T R Klaenhammer

North Carolina State University, Raleigh, NC, United States

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Publications (257)838.02 Total impact

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    ABSTRACT: Commercial probiotic strains for food or supplement use can be altered in different ways for a variety of purposes. Production conditions for the strain or final product may be changed to address probiotic yield, functionality, or stability. Final food products may be modified to improve flavor and other sensory properties, provide new product formats, or respond to market opportunities. Such changes can alter the expression of physiological traits owing to the live nature of probiotics. In addition, genetic approaches may be used to improve strain attributes. This review explores whether genetic or phenotypic changes, by accident or design, might affect the efficacy or safety of commercial probiotics. We highlight key issues important to determining the need to re-confirm efficacy or safety after strain improvement, process optimization, or product formulation changes. Research pinpointing the mechanisms of action for probiotic function and the development of assays to measure them are greatly needed to better understand if such changes have a substantive impact on probiotic efficacy.
    Annals of the New York Academy of Sciences 02/2014; 1309(1):1-18. · 4.38 Impact Factor
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    ABSTRACT: Lactose intolerance (LI) is a common medical problem with limited treatment options. The primary symptoms are abdominal pain, diarrhea, bloating, flatulence, and cramping. Limiting dairy foods to reduce symptoms contributes to low calcium intake and the risk for chronic disease. Adaptation of the colon bacteria to effectively metabolize lactose is a novel and potentially useful approach to improve lactose digestion and tolerance. RP-G28 is a proprietary GOS mixture being investigated to improve lactose digestion and the symptoms of lactose intolerance in affected patients. A randomized, double-blind, parallel group, placebo-controlled study was conducted at 2 sites in the United States. RP-G28 or placebo was administered to 85 patients with LI for 35 days. Post-treatment, subjects reintroduced dairy into their daily diets and were followed for 30 additional days to evaluate lactose digestion as measured by hydrogen production and symptom improvements via a patient-reported symptom assessment instrument. Lactose digestion and symptoms of LI trended toward improvement on RP-G28 at the end of treatment and 30 days post-treatment. A reduction in abdominal pain was also demonstrated in the study results. Fifty percent of RP-G28 subjects with abdominal pain at baseline were free from pain at the end of treatment and 30 days post treatment (p = 0.0190). RP-G28 subjects were also six times more likely to claim lactose tolerance post-treatment once dairy foods had been re-introduced into their diets (p = 0.0389). Efficacy trends and favorable safety/tolerability findings suggest that RP-G28 appears to be a potentially useful approach for improving lactose digestion and LI symptoms. The concurrent reduction in abdominal pain and improved overall tolerance could be a meaningful benefit to lactose intolerant individuals.Study registration: ClinicalTrials.gov NCT01113619.
    Nutrition Journal 12/2013; 12(1):160. · 2.65 Impact Factor
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    ABSTRACT: Recent advances in our understanding of the community structure and function of the human microbiome have implications for the potential role of probiotics and prebiotics in promoting human health. A group of experts recently met to review the latest advances in microbiota/microbiome research and discuss the implications for development of probiotics and prebiotics, primarily as they relate to effects mediated via the intestine. The goals of the meeting were to share recent advances in research on the microbiota, microbiome, probiotics, and prebiotics, and to discuss these findings in the contexts of regulatory barriers, evolving healthcare environments, and potential effects on a variety of health topics, including the development of obesity and diabetes; the long-term consequences of exposure to antibiotics early in life to the gastrointestinal (GI) microbiota; lactose intolerance; and the relationship between the GI microbiota and the central nervous system, with implications for depression, cognition, satiety, and mental health for people living in developed and developing countries. This report provides an overview of these discussions.
    Annals of the New York Academy of Sciences 11/2013; · 4.38 Impact Factor
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    ABSTRACT: Bacterial surface (S-) layers are crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (Slps), with molecular masses ranging from 40 to 200 kDa. The S-layer forming bacterium, Lactobacillus acidophilus NCFM expresses three major surface layer proteins: SlpA (46 kDa), SlpB (47 kDa) and SlpX (51 kDa). SlpA has a demonstrated role in adhesion to Caco-2 intestinal epithelial cells in vitro, and has been shown to modulate dendritic cell (DC) and T-cell functionalities with murine DCs. In this study, a modification of a standard lithium chloride (LiCl) S-layer extraction revealed 37 proteins were solubilized from the S-layer wash fraction. Of these, 30 have predicted cleavage sites for secretion; 24 are predicted to be extracellular; 6 are lipid-anchored; 3 have N-terminal hydrophobic membrane spanning regions; and 4 are intracellular, potentially moonlighting proteins. Some of these proteins, designated Surface-Layer Associated Proteins (SLAPs), may be loosely associated with or embedded within the bacterial S-layer complex. Lba-1029, a putative SLAP, was deleted from the chromosome of L. acidophilus. Phenotypic characterization of the deletion mutant demonstrated that the SLAP LBA1029 contributes to a pro-inflammatory TNF-α response from murine DCs. This study identified novel extracellular proteins and putative SLAPs of L. acidophilus NCFM using liquid chromatography-tandem mass spectrometry (LC-MS/MS). SLAPs appear to impart important surface display features and immunological properties to microbes that are coated by S-layers.
    Microbiology 09/2013; · 3.06 Impact Factor
  • Yong Jun Goh, Todd R Klaenhammer
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    ABSTRACT: Glycogen metabolism contributes to energy storage and various physiological functions in some prokaryotes, including colonization persistence. A role for glycogen metabolism is proposed on the survival and fitness of L. acidophilus, a probiotic microbe, in the human gastrointestinal environment. L. acidophilus NCFM possesses a glycogen metabolism (glg) operon consisting of glgBCDAP-amy-pgm genes. Expression of the glg operon and glycogen accumulation were carbon source- and growth phase-dependent, and were repressed by glucose. The highest intracellular glycogen content was observed in early-log phase cells grown on trehalose, which was followed by a drastic decrease of glycogen content prior to entering stationary phase. In raffinose-grown cells, however, glycogen accumulation gradually declined following early-log phase and was maintained at stable levels throughout stationary phase. Raffinose also induced an overall higher temporal glg expression throughout growth compared to trehalose. Isogenic ΔglgA (glycogen synthase) and ΔglgB (glycogen-branching enzyme) mutants are glycogen-deficient and exhibited growth defects on raffinose. The latter observation suggests a reciprocal relationship between glycogen synthesis and raffinose metabolism. Deletion of glgB or glgP (glycogen phosphorylase) resulted in defective growth and increased bile sensitivity. The data indicates that glycogen metabolism is involved in growth maintenance, bile tolerance and complex carbohydrate utilization in L. acidophilus.
    Molecular Microbiology 07/2013; · 4.96 Impact Factor
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    ABSTRACT: BACKGROUND: Probiotic bifidobacteria in combination with prebiotic carbohydrates have documented positive effects on human health regarding gastrointestinal disorders and improved immunity, however the selective routes of uptake remain unknown for most candidate prebiotics. The differential transcriptomes of Bifidobacterium animalis subsp. lactis Bl-04, induced by 11 potential prebiotic oligosaccharides were analyzed to identify the genetic loci involved in the uptake and catabolism of alpha- and beta-linked hexoses, and beta-xylosides. RESULTS: The overall transcriptome was modulated dependent on the type of glycoside (galactosides, glucosides or xylosides) utilized. Carbohydrate transporters of the major facilitator superfamily (induced by gentiobiose and beta-galacto-oligosaccharides (GOS)) and ATP-binding cassette (ABC) transporters (upregulated by cellobiose, GOS, isomaltose, maltotriose, melibiose, panose, raffinose, stachyose, xylobiose and beta-xylo-oligosaccharides) were differentially upregulated, together with glycoside hydrolases from families 1, 2, 13, 36, 42, 43 and 77. Sequence analysis of the identified solute-binding proteins that determine the specificity of ABC transporters revealed similarities in the breadth and selectivity of prebiotic utilization by bifidobacteria. CONCLUSION: This study identified the differential gene expression for utilization of potential prebiotics highlighting the extensive capabilities of Bifidobacterium lactis Bl-04 to utilize oligosaccharides. Results provide insights into the ability of this probiotic microbe to utilize indigestible carbohydrates in the human gastrointestinal tract.
    BMC Genomics 05/2013; 14(1):312. · 4.40 Impact Factor
  • Kurt Selle, Todd R Klaenhammer
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    ABSTRACT: Certain lactic acid bacteria have the capacity to occupy mucosal niches of humans, including the oral cavity, gastrointestinal tract, and vagina. Among commensal lactic acid bacteria are the species of the acidophilus complex, which have proven to be a substantial reservoir for microorganisms with probiotic attributes. Specifically, Lactobacillus gasseri is an autochthonous microorganism which has been evaluated for probiotic activity based on the availability of genome sequence and species-specific adaptation to the human mucosa. Niche-related characteristics of L. gasseri contributing to indigenous colonization include tolerance of low pH environments, resistance to bile salts, and adhesion to the host epithelium. In humans L. gasseri elicits various health benefits through its antimicrobial activity, bacteriocin production, and immunomodulation of the innate and adaptive systems. The genomic and empirical evidence supporting use of L. gasseri in probiotic applications is substantiated by clinical trial data displaying maintenance of vaginal homeostasis, mitigation of Helicobacter pylori infection, and amelioration of diarrhea. © 2013 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
    FEMS microbiology reviews 03/2013; · 10.96 Impact Factor
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    ABSTRACT: The authors sincerely regret the following omissions from the research paper "Lactic acid production by Streptococcus thermophilus alters Clostridium difficile infection and in vitro Toxin A production" published in the November/December 2013 issue of Gut Microbes. ( 1) Michael P. Timko should have been listed as the sixth co-author as follows:: Kolling GL, ( 1) Wu M, ( 2) Warren CA, ( 1) Durmaz E, ( 3) Klaenhammer TR, ( 3) Timko MP, ( 2) Guerrant RL. ( 1) : ( 1) Department of Internal Medicine/Division of Infectious Diseases; University of Virginia; Charlottesville, VA USA; ( 2) Department of Biology; University of Virginia; Charlottesville, VA USA; ( 3) Department of Food, Bioprocessing and Nutrition Sciences; North Carolina State University; Raleigh, NC USA. : The Acknowledgments section should also read: This research was supported by a Young Investigator Grant in Probiotics Research (to G.L.K.) from the Global Probiotics Council, the National Institutes of Health Grant U01AI075526 (to R.L.G.), the Hartwell Foundation (to M.P.T. and G.L.K.) and the North Carolina Agricultural Foundation (to E.D. and T.R.K.). The authors thank Pascal Hols for kindly providing the bacteriocin negative mutant of S. thermophilus for use as a control in this study. The authors wish to thank Dr Relana Pinkerton for assistance with a portion of the statistical analysis.
    Gut Microbes 03/2013; 4(2):175.
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    Emma K Call, Todd R Klaenhammer
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    ABSTRACT: Lactic acid bacteria (LAB) are a diverse group of Gram-positive bacteria found in a vast array of environments including dairy products and the human gastrointestinal tract (GIT). In both niches, surface proteins play a crucial role in mediating interactions with the surrounding environment. The sortase enzyme is responsible for covalently coupling a subset of sortase-dependent proteins (SDPs) to the cell wall of Gram-positive organisms through recognition of a conserved C-terminal LPXTG motif. Genomic sequencing of LAB and annotation has allowed for the identification of sortase and SDPs. Historically, sortase and SDPs were predominately investigated for their role in mediating pathogenesis. Identification of these proteins in LAB has shed light on their important roles in mediating nutrient acquisition through proteinase P as well as positive probiotic attributes including adhesion, mucus barrier function, and immune signaling. Furthermore, sortase expression signals in LAB have been exploited as a means to develop oral vaccines targeted to the GIT. In this review, we examine the collection of studies which evaluate sortase and SDPs in select species of dairy-associated and health promoting LAB.
    Frontiers in Microbiology 01/2013; 4:73.
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    ABSTRACT: There has been continued and expanding recognition of probiotic approaches for treating gastrointestinal and systemic disease, as well as increased acceptance of probiotic therapies by both the public and the medical community. A parallel development has been the increasing recognition of the diverse roles that the normal gut microbiota plays in the normal biology of the host. This advance has in turn has been fed by implementation of novel investigative technologies and conceptual paradigms focused on understanding the fundamental role of the microbiota and indeed all commensal bacteria, on known and previously unsuspected aspects of host physiology in health and disease. This review discuses current advances in the study of the host-microbiota interaction, especially as it relates to potential mechanisms of probiotics. It is hoped these new approaches will allow more rational selection and validation of probiotic usage in a variety of clinical conditions.
    Gut Microbes 12/2012; 4(2).
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    ABSTRACT: Antibiotic treatment to treat specific infections has the potential to effectively target the offending microbe as well as other microbes that colonize sites within a host. Antibiotic-associated diarrhea (AAD) is a classic example resulting from disruption of host microbial communities; 20% of patients with AAD are likely to become colonized with Clostridium difficile. Restoration of a "normal" microbial community within the host using probiotic bacteria is one approach to circumvent AAD and C. difficile infection. The goals of this study were to assess the interactions between Streptococcus thermophilus, a potential probiotic organism and C. difficile using both in vitro and in vivo systems. Exposure of C. difficile to filtered supernatants from S. thermophilus showed a dose-dependent, bactericidal effect due to lactic acid. Additional studies show that levels of lactic acid (10 mM) that did not inhibit bacterial growth had the potential to decrease tcdA expression and TcdA release into the extracellular milieu. In vivo, treatment with viable S. thermophilus significantly increased luminal levels of lactate in the cecum compared with UV-irradiated S. thermophilus. In the context of infection with C. difficile, mice treated with viable S. thermophilus exhibited 46% less weight loss compared with untreated controls; moreover, less pathology, diarrhea, and lower detectable toxin levels in cecal contents were evident more often in S. thermophillus treated mice. A significant, inverse correlation (Spearman r = -0.942, p = 0.017) between the levels of luminal lactate and abundance of C. difficile were noted suggesting that lactate produced by S. thermophilus is a factor impacting the progression of C. difficile infection in the murine system.
    Gut Microbes 11/2012; 3(6).
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    ABSTRACT: Oral vaccines that elicit a mucosal immune response may be effective against human immunodeficiency virus type 1 (HIV-1) because its transmission occurs mainly at the mucosa. The aim of this study was to construct recombinant Lactobacillus for oral delivery of oral vaccines against HIV-1 and to evaluate their immunogenicity. A recombinant Lactobacillus acidophilus strain expressing the HIV-1 Gag on the bacterial cell surface was established by fusion with the signal peptide and anchor motif of a mucus binding protein (Mub) from L. acidophilus with or without coexpression of Salmonella enterica serovar Typhimurium flagellin (FliC) fused to a different Mub signal peptide and anchor. Using HEK293 cells engineered to express Toll-like receptor 5 (TLR5), the biological activity of FliC on the bacterial cell surfaces was determined. The surface-exposed flagellin retained its TLR5-stimulating activity, suggesting that the recombinant strain with Gag and FliC dual display might provide a different immunopotency than the strain expressing only Gag. The immunological properties of the recombinant strains were assessed by coculture with human myeloid dendritic cells (DCs). The heterologous antigens on the cell surface affected maturation and cytokine responses of DCs. Acquired immune responses were also investigated by intragastric immunization of mice. The enzyme-linked immunosorbent spot assay showed induction of gamma interferon-producing cells at local mucosa after immunization of mice with the Gag-producing strain. Meanwhile, the immunization with L. acidophilus displaying both Gag and FliC resulted in an increase of Gag-specific IgA-secreting cells. These results suggested that the Gag-displaying L. acidophilus elicited specific immune responses and the coexistence of FliC conferred an adjuvant effect on local IgA production.
    Clinical and vaccine Immunology: CVI 07/2012; 19(9):1374-81. · 2.60 Impact Factor
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    ABSTRACT: An imbalance of commensal bacteria and their gene products underlies mucosal and, in particular, gastrointestinal inflammation and a predisposition to cancer. Lactobacillus species have received considerable attention as examples of beneficial microbiota. We have reported previously that deletion of the phosphoglycerol transferase gene that is responsible for lipoteichoic acid (LTA) biosynthesis in Lactobacillus acidophilus (NCK2025) rendered this bacterium able to significantly protect mice against induced colitis when delivered orally. Here we report that oral treatment with LTA-deficient NCK2025 normalizes innate and adaptive pathogenic immune responses and causes regression of established colonic polyps. This study reveals the proinflammatory role of LTA and the ability of LTA-deficient L. acidophilus to regulate inflammation and protect against colonic polyposis in a unique mouse model.
    Proceedings of the National Academy of Sciences 06/2012; 109(26):10462-7. · 9.74 Impact Factor
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    Sarah O'Flaherty, Todd R Klaenhammer
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    ABSTRACT: Analysis of global temporal gene expression by human intestinal cells when exposed to Lactobacillus acidophilus revealed induction of immune-related pathways and NF-κB target genes after a 1-h exposure, compared to a 4- or 8-h exposure. Additionally, an L. acidophilus derivative expressing covalently bound flagellin resulted in increased induction of il8, cxc1, and cxcl2 compared to the parent L. acidophilus.
    Applied and environmental microbiology 05/2012; 78(14):5028-32. · 3.69 Impact Factor
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    ABSTRACT: The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo. To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s) of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus surface layer protein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031). Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56), and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction. These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.
    Journal of Inflammation 03/2012; 9:7. · 2.55 Impact Factor
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    ABSTRACT: To investigate the mechanism(s) by which the intestinal commensal microbe Lactobacillus acidophilus can affect host immunity, we studied the role of a component of the cell wall, lipoteichoic acid, in colitis. Colitis was induced by the intraperitoneal injection of pathogenic CD4(+)CD25(-)CD45RB(hi) T cells into Rag1(-/-) mice. The parental strain, NCK56, or the lipoteichoic acid-deficient strain, NCK2025, was then administered orally. Fluorescent microscopy was employed to examine resulting cell populations and their cytokine production in the colon. NCK2025 enhanced IL-10 production by dendritic cells and macrophages. Increased numbers of regulatory dendritic cells coincided with the induction of activated FoxP3(+) Tregs. These results suggest that the oral administration of the genetically modified strain NCK2025 may be an effective immunotherapeutic approach that reprograms the immune response in colonic inflammatory conditions.
    Immunotherapy 02/2012; 4(2):151-61. · 2.39 Impact Factor
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    ABSTRACT: The potential health benefits of probiotic bacteria have led to the isolation of new microbial strains for incorporation into food products. However, newly isolated candidate probiotic organisms do not automatically share the "generally recognized as safe" (GRAS) status of traditional lactic acid bacteria (LAB). Before their introduction into food products, the safety of new isolates has to be evaluated. The objective of this study was to characterize LAB isolates from the stool of a newborn infant, and evaluate their safety and probiotic potential, in vitro. Thirty colonies were identified as Lactobacillus gasseri through sequencing of 16S rDNA. Pulsed Field Gel Electrophoresis using restriction enzymes SmaI and Apa I revealed that 29 of the L. gasseri were nearly identical, however one isolate exhibited a distinctive DNA fingerprint. All 30 L. gasseri were evaluated for resistance to antibiotics, bile tolerance, hemolytic activity and antagonism toward selected pathogens. All 30 strains harbored three plasmids, with one strain that showed strong tolerance to 0.5% of bile and harbored a unique fourth plasmid encoding a putative multidrug resistance transporter protein (LmrB). No hemolytic activity or antagonism, beyond acid inhibition was observed. Three selected strains UFVCC1083, 1091 and 1112 showed strong resistance to simulated small intestinal and gastric juices and adhered in vitro to mucin and two intestinal epithelial cell lines, Caco-2 and HT-29. This study identified and characterized recently isolated L. gasseri strains from faeces of a breast fed infant as potential probiotic candidates for use in the human milk banks in Brazil.
    Gut Microbes 01/2012; 3(1):15-24.
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    ABSTRACT: The human gastrointestinal tract can be positively modulated by dietary supplementation of probiotic bacteria in combination with prebiotic carbohydrates. Here differential transcriptomics and functional genomics were used to identify genes in Lactobacillus acidophilus NCFM involved in the uptake and catabolism of 11 potential prebiotic compounds consisting of α- and β- linked galactosides and glucosides. These oligosaccharides induced genes encoding phosphoenolpyruvate-dependent sugar phosphotransferase systems (PTS), galactoside pentose hexuronide (GPH) permease, and ATP-binding cassette (ABC) transporters. PTS systems were upregulated primarily by di- and tri-saccharides such as cellobiose, isomaltose, isomaltulose, panose and gentiobiose, while ABC transporters were upregulated by raffinose, Polydextrose, and stachyose. A single GPH transporter was induced by lactitol and galactooligosaccharides (GOS). The various transporters were associated with a number of glycoside hydrolases from families 1, 2, 4, 13, 32, 36, 42, and 65, involved in the catabolism of various α- and β-linked glucosides and galactosides. Further subfamily specialization was also observed for different PTS-associated GH1 6-phospho-β-glucosidases implicated in the catabolism of gentiobiose and cellobiose. These findings highlight the broad oligosaccharide metabolic repertoire of L. acidophilus NCFM and establish a platform for selection and screening of both probiotic bacteria and prebiotic compounds that may positively influence the gastrointestinal microbiota.
    PLoS ONE 01/2012; 7(9):e44409. · 3.73 Impact Factor
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    ABSTRACT: The handling and treatment of biological samples is critical when characterizing the composition of the intestinal microbiota between different ecological niches or diseases. Specifically, exposure of fecal samples to room temperature or long term storage in deep freezing conditions may alter the composition of the microbiota. Thus, we stored fecal samples at room temperature and monitored the stability of the microbiota over twenty four hours. We also investigated the stability of the microbiota in fecal samples during a six month storage period at -80°C. As the stability of the fecal microbiota may be affected by intestinal disease, we analyzed two healthy controls and two patients with irritable bowel syndrome (IBS). We used high-throughput pyrosequencing of the 16S rRNA gene to characterize the microbiota in fecal samples stored at room temperature or -80°C at six and seven time points, respectively. The composition of microbial communities in IBS patients and healthy controls were determined and compared using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline. The composition of the microbiota in fecal samples stored for different lengths of time at room temperature or -80°C clustered strongly based on the host each sample originated from. Our data demonstrates that fecal samples exposed to room or deep freezing temperatures for up to twenty four hours and six months, respectively, exhibit a microbial composition and diversity that shares more identity with its host of origin than any other sample.
    PLoS ONE 01/2012; 7(10):e46953. · 3.73 Impact Factor
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    ABSTRACT: Probiotic microbes rely on their ability to survive in the gastrointestinal tract, adhere to mucosal surfaces, and metabolize available energy sources from dietary compounds, including prebiotics. Genome sequencing projects have proposed models for understanding prebiotic catabolism, but mechanisms remain to be elucidated for many prebiotic substrates. Although β-galactooligosaccharides (GOS) are documented prebiotic compounds, little is known about their utilization by lactobacilli. This study aimed to identify genetic loci in Lactobacillus acidophilus NCFM responsible for the transport and catabolism of GOS. Whole-genome oligonucleotide microarrays were used to survey the differential global transcriptome during logarithmic growth of L. acidophilus NCFM using GOS or glucose as a sole source of carbohydrate. Within the 16.6-kbp gal-lac gene cluster, lacS, a galactoside-pentose-hexuronide permease-encoding gene, was up-regulated 5.1-fold in the presence of GOS. In addition, two β-galactosidases, LacA and LacLM, and enzymes in the Leloir pathway were also encoded by genes within this locus and up-regulated by GOS stimulation. Generation of a lacS-deficient mutant enabled phenotypic confirmation of the functional LacS permease not only for the utilization of lactose and GOS but also lactitol, suggesting a prominent role of LacS in the metabolism of a broad range of prebiotic β-galactosides, known to selectively modulate the beneficial gut microbiota.
    Proceedings of the National Academy of Sciences 10/2011; 108(43):17785-90. · 9.74 Impact Factor

Publication Stats

10k Citations
838.02 Total Impact Points


  • 1980–2013
    • North Carolina State University
      • • Department of Food, Bioprocessing and Nutrition Science
      • • Southeast Dairy Foods Research Center
      • • Department of Microbiology
      Raleigh, NC, United States
  • 2012
    • University of Florida
      • Department of Infectious Diseases and Pathology
      Gainesville, FL, United States
    • Universidade Federal de Ouro Preto
      Ouro Preto, Minas Gerais, Brazil
  • 2011–2012
    • Technical University of Denmark
      • Department of Systems Biology
      København, Capital Region, Denmark
  • 2009–2012
    • Northwestern University
      • • Feinberg School of Medicine
      • • Department of Medicine
      Evanston, IL, United States
  • 2010
    • AgResearch
      Hamilton City, Waikato, New Zealand
  • 2008
    • U.S. Army Medical Research Institute of Infectious Diseases
      Maryland, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2005
    • University of Reading
      Reading, England, United Kingdom
    • Duke University Medical Center
      Durham, North Carolina, United States
    • National Cancer Institute (USA)
      Maryland, United States
  • 2004–2005
    • California State Polytechnic University, Pomona
      Pomona, California, United States
  • 2003
    • Lawson Health Research Institute
      London, Ontario, Canada
  • 2002
    • Wageningen University
      Wageningen, Gelderland, Netherlands
  • 1994
    • University of Otago
      • Department of Microbiology and Immunology
      Dunedin, Otago, New Zealand
  • 1976–1993
    • University of Minnesota Duluth
      Duluth, Minnesota, United States