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  1. Artikel ; Online: Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.

    Sheikh, Irshad Ali / Bianchi-Smak, Jared / Laubitz, Daniel / Schiro, Gabriele / Midura-Kiela, Monica T / Besselsen, David G / Vedantam, Gayatri / Jarmakiewicz, Sara / Filip, Rafał / Ghishan, Fayez K / Gao, Nan / Kiela, Pawel R

    Gut microbes

    2024  Band 16, Heft 1, Seite(n) 2333483

    Abstract: Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in ... ...

    Abstract Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of
    Mesh-Begriff(e) Humans ; Mice ; Animals ; Crohn Disease/microbiology ; Clostridioides difficile ; Gastrointestinal Microbiome ; Colitis ; Microbiota ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology
    Sprache Englisch
    Erscheinungsdatum 2024-03-27
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2575755-6
    ISSN 1949-0984 ; 1949-0984
    ISSN (online) 1949-0984
    ISSN 1949-0984
    DOI 10.1080/19490976.2024.2333483
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Decreased NHE3 expression in colon cancer is associated with DNA damage, increased inflammation and tumor growth.

    Laubitz, Daniel / Gurney, Michael A / Midura-Kiela, Monica / Clutter, Christy / Besselsen, David G / Chen, Hao / Ghishan, Fayez K / Kiela, Pawel R

    Scientific reports

    2022  Band 12, Heft 1, Seite(n) 14725

    Abstract: Dysregulation of intra- and extracellular pH in cancer contributes to extracellular matrix remodeling, favors cell migration, proliferation, and metastasis. Although the primary attention has been focused on the role of the ubiquitous ... ...

    Abstract Dysregulation of intra- and extracellular pH in cancer contributes to extracellular matrix remodeling, favors cell migration, proliferation, and metastasis. Although the primary attention has been focused on the role of the ubiquitous Na
    Mesh-Begriff(e) Animals ; Colonic Neoplasms/genetics ; Colonic Neoplasms/pathology ; DNA Damage ; Inflammation/genetics ; Mice ; Protein Isoforms/metabolism ; Sodium-Hydrogen Exchanger 3/genetics ; Sodium-Hydrogen Exchangers/genetics ; Sodium-Hydrogen Exchangers/metabolism
    Chemische Substanzen Protein Isoforms ; Slc9a3 protein, mouse ; Sodium-Hydrogen Exchanger 3 ; Sodium-Hydrogen Exchangers
    Sprache Englisch
    Erscheinungsdatum 2022-08-30
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-022-19091-x
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel: Intestinal Regulatory T Cells.

    Figliuolo da Paz, Vanessa R / Jamwal, Deepa R / Kiela, Pawel R

    Advances in experimental medicine and biology

    2021  Band 1278, Seite(n) 141–190

    Abstract: Mucosal surfaces are distinctive sites exposed to environmental, dietary, and microbial antigens. Particularly in the gut, the host continuously actively adapts via complex interactions between the microbiota and dietary compounds and immune and other ... ...

    Abstract Mucosal surfaces are distinctive sites exposed to environmental, dietary, and microbial antigens. Particularly in the gut, the host continuously actively adapts via complex interactions between the microbiota and dietary compounds and immune and other tissue cells. Regulatory T cells (Tregs) are critical for tuning the intestinal immune response to self- and non-self-antigens in the intestine. Its importance in intestinal homeostasis is illustrated by the onset of overt inflammation caused by deficiency in Treg generation, function, or stability in the gut. A substantial imbalance in Tregs has been observed in intestinal tissue during pathogenic conditions, when a tightly regulated and equilibrated system becomes dysregulated and leads to unimpeded and chronic immune responses. In this chapter, we compile and critically discuss the current knowledge on the key factors that promote Treg-mediated tolerance in the gut, such as those involved in intestinal Treg differentiation, specificity and suppressive function, and their immunophenotype during health and disease. We also discuss the current state of knowledge on Treg dysregulation in human intestine during pathological states such as inflammatory bowel disease (IBD), necrotizing enterocolitis (NEC), graft-versus-host disease (GVHD), and colorectal cancer (CRC), and how that knowledge is guiding development of Treg-targeted therapies to treat or prevent intestinal disorders.
    Mesh-Begriff(e) Colitis ; Humans ; Immune Tolerance ; Infant, Newborn ; Inflammation ; Inflammatory Bowel Diseases ; Intestinal Mucosa ; T-Lymphocytes, Regulatory
    Sprache Englisch
    Erscheinungsdatum 2021-01-30
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-981-15-6407-9_9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel: Dynamics of Gut Microbiota Recovery after Antibiotic Exposure in Young and Old Mice (A Pilot Study).

    Laubitz, Daniel / Typpo, Katri / Midura-Kiela, Monica / Brown, Clairessa / Barberán, Albert / Ghishan, Fayez K / Kiela, Pawel R

    Microorganisms

    2021  Band 9, Heft 3

    Abstract: Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older ... ...

    Abstract Antibiotics have improved survival from previously deadly infectious diseases. Antibiotics alter the microbial composition of the gut microbiota, and these changes are associated with diminished innate immunity and decline in cognitive function in older adults. The composition of the human microbiota changes with age over the human lifespan. In this pilot study, we sought to identify if age is associated with differential recovery of the microbiota after antibiotic exposure. Using 16S rRNA gene sequencing, we compared recovery of the gut microbiota after the 10-day broad-spectrum antibiotic treatment in wild-type C57BL/six young and older mice. Immediately after antibiotic cessation, as expected, the number of ASVs, representing taxonomic richness, in both young and older mice significantly declined from the baseline. Mice were followed up to 6 months after cessation of the single 10-day antibiotic regimen. The Bray-Curtis index recovered within 20 days after antibiotic cessation in young mice, whereas in older mice the microbiota did not fully recover during the 6-months of follow-up.
    Sprache Englisch
    Erscheinungsdatum 2021-03-20
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9030647
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Vitamins and Minerals in Inflammatory Bowel Disease.

    Ghishan, Fayez K / Kiela, Pawel R

    Gastroenterology clinics of North America

    2017  Band 46, Heft 4, Seite(n) 797–808

    Abstract: Indiscriminate use of multivitamin/mineral supplements in the general population may be misguided, but patients with chronic Inflammatory Bowel Diseases (IBD) should be monitored and compensated for nutritional deficiencies. Mechanistic links between ... ...

    Abstract Indiscriminate use of multivitamin/mineral supplements in the general population may be misguided, but patients with chronic Inflammatory Bowel Diseases (IBD) should be monitored and compensated for nutritional deficiencies. Mechanistic links between vitamin/mineral deficiencies and IBD pathology has been found for some micronutrients and normalizing their levels is clinically beneficial. Others, like vitamin A, although instinctively desirable, produced disappointing results. Restoring normal levels of the selected micronutrients requires elevated doses to compensate for defects in absorptive or signaling mechanisms. This article describes some aspects of vitamin and mineral deficiencies in IBD, and summarizes pros and cons of supplementation.
    Mesh-Begriff(e) Anemia, Iron-Deficiency/complications ; Animals ; Avitaminosis/complications ; Avitaminosis/drug therapy ; Biotin/therapeutic use ; Calcium/therapeutic use ; Cholecalciferol/therapeutic use ; Dietary Supplements ; Folic Acid/therapeutic use ; Humans ; Inflammatory Bowel Diseases/complications ; Inflammatory Bowel Diseases/drug therapy ; Iron/therapeutic use ; Thiamine/therapeutic use ; Vitamin A/therapeutic use ; Vitamin B 12/therapeutic use ; Vitamin B 6/therapeutic use ; Vitamin K/therapeutic use ; Vitamins/therapeutic use ; Zinc/deficiency ; Zinc/therapeutic use
    Chemische Substanzen Vitamins ; Vitamin A (11103-57-4) ; Vitamin K (12001-79-5) ; Cholecalciferol (1C6V77QF41) ; Biotin (6SO6U10H04) ; Vitamin B 6 (8059-24-3) ; Folic Acid (935E97BOY8) ; Iron (E1UOL152H7) ; Zinc (J41CSQ7QDS) ; Vitamin B 12 (P6YC3EG204) ; Calcium (SY7Q814VUP) ; Thiamine (X66NSO3N35)
    Sprache Englisch
    Erscheinungsdatum 2017-10-03
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Review
    ZDB-ID 92114-2
    ISSN 1558-1942 ; 0889-8553
    ISSN (online) 1558-1942
    ISSN 0889-8553
    DOI 10.1016/j.gtc.2017.08.011
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Interactions between arsenic exposure, high-fat diet and NRF2 shape the complex responses in the murine gut microbiome and hepatic metabolism.

    Schiro, Gabriele / Liu, Pengfei / Dodson, Matthew / Zhang, Donna D / Ghishan, Fayez K / Barberán, Albert / Kiela, Pawel R

    Frontiers in microbiomes

    2022  Band 1

    Abstract: Inorganic arsenic (iAs) exposure has been associated to various detrimental effects such as development of metabolic syndrome and type 2 diabetes via oxidative stress and induced prolonged activation of the NRF2 transcription factor. Such effects can be ... ...

    Abstract Inorganic arsenic (iAs) exposure has been associated to various detrimental effects such as development of metabolic syndrome and type 2 diabetes via oxidative stress and induced prolonged activation of the NRF2 transcription factor. Such effects can be aggravated by poor dietary habits. The role of gut microbiota in promoting metabolic changes in response to arsenic has yet to be precisely defined. To address the complexity of the interactions between diet,
    Sprache Englisch
    Erscheinungsdatum 2022-11-23
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article
    ISSN 2813-4338
    ISSN (online) 2813-4338
    DOI 10.3389/frmbi.2022.1041188
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Emerging Roles of Disabled Homolog 2 (DAB2) in Immune Regulation.

    Figliuolo da Paz, Vanessa / Ghishan, Fayez K / Kiela, Pawel R

    Frontiers in immunology

    2020  Band 11, Seite(n) 580302

    Abstract: Disabled-2 (DAB2) is a clathrin and cargo binding endocytic adaptor protein recognized for its multifaceted roles in signaling pathways involved in cellular differentiation, proliferation, migration, tumor suppression, and other fundamental homeostatic ... ...

    Abstract Disabled-2 (DAB2) is a clathrin and cargo binding endocytic adaptor protein recognized for its multifaceted roles in signaling pathways involved in cellular differentiation, proliferation, migration, tumor suppression, and other fundamental homeostatic cellular mechanisms. The requirement for DAB2 in the canonical TGFβ signaling in fibroblasts suggested that a similar mechanism may exist in immune cells and that DAB2 may contribute to immunological tolerance and suppression of inflammatory responses. In this review, we synthesize the current state of knowledge on the roles of DAB2 in the cells of the innate and adaptive immune system, with particular focus on antigen presenting cells (APCs; macrophages and dendritic cells) and regulatory T cells (Tregs). The emerging role of DAB2 in the immune system is that of an immunoregulatory molecule with significant roles in Treg-mediated immunosuppression, and suppression of TLR signaling in APC. DAB2 itself is downregulated by inflammatory stimuli, an event that likely contributes to the immunogenic function of APC. However, contrary findings have been described in neuroinflammatory disorders, thus suggesting a highly context-specific roles for DAB2 in immune cell regulation. There is need for better understanding of DAB2 regulation and its roles in different immune cells, their specialized sub-populations, and their responses under specific inflammatory conditions.
    Mesh-Begriff(e) Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Antigen Presentation ; Apoptosis Regulatory Proteins/genetics ; Apoptosis Regulatory Proteins/metabolism ; Dendritic Cells/immunology ; Humans ; Inflammation/immunology ; Lymphocytes/immunology ; Signal Transduction ; T-Lymphocytes, Regulatory/immunology ; Transforming Growth Factor beta/metabolism
    Chemische Substanzen Adaptor Proteins, Signal Transducing ; Apoptosis Regulatory Proteins ; DAB2 protein, human ; Transforming Growth Factor beta
    Sprache Englisch
    Erscheinungsdatum 2020-10-15
    Erscheinungsland Switzerland
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.580302
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: SLC9 Gene Family: Function, Expression, and Regulation.

    Xu, Hua / Ghishan, Fayez K / Kiela, Pawel R

    Comprehensive Physiology

    2018  Band 8, Heft 2, Seite(n) 555–583

    Abstract: The Slc9 family of ... ...

    Abstract The Slc9 family of Na
    Mesh-Begriff(e) Animals ; Digestive System/metabolism ; Gastrointestinal Diseases/genetics ; Gastrointestinal Diseases/metabolism ; Gene Expression Regulation/physiology ; Humans ; Intestinal Absorption/genetics ; Intestinal Absorption/physiology ; Salivary Glands/physiology ; Sodium-Hydrogen Exchangers/genetics ; Sodium-Hydrogen Exchangers/physiology
    Chemische Substanzen Sodium-Hydrogen Exchangers
    Sprache Englisch
    Erscheinungsdatum 2018-03-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 2040-4603
    ISSN (online) 2040-4603
    DOI 10.1002/cphy.c170027
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Physiology of Intestinal Absorption and Secretion.

    Kiela, Pawel R / Ghishan, Fayez K

    Best practice & research. Clinical gastroenterology

    2016  Band 30, Heft 2, Seite(n) 145–159

    Abstract: Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are ... ...

    Abstract Virtually all nutrients from the diet are absorbed into blood across the highly polarized epithelial cell layer forming the small and large intestinal mucosa. Anatomical, histological, and functional specializations along the gastrointestinal tract are responsible for the effective and regulated nutrient transport via both passive and active mechanisms. In this chapter, we summarize the current state of knowledge regarding the mechanism of intestinal absorption of key nutrients such as sodium, anions (chloride, sulfate, oxalate), carbohydrates, amino acids and peptides, lipids, lipid- and water-soluble vitamins, as well as the major minerals and micronutrients. This outline, including the molecular identity, specificity, and coordinated activities of key transport proteins and genes involved, serves as the background for the following chapters focused on the pathophysiology of acquired and congenital intestinal malabsorption, as well as clinical tools to test and treat malabsorptive symptoms.
    Mesh-Begriff(e) Humans ; Intestinal Absorption/physiology ; Intestinal Mucosa/physiology ; Intestinal Secretions/physiology
    Sprache Englisch
    Erscheinungsdatum 2016-04
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Review
    ZDB-ID 2048181-0
    ISSN 1532-1916 ; 1521-6918
    ISSN (online) 1532-1916
    ISSN 1521-6918
    DOI 10.1016/j.bpg.2016.02.007
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel: Interactive Effect of Combined Intermittent and Sustained Hypoxia and High-Fat Diet on the Colonic Mucosal Microbiome and Host Gene Expression in Mice.

    Mashaqi, Saif / Laubitz, Daniel / Morales, Efreim Joseph D / De Armond, Richard / Alameddin, Hanan / Ghishan, Fayez K / Kiela, Pawel R / Parthasarathy, Sairam

    Nature and science of sleep

    2022  Band 14, Seite(n) 1623–1639

    Abstract: Purpose: Gut dysbiosis can cause cardiometabolic disease. Gut dysbiosis can be independently caused by high-fat diet (HFD) and intermittent hypoxia (IH; characterizing obstructive sleep apnea), but the interactive effect of combined intermittent and ... ...

    Abstract Purpose: Gut dysbiosis can cause cardiometabolic disease. Gut dysbiosis can be independently caused by high-fat diet (HFD) and intermittent hypoxia (IH; characterizing obstructive sleep apnea), but the interactive effect of combined intermittent and sustained hypoxia (IH+SH) (characterizing obesity hypoventilation syndrome) and HFD on gut dysbiosis is unclear. We aimed to investigate the interactive effect of a combination of IH and SH and HFD on proximal colonic microbiota and colonic gene expression pattern.
    Methods: Male mice (n=16) were randomly received four different combinations of diet (normal versus HFD) and oxygen conditions (normoxia versus IH+SH) for 4 weeks. Bacterial DNA and mucosal epithelial cell RNA from proximal colon were collected for analysis of adherent microbiome and host's gene expression analysis.
    Results: HFD during IH+SH (22.6 ± 5.73; SD) led to greater Firmicutes: Bacteroidetes ratio than HFD during normoxia (5.89 ± 1.19; p=0.029). HFD significantly decreased microbial diversity as compared to normal diet, but the addition of IH+SH to HFD mildly reversed such effects. When compared to HFD during normoxia, HFD with combination of IH+SH resulted in changes to host mucosal gene expression for apical junctional complexes and adhesion molecules. Specifically, when compared to HFD during normoxia, HFD during IH+SH led to upregulation of Claudin 2 and Syk (tight junction dysfunction and increased mucosal permeability), while the barrier promoting claudin 4 was downregulated.
    Conclusion: HFD during combined IH and SH causes greater gut dysbiosis and potentially adverse changes in colonic epithelial transcriptome than HFD during normoxia. The latter changes are suggestive of impaired gut barrier function.
    Sprache Englisch
    Erscheinungsdatum 2022-09-09
    Erscheinungsland New Zealand
    Dokumenttyp Journal Article
    ZDB-ID 2587468-8
    ISSN 1179-1608
    ISSN 1179-1608
    DOI 10.2147/NSS.S370957
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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