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  1. Article ; Online: Infant diarrheal disease in rhesus macaques impedes microbiome maturation and is linked to uncultured Campylobacter species.

    Rhoades, Nicholas S / Cinco, Isaac R / Hendrickson, Sara M / Prongay, Kamm / Haertel, Andrew J / Flores, Gilberto E / Slifka, Mark K / Messaoudi, Ilhem

    Communications biology

    2024  Volume 7, Issue 1, Page(s) 37

    Abstract: Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of ... ...

    Abstract Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans. Yet to be cultured Campylobacter spp. contribute to the total burden in diarrheal disease in children living in LMIC thus hampering interventions. We performed microbiome profiling and metagenomic genome assembly on samples collected from over 100 infant rhesus macaques longitudinally and during cases of clinical diarrhea within the first year of life. Acute diarrhea was associated with long-lasting taxonomic and functional shifts of the infant gut microbiome indicative of microbiome immaturity. We constructed 36 Campylobacter metagenomic assembled genomes (MAGs), many of which fell within 4 yet to be cultured species. Finally, we compared the uncultured Campylobacter MAGs assembled from infant macaques with publicly available human metagenomes to show that these uncultured species are also found in human fecal samples from LMIC. These data highlight the importance of unculturable Campylobacter spp. as an important target for reducing disease burden in LMIC children.
    MeSH term(s) Child ; Infant ; Animals ; Humans ; Macaca mulatta ; Campylobacter/genetics ; Microbiota ; Metagenome ; Diarrhea
    Language English
    Publishing date 2024-01-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05695-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Taxonomic and Functional Shifts in the Perinatal Gut Microbiome of Rhesus Macaques.

    Rhoades, Nicholas S / Cinco, Isaac R / Hendrickson, Sara M / Slifka, Mark K / Messaoudi, Ilhem

    Microbiology spectrum

    2022  Volume 10, Issue 4, Page(s) e0081422

    Abstract: Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal ... ...

    Abstract Pregnancy and the postpartum period result in some of the most dramatic metabolic, hormonal, and physiological changes that can be experienced by an otherwise healthy adult. The timing and magnitude of these changes is key for both maternal and fetal health. One of the factors believed to critically modulate these physiological changes is the maternal gut microbiome. However, the dynamic changes in this community during the perinatal period remain understudied. Clinical studies can be complicated by confounding variables like diet and other drivers of heterogeneity in the human microbiome. Therefore, in this study, we conducted a longitudinal analysis of the fecal microbiome obtained during the pregnancy and postpartum periods in 26 captive rhesus macaques using 16S rRNA gene amplicon sequencing and shotgun metagenomics. Shifts at both the taxonomic and functional potential level were detected when comparing pregnancy to postpartum samples. Taxonomically, Alloprevotella, Actinobacillus, and Anaerovibrio were enriched in the gut microbiome during pregnancy, while Treponema,
    MeSH term(s) Adult ; Animals ; Butyrates ; Feces ; Female ; Folic Acid ; Gastrointestinal Microbiome/physiology ; Humans ; Infant, Newborn ; Macaca mulatta/genetics ; Macaca mulatta/metabolism ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; Starch
    Chemical Substances Butyrates ; RNA, Ribosomal, 16S ; Starch (9005-25-8) ; Folic Acid (935E97BOY8)
    Language English
    Publishing date 2022-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.00814-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Active Circulation of Corynebacterium ulcerans among Nonhuman Primates.

    Thomas, Archana / Slifka, Ariel M / Hendrickson, Sara M / Amanna, Ian J / Slifka, Mark K

    Microbiology spectrum

    2022  Volume 10, Issue 4, Page(s) e0089422

    Abstract: Diphtheria is rare in the United States. and many industrialized nations due to development of an effective vaccine, coupled with high vaccination coverage. Although there is continued risk of importation and transmission of Corynebacterium diphtheriae, ... ...

    Abstract Diphtheria is rare in the United States. and many industrialized nations due to development of an effective vaccine, coupled with high vaccination coverage. Although there is continued risk of importation and transmission of Corynebacterium diphtheriae, C. ulcerans has now become the dominant source of diphtheria cases among several European countries. Bearing this in mind, a better understanding of C. ulcerans biology is clearly needed. Here, we identified active transmission of toxigenic C. ulcerans among indoor- and outdoor-housed rhesus macaques based on diphtheria toxin-specific serology assays as well as direct isolation of C. ulcerans from a recently infected animal. In addition to animal-to-animal transmission, we found serological evidence indicative of potential human transmission. Together, these results provide new details on natural Corynebacterium transmission among nonhuman primates and emphasizes the importance of maintaining high vaccination coverage to reduce the risk of potential zoonotic infection.
    MeSH term(s) Animals ; Corynebacterium ; Diphtheria ; Humans ; Macaca mulatta ; Retrospective Studies
    Language English
    Publishing date 2022-07-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.00894-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Campylobacter vaccination reduces diarrheal disease and infant growth stunting among rhesus macaques.

    Hendrickson, Sara M / Thomas, Archana / Raué, Hans-Peter / Prongay, Kamm / Haertel, Andrew J / Rhoades, Nicholas S / Slifka, Jacob F / Gao, Lina / Quintel, Benjamin K / Amanna, Ian J / Messaoudi, Ilhem / Slifka, Mark K

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 3806

    Abstract: Campylobacter-associated enteric disease is estimated to be responsible for more than 160 million cases of gastroenteritis each year and is linked to growth stunting of infants living under conditions of poor sanitation and hygiene. Here, we examine ... ...

    Abstract Campylobacter-associated enteric disease is estimated to be responsible for more than 160 million cases of gastroenteritis each year and is linked to growth stunting of infants living under conditions of poor sanitation and hygiene. Here, we examine naturally occurring Campylobacter-associated diarrhea among rhesus macaques as a model to determine if vaccination could reduce severe diarrheal disease and infant growth stunting. Compared to unvaccinated controls, there are no Campylobacter diarrhea-associated deaths observed among vaccinated infant macaques and all-cause diarrhea-associated infant mortality is decreased by 76% (P = 0.03). By 9 months of age, there is a 1.3 cm increase in dorsal length that equaled a significant 1.28 LAZ (Length-for-Age Z score) improvement in linear growth among vaccinated infants compared to their unvaccinated counterparts (P = 0.001). In this work, we show that Campylobacter vaccination not only reduces diarrheal disease but also potentially serves as an effective intervention that improves infant growth trajectories.
    MeSH term(s) Animals ; Campylobacter ; Macaca mulatta ; Diarrhea/prevention & control ; Growth Disorders/prevention & control ; Campylobacter Infections/prevention & control
    Language English
    Publishing date 2023-06-26
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-39433-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Longitudinal Profiling of the Macaque Vaginal Microbiome Reveals Similarities to Diverse Human Vaginal Communities.

    Rhoades, Nicholas S / Hendrickson, Sara M / Gerken, Danielle R / Martinez, Kassandra / Slayden, Ov D / Slifka, Mark K / Messaoudi, Ilhem

    mSystems

    2021  Volume 6, Issue 2

    Abstract: The vaginal microbiota plays an important role in women's reproductive and urogenital health. It is now well accepted that a "healthy" vaginal microbiome is dominated ... ...

    Abstract The vaginal microbiota plays an important role in women's reproductive and urogenital health. It is now well accepted that a "healthy" vaginal microbiome is dominated by
    Language English
    Publishing date 2021-04-27
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5077
    ISSN 2379-5077
    DOI 10.1128/mSystems.01322-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen.

    Rhoades, Nicholas S / Hendrickson, Sara M / Prongay, Kamm / Haertel, Andrew / Gill, Leanne / Edwards, Robert A / Garzel, Laura / Slifka, Mark K / Messaoudi, Ilhem

    Mucosal immunology

    2021  Volume 14, Issue 5, Page(s) 1113–1126

    Abstract: Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally ... ...

    Abstract Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea. We show that growth faltering in the presence or absence of active diarrhea is associated with a heightened systemic and mucosal pro-inflammatory state centered in the colon. Moreover, polyclonal stimulation of colonic lamina propria leukocytes resulted in a dampened cytokine response, indicative of immune exhaustion. We also detected a functional and taxonomic shift in the luminal microbiome across multiple gut sites including the migration of Streptococcus and Prevotella species between the small and large intestine, suggesting a decompartmentalization of gut microbial communities. Our studies provide valuable insight into the outcomes of diarrheal diseases and growth faltering not attainable in humans and lays the groundwork to test interventions in a controlled and reproducible setting.
    MeSH term(s) Animals ; Biodiversity ; Biomarkers ; Biopsy ; Chronic Disease ; Diarrhea/complications ; Diarrhea/etiology ; Diarrhea/metabolism ; Diarrhea/pathology ; Disease Models, Animal ; Disease Susceptibility ; Dysbiosis/complications ; Dysbiosis/immunology ; Gastrointestinal Microbiome/immunology ; Growth Disorders/etiology ; Growth Disorders/metabolism ; Immunity, Mucosal/genetics ; Immunohistochemistry ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Lymphocyte Count ; Macaca mulatta ; Metagenome ; Metagenomics/methods ; Transcriptome
    Chemical Substances Biomarkers
    Language English
    Publishing date 2021-06-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2411370-0
    ISSN 1935-3456 ; 1933-0219
    ISSN (online) 1935-3456
    ISSN 1933-0219
    DOI 10.1038/s41385-021-00418-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Reduced infant rhesus macaque growth rates due to environmental enteric dysfunction and association with histopathology in the large intestine.

    Hendrickson, Sara M / Thomas, Archana / Prongay, Kamm / Haertel, Andrew J / Garzel, Laura M / Gill, Leanne / Barr, Tasha / Rhoades, Nicholas S / Reader, Rachel / Galan, Mark / Carroll, Julie M / Roberts, Charles T / Gao, Lina / Amanna, Ian J / Messaoudi, Ilhem / Slifka, Mark K

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 234

    Abstract: Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized ... ...

    Abstract Environmental enteric dysfunction is associated with malnutrition as well as infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, and inflammation in the small intestine. Here, we characterized environmental enteric dysfunction among infant rhesus macaques that are naturally exposed to enteric pathogens commonly linked to human growth stunting. Remarkably, despite villous atrophy and histological abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan levels were correlated with increased histopathology in the large intestine. This work provides insight into the mechanisms underlying this disease and indicates that the large intestine may be an important target for therapeutic intervention.
    MeSH term(s) Animals ; Duodenum/pathology ; Female ; Gastrointestinal Tract ; Gene Expression ; Growth Disorders/pathology ; Humans ; Ileum/pathology ; Inflammation ; Intestinal Diseases ; Intestinal Mucosa ; Intestine, Large/pathology ; Intestine, Small/pathology ; Jejunum/pathology ; Macaca mulatta/growth & development ; Male ; Malnutrition
    Language English
    Publishing date 2022-01-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-021-27925-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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