Alline R. Pacheco

Verve Therapeutics (United States)

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Vanessa Sperandio

The University of Texas Southwestern Medical Center

David A. Mills

University of California, Davis

Matthew K. Waldor

Brigham and Women's Hospital

Danielle G. Lemay

Western Human Nutrition Research Center

Brigid M. Davis

Harvard University

Carlos J. Blondel

Universidad Andrés Bello

Saumya Wickramasinghe

University of California, Davis

John G. Doench

Broad Institute

Bethany M. Henrick

University of Nebraska–Lincoln

Helen E. Raybould

University of California, Davis

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Harvard University

University of California, Davis

Brigham and Women's Hospital

The University of Texas Southwestern Medical Center

Southwestern Medical Center

Howard Hughes Medical Institute

University of California System

Verve Therapeutics (United States)

Universidade de São Paulo

Universidade Estadual de Campinas (UNICAMP)

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Additional file 1: of Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells

Figshare (2015)

Saumya Wickramasinghe Alline R. Pacheco Danielle G. Lemay David A. Mills

A Microsoft Excel file that contains spreadsheets of Caco-2 genes differentially expressed in response to B. infantis grown on GLU, LAC, or HMO. (XLSX 86 kb)

Caco-2

10.6084/m9.figshare.c.3643475_d2

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Citations (0)

Involvement of the Helicobacter pylori plasticity region and cag pathogenicity island genes in the development of gastroduodenal diseases

European Journal of Clinical Microbiology & Infectious Diseases (2008)

Alline R. Pacheco José Luiz Proença-Módena Ana Isabela L. Sales-Moioli Y. Fukuhara Wanderley Dias da Silveira

CagA

Pathogenicity island

Peptic

Medical microbiology

Spirillaceae

10.1007/s10096-008-0549-8

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Citations (32)

Endocannabinoids Inhibit the Induction of Virulence in Enteric Pathogens

Cell (2020)

Melissa Ellermann Alline R. Pacheco Angel G. Jimenez Regan M. Russell Santiago Cuesta

Gut–brain axis

10.1016/j.cell.2020.09.022

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Citations (43)

Bifidobacteria grown on human milk oligosaccharides downregulate the expression of inflammation-related genes in Caco-2 cells

BMC Microbiology (2015)

Saumya Wickramasinghe Alline R. Pacheco Danielle G. Lemay David A. Mills

Breastfed human infants are predominantly colonized by bifidobacteria that thrive on human milk oligosaccharides (HMO). Two predominant species of bifidobacteria in infant feces are Bifidobacterium breve (B. breve) and Bifidobacterium longum subsp. infantis (B. infantis), both of which include avid HMO-consumer strains. Our laboratory has previously shown that B. infantis, when grown on HMO, increases adhesion to intestinal cells and increases the expression of the anti-inflammatory cytokine interleukin-10. The purpose of the current study was to investigate the effects of carbon source—glucose, lactose, or HMO—on the ability of B. breve and B. infantis to adhere to and affect the transcription of intestinal epithelial cells on a genome-wide basis. HMO-grown B. infantis had higher percent binding to Caco-2 cell monolayers compared to B. infantis grown on glucose or lactose. B. breve had low adhesive ability regardless of carbon source. Despite differential binding ability, both HMO-grown strains significantly differentially affected the Caco-2 transcriptome compared to their glucose or lactose grown controls. HMO-grown B. breve and B. infantis both downregulated genes in Caco-2 cells associated with chemokine activity. The choice of carbon source affects the interaction of bifidobacteria with intestinal epithelial cells. HMO-grown bifidobacteria reduce markers of inflammation, compared to glucose or lactose-grown bifidobacteria. In the future, the design of preventative or therapeutic probiotic supplements may need to include appropriately chosen prebiotics.

Bifidobacterium breve

Bifidobacterium longum

Caco-2

10.1186/s12866-015-0508-3

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Citations (75)

Bifidobacterium grown on human milk oligosaccharides produce tryptophan metabolite Indole‐3‐lactic acid that significantly decreases inflammation in intestinal cells in vitro

The FASEB Journal (2018)

Amy M. Ehrlich Bethany M. Henrick Alline R. Pacheco Diana H. Taft Gege Xu

Bifidobacterium longum subsp. infantis ( B. infantis ) is a commensal bacterium that colonizes the infant gastrointestinal tract. This bacterium can efficiently utilize the abundant supply of oligosaccharides found in human milk (HMO) to help establish residence and generate bioactive metabolites which may produce beneficial effects by acting directly on the host. We hypothesized that metabolites from Bifidobacterium grown on human milk oligosaccharides would reduce inflammation in the intestine. To test this we first needed to identify metabolite candidates by growing B. infantis on either lactose or HMO and analyzing the metabolites produced using NMR spectroscopy. These metabolites were then compared to those found in Bifidobacterium ‐dominated infant fecal samples. Once specific metabolites were identified, we treated intestinal and macrophage cells grown in culture to test if they exhibited an anti‐inflammatory response during endotoxin challenge. Lastly, we sought to find which pathway might be activated. We found that B. infantis grown on HMO produced significantly greater quantities of the tryptophan metabolite indole‐3‐lactic acid (ILA). Significantly higher amounts of ILA were also found in fecal samples from a population of infants with high compared to low abundance of Bifidobacterium species. The direct effects of ILA were assessed in macrophage and intestinal epithelial cell lines. ILA (at concentrations from 1 to 10mM) significantly attenuated lipopolysaccharide (LPS)‐induced activation of NF‐kB in macrophages. Similarly, ILA significantly attenuated LPS‐induced increase in the pro‐inflammatory cytokine IL‐8. ILA acts through the aryl hydrogen receptor (AhR) in intestinal epithelial cells as shown through increased nuclear localization of the AhR as well as increased protein expression of the AhR targeted gene CYP1A1. Activation of the AhR has been shown to exert a multitude of beneficial effects on the host including promoting normal intestinal immune function. These findings suggest that ILA, a predominant metabolite from B. infantis , can protect the epithelium via activation of AhR This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Bifidobacterium longum

10.1096/fasebj.2018.32.1_supplement.lb359

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Citations (24)

The Impact of the Milk Glycobiome on the Neonate Gut Microbiota

Annual Review of Animal Biosciences (2014)

Alline R. Pacheco Daniela Barile Mark A. Underwood David A. Mills

Human milk is a complete source of nourishment for the infant. Exclusive breastfeeding not only sustains the infant's development but also guides the proliferation of a protective intestinal microbiota. Among the many components of milk that modulate the infant gut microbiota, the milk glycans, which comprise free oligosaccharides, glycoproteins, and glycolipids, are increasingly recognized as drivers of microbiota development and overall gut health. These glycans may display pleiotropic functions, conferring protection against infectious diseases and also acting as prebiotics, selecting for the growth of beneficial intestinal bacteria. The prebiotic effect of milk glycans has direct application to prevention of diseases such as necrotizing enterocolitis, a common and devastating disease of preterm infants. In this article, we review the impact of the human (and bovine) milk glycome on gut health through establishment of a milk-oriented microbiota in the neonate.

Prebiotic

Necrotizing Enterocolitis

Glycome

10.1146/annurev-animal-022114-111112

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Citations (168)

Implicação de genes da zona de plasticidade e da ilha de patogenicidade cag (PAIcag) de Helicobacter pylori no desenvolvimento de doenças gastroduodenais

Alline R. Pacheco Marcelo Brocchi

Helicobacter pylori e um bacilo Gram-negativo, espiralado, microaerofilo, e flagelado, incluido na familia Helicobacteraceae. Essa bacteria infecta cronicamente a mucosa gastroduodenal de uma grande parcela da populacao mundial. A infeccao por H. pylori esta associada ao desenvolvimento de diversas doencas gastroduodenais em humanos, entre elas a gastrite, a ulcera peptica (PUD) e seus subtipos, ulcera gastrica (GU) e duodenal (DU), e o adenocarcinoma gastrico. Embora a porcentagem de infectados seja alta, podendo chegar a 90% nos paises em desenvolvimento como o Brasil, somente uma pequena parcela dos individuos infectados desenvolve patologias graves. O desenvolvimento de doencas gastricas em individuos infectados por H. pylori parece ser o resultado da interacao entre caracteristicas do hospedeiro, influencias ambientais e fatores de virulencia produzidos pela bacteria. Muitos fatores de virulencia provaveis, que contribuem para a patogenese, tem sido identificados em H. pylori, dentre os quais temos os genes da Ilha de Patogenicidade cag (PAIcag), e genes da zona de plasticidade de H. pylori. Embora sabe-se que muitos dos fatores de virulencia descritos (cagA, cagE, vacA) estejam associados, universalmente, a um aumento no risco de desenvolvimento de quadros clinicos graves como ulcera peptica e câncer gastrico, nenhum deles pode ser ligado a uma doenca especifica causada pela infeccao persistente por H. pylori, e portanto ainda nao foi descrito um gene marcador universal para uma doenca resultante da infeccao por essa bacteria. Dados da literatura mostram uma associacao entre o gene cagT da PAIcag e o desenvolvimento de PUD. Um trabalho recente descreveu o locus dupA e sua associacao com o desenvolvimento de DU, e dupA foi sugerido como marcador universal para DU. Neste trabalho, investigou-se a presenca dos genes virB11 e cagT, localizados na PAIcag, e dos genes jhp917 e jhp918, integrantes do locus dupA encontrado zona de plasticidade de H.pylori, em isolados brasileiros dessa bacteria. Alem disso, investigou-se uma possivel associacao entre tais genes e algumas doencas decorrentes da infeccao por H. pylori, tais como a gastrite, PUD, GU, DU e a doenca do refluxo gastroesofagico (GERD), na tentativa de encontrar um gene marcador para alguma dessas doencas. Nossos resultados mostram que o gene cagT foi associado com PUD; o gene virB11 foi detectado em quase todas as amostras; o locus dupA nao foi associado a DU ou nenhuma outra doenca gastroduodenal. Dessa forma, nossos resultados sugerem que o gene cagT pode ser usado como marcador para o desenvolvimento de PUD no Estado de Sao Paulo, Brasil; o gene virB11 pode representar um gene de virulencia essencial para a patogenese da infeccao causada por H. pylori no desenvolvimento de gastrite, PUD e GERD; o locus dupA nao e um marcador universal para o desenvolvimento de DU Abstract

CagA

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Inter-kingdom signaling: chemical language between bacteria and host

Current Opinion in Microbiology (2009)

Alline R. Pacheco Vanessa Sperandio

Autoinducer

Chemical communication

Cell Signaling

10.1016/j.mib.2009.01.006

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Citations (181)

The Characterization of the Fucose Sensing Kinase (FUSK) and the Fucose Sensing Response Regulator (FUSR) and Their Role in Virulence Regulation in Enterohemorrhagic Escherichia Coli O157:H7

Alline R. Pacheco

Response regulator

Characterization

Source

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Enteric Pathogens Exploit the Microbiota-generated Nutritional Environment of the Gut

Microbiology Spectrum (2015)

Alline R. Pacheco Vanessa Sperandio

Host bacterial associations have a profound impact on health and disease. The human gastrointestinal (GI) tract is inhabited by trillions of commensal bacteria that aid in the digestion of food and vitamin production and play crucial roles in human physiology. Disruption of these relationships and the structure of the bacterial communities that inhabit the gut can contribute to dysbiosis, leading to disease. This fundamental relationship between the host and microbiota relies on chemical signaling and nutrient availability and exchange. GI pathogens compete with the endogenous microbiota for a colonization niche (1, 2). The ability to monitor nutrients and combine this information with the host physiological state is important for the pathogen to precisely program the expression of its virulence repertoire. A major nutrient source is carbon, and although the impact of carbon nutrition on the colonization of the gut by the microbiota has been extensively studied, the extent to which carbon sources affect the regulation of virulence factors by invading pathogens has not been fully defined. The GI pathogen enterohemorrhagic E. coli (EHEC) gages sugar sources as an important cue to regulate expression of its virulence genes. EHEC senses whether it is in a gluconeogenic versus a glycolytic environment, as well as fluctuations of fucose levels to fine tune regulation of its virulence repertoire.

Dysbiosis

Commensalism

Human pathogen

10.1128/microbiolspec.mbp-0001-2014

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Citations (47)