diarrheal disease. The study goal was to investigate the pathogenesis of ETBF diarrheal illnesses.
We performed an observational study of children and adults with acute diarrheal illnesses in Dhaka, Bangladesh, from January 2004 through November 2005, to define the clinical presentation, intestinal inflammatory responses, and systemic and intestinal antibody responses to ETBF. Other enteric pathogens were also evaluated.
ETBF was identified to cause a clinical syndrome with marked abdominal pain and nonfebrile inflammatory diarrhea in both children (age, >1 year) and adults. Fecal leukocytes, lactoferrin, and proinflammatory cytokines (interleukin 8, tumor necrosis factor-alpha)-as well as B. fragilis toxin systemic antitoxin responses-increased rapidly in ETBF-infected patients. Evidence of intestinal inflammation often persisted for at least 3 weeks, despite antibiotic therapy.
ETBF infection is a newly recognized cause of inflammatory diarrhea in children and adults. Future studies are needed to evaluate the role of ETBF in persistent colonic inflammation and other morbid sequelae of acute diarrheal disease.
Clinical Infectious Diseases 10/2008; 47(6):797-803. · 9.15 Impact Factor
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ABSTRACT: Inflammatory diarrhoea (ID) resulting from Shigella, Salmonella, Campylobacter and Entamoeba histolytica requires specific diagnosis for therapy. Differentiation between ID and non-inflammatory diarrhoea (NID) is often not clinically possible. A faecal occult blood test (FOBT) correlates with faecal leucocytes. Lactoferrin indicates an inflammatory process as a marker for faecal leucocytes. We evaluated diagnostic values of lactoferrin latex agglutination test (LT) either alone or in combination with FOBT, correlating with stool microscopy and microbiology in differentiating ID from NID.
The study population constituted patients enrolled in 2% systematic sampling of patients under Diarrhoeal Disease Surveillance System of Dhaka Hospital, ICDDR,B.
Between July and November 2002, 594 patients were enrolled; evaluation of FOBT and LT were done in 448/594 (75%) patients from whom either a single enteropathogen (315/594, 53%) or no pathogen (133/594, 22%) were identified and 146 were excluded for multiple pathogens. Invasive and non-invasive pathogens were isolated from 24% and 76% of the patients. FOBT and LT were positive in 40% and 39% of the samples. The sensitivities, specificities, PPVs, NPVs, and accuracies of FOBT were 55, 63, 24, 87 and 62%, and LT were 52, 64, 23, 86 and 62%, respectively.
FOBT and LT are not useful in differentiating ID from NID in diarrhoeal patients in Dhaka, Bangladesh.
Digestion 02/2007; 76(3-4):256-61. · 2.05 Impact Factor
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Firdausi Qadri,
Muhammad Shamsul Alam,
Mitsuaki Nishibuchi,
Taufiqur Rahman, Nur Haque Alam,
Jobayer Chisti,
Seiichi Kondo,
Junichi Sugiyama,
Nurul Amin Bhuiyan,
Minnie M Mathan,
David A Sack,
G Balakrish Nair
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ABSTRACT: In patients with diarrhea caused by Vibrio parahaemolyticus, antibody-secreting cell responses to thermostable direct hemolysin (TDH), lipopolysaccharide (LPS), and whole-cell bacteria were seen. TDH- and LPS-specific responses were seen in serum samples, and immunoglobulin A antibody responses were observed in stool. Levels of C-reactive protein and nitric oxide metabolites increased in the systemic circulation at the onset of illness. Tumor necrosis factor-alpha and lactoferrin levels were high during the acute stage in mucosal secretions and in plasma, whereas interleukin-1beta levels were high only in mucosal secretions. Duodenal and rectal biopsy specimens obtained at the onset of illness showed an acute inflammatory response. The lamina propria showed edema, congestion of blood vessels, and hemorrhage, with an increase in levels of polymorphonuclear neutrophils and macrophages. Strains belonging to different serotypes exhibited varying resistance to killing by serum; the O8:K21 strain was most sensitive. Infection with V. parahaemolyticus results in B cell responses and an acute inflammatory response that is self-limiting.
The Journal of Infectious Diseases 05/2003; 187(7):1085-96. · 6.41 Impact Factor
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ABSTRACT: Investigations were carried out to study the production of factors associated with the innate immune response in the systemic and mucosal compartments in adults and children infected with Vibrio cholerae O1 and V. cholerae O139. The levels of nonspecific mediators of the innate defense system, i.e., prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)), and lactoferrin (Lf), as well as myeloperoxidase (MPO), were elevated at the acute stage of the disease in stools obtained from both O1- and O139-infected adults and children. In the systemic compartment, the levels of Lf were increased after onset of disease, which in children remained elevated up to convalescence compared to the healthy controls. Increased concentrations of C-reactive protein were seen in the sera of adult cholera patients at the acute stage of infection. Elevated levels of the nitric oxide (NO*) metabolites (nitrite and nitrate [NO(2)(-) and NO(3)(-)]) were detected in plasma but not in urine. The activity of the scavenger of reactive oxygen species, superoxide dismutase, was higher in the plasma of adults immediately after the onset of disease, suggesting that an active scavenging of reactive oxygen species was taking place. The concentration of 8-iso-prostaglandin F(2 alpha) remained unchanged in the systemic and mucosal compartments in the study subjects. After the recovery of patients from cholera, the concentration of the majority of the metabolites decreased to baseline levels by day 30 after the onset of infection. Immunohistochemical staining showed increased tissue expression of MPO, Lf, and inducible nitric oxide synthase at the acute stage in the duodenal biopsies of adults and rectal biopsies obtained from children with cholera. Very little difference was seen in the levels of the different inflammatory mediators in patients infected with V. cholerae O1 or the encapsulated V. cholerae O139. In summary, these results suggest that elevated concentrations of Lf, MPO, PGE(2), LTB(4), and NO*, as well as other metabolites, during the acute stage of the disease indicate that the innate defense system, as well as the inflammatory process, is activated in both adults and pediatric patients infected with V. cholerae O1 and O139.
Clinical and Diagnostic Laboratory Immunology 04/2002; 9(2):221-9. · 2.51 Impact Factor
