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Article ; Online: The gut microbiome.

Kuziel, Gavin A / Rakoff-Nahoum, Seth

2022 Volume 32, Issue 6, Page(s) R257–R264

Abstract: All animals, from cnidarians to humans, are colonized with microbes, and the greatest diversity and magnitude of these host-associated microorganisms resides within the intestine. Referred to as the gut microbiome, membership can be as simple as one ... ...

Abstract	All animals, from cnidarians to humans, are colonized with microbes, and the greatest diversity and magnitude of these host-associated microorganisms resides within the intestine. Referred to as the gut microbiome, membership can be as simple as one species of bacteria or can be composed of hundreds to thousands of different microbes across the domains of life. The relationship between the gut microbiome and host span from beneficial to detrimental; interactions may be context-dependent and occur across host physiology and organ systems. In this Primer, we focus on the mammalian host to discuss basic mechanisms by which the gut microbiome impacts the host and review mechanisms by which hosts and the environment shape the microbiome. We end by highlighting key concepts and discussing future directions for the field that will be critical for generating the next generation of knowledge of the gut microbiome.
MeSH term(s)	Animals ; Bacteria ; Gastrointestinal Microbiome/physiology ; Mammals ; Microbiota
Language	English
Publishing date	2022-03-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2022.02.023
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Article ; Online: Another Reason to Thank Mom: Gestational Effects of Microbiota Metabolites.

Rakoff-Nahoum, Seth

Cell host & microbe

2016 Volume 19, Issue 4, Page(s) 425–427

Abstract: Microbial colonization after birth profoundly affects development of the host. In a recent paper, Gomez de Agüero et al. (2016) reveal a new aspect of ontogeny influenced by the microbiota: the impact of gestational gut bacterial metabolites on early ... ...

Abstract	Microbial colonization after birth profoundly affects development of the host. In a recent paper, Gomez de Agüero et al. (2016) reveal a new aspect of ontogeny influenced by the microbiota: the impact of gestational gut bacterial metabolites on early immune maturation of the neonatal intestine.
MeSH term(s)	Animals ; Female ; Gastrointestinal Microbiome/immunology ; Immune System/growth & development ; Immune System/microbiology ; Immunity, Innate/immunology ; Immunity, Maternally-Acquired/immunology ; Intestines/immunology ; Pregnancy
Language	English
Publishing date	2016-04-12
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2278004-X
ISSN	1934-6069 ; 1931-3128
ISSN (online)	1934-6069
ISSN	1931-3128
DOI	10.1016/j.chom.2016.03.012
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Article ; Online: Ecological rules for the assembly of microbiome communities.

Coyte, Katharine Z / Rao, Chitong / Rakoff-Nahoum, Seth / Foster, Kevin R

PLoS biology

2021 Volume 19, Issue 2, Page(s) e3001116

Abstract: Humans and many other hosts establish a diverse community of beneficial microbes anew each generation. The order and identity of incoming symbionts is critical for health, but what determines the success of the assembly process remains poorly understood. ...

Abstract	Humans and many other hosts establish a diverse community of beneficial microbes anew each generation. The order and identity of incoming symbionts is critical for health, but what determines the success of the assembly process remains poorly understood. Here we develop ecological theory to identify factors important for microbial community assembly. Our method maps out all feasible pathways for the assembly of a given microbiome-with analogies to the mutational maps underlying fitness landscapes in evolutionary biology. Building these "assembly maps" reveals a tradeoff at the heart of the assembly process. Ecological dependencies between members of the microbiota make assembly predictable-and can provide metabolic benefits to the host-but these dependencies may also create barriers to assembly. This effect occurs because interdependent species can fail to establish when each relies on the other to colonize first. We support our predictions with published data from the assembly of the preterm infant microbiota, where we find that ecological dependence is associated with a predictable order of arrival. Our models also suggest that hosts can overcome barriers to assembly via mechanisms that either promote the uptake of multiple symbiont species in one step or feed early colonizers. This predicted importance of host feeding is supported by published data on the impacts of breast milk in the assembly of the human microbiome. We conclude that both microbe to microbe and host to microbe interactions are important for the trajectory of microbiome assembly.
MeSH term(s)	Humans ; Infant, Newborn ; Infant, Premature ; Microbiota ; Milk, Human/microbiology ; Models, Theoretical ; Symbiosis
Language	English
Publishing date	2021-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3001116
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Article: Stress Ulcer Prophylaxis Versus Placebo-A Blinded Pilot Randomized Controlled Trial to Evaluate the Safety of Two Strategies in Critically Ill Infants With Congenital Heart Disease.

Mills, Kimberly I / Albert, Ben D / Bechard, Lori J / Chu, Stephen / Duggan, Christopher P / Kaza, Aditya / Rakoff-Nahoum, Seth / Sleeper, Lynn A / Newburger, Jane W / Priebe, Gregory P / Mehta, Nilesh M

Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

2024 Volume 25, Issue 2, Page(s) 118–127

Abstract: Objectives: The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial ...

Abstract	Objectives: The routine use of stress ulcer prophylaxis (SUP) in infants with congenital heart disease (CHD) in the cardiac ICU (CICU) is controversial. We aimed to conduct a pilot study to explore the feasibility of performing a subsequent larger trial to assess the safety and efficacy of withholding SUP in this population (NCT03667703). Design, setting, patients: Single-center, prospective, double-blinded, parallel group (SUP vs. placebo), pilot randomized controlled pilot trial (RCT) in infants with CHD admitted to the CICU and anticipated to require respiratory support for greater than 24 hours. Interventions: Patients were randomized 1:1 (stratified by age and admission type) to receive a histamine-2 receptor antagonist or placebo until respiratory support was discontinued, up to 14 days, or transfer from the CICU, if earlier. Measurements and main results: Feasibility was defined a priori by thresholds of screening rate, consent rate, timely drug allocation, and protocol adherence. The safety outcome was the rate of clinically significant upper gastrointestinal (UGI) bleeding. We screened 1,426 patients from February 2019 to March 2022; of 132 eligible patients, we gained informed consent in 70 (53%). Two patients did not require CICU admission after obtaining consent, and the remaining 68 patients were randomized to SUP (n = 34) or placebo (n = 34). Ten patients were withdrawn early, because of a change in eligibility (n = 3) or open-label SUP use (n = 7, 10%). Study procedures were completed in 58 patients (89% protocol adherence). All feasibility criteria were met. There were no clinically significant episodes of UGI bleeding during the pilot RCT. The percentage of patients with other nonserious adverse events did not differ between groups. Conclusions: Withholding of SUP in infants with CHD admitted to the CICU was feasible. A larger multicenter RCT designed to confirm the safety of this intervention and its impact on incidence of UGI bleeding, gastrointestinal microbiome, and other clinical outcomes is warranted.
MeSH term(s)	Humans ; Critical Illness/therapy ; Gastrointestinal Hemorrhage/prevention & control ; Heart Defects, Congenital/complications ; Peptic Ulcer/prevention & control ; Pilot Projects ; Treatment Outcome ; Ulcer/complications ; Infant
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2052349-X
ISSN	1947-3893 ; 1529-7535
ISSN (online)	1947-3893
ISSN	1529-7535
DOI	10.1097/PCC.0000000000003384
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Zs.A 5600: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Understanding Competition and Cooperation within the Mammalian Gut Microbiome.

Coyte, Katharine Z / Rakoff-Nahoum, Seth

Current biology : CB

2019 Volume 29, Issue 11, Page(s) R538–R544

Abstract: The mammalian gut harbors a vast community of microorganisms - termed the microbiota - whose composition and dynamics are considered to be critical drivers of host health. These factors depend, in part, upon the manner in which microbes interact with one ...

Abstract	The mammalian gut harbors a vast community of microorganisms - termed the microbiota - whose composition and dynamics are considered to be critical drivers of host health. These factors depend, in part, upon the manner in which microbes interact with one another. Microbes are known to engage in a myriad of different ways, ranging from unprovoked aggression to actively feeding each other. However, the relative extent to which these different interactions occur between microbes within the gut is unclear. In this minireview we assess our current knowledge of microbe-microbe interactions within the mammalian gut microbiota, and the array of methods used to uncover them. In particular, we highlight the discrepancies between different methodologies: some studies have revealed rich networks of cross-feeding interactions between microbes, whereas others suggest that microbes are more typically locked in conflict and actively cooperate only rarely. We argue that to reconcile these contradictions we must recognize that interactions between members of the microbiota can vary across condition, space, and time - and that only through embracing this dynamism will we be able to comprehensively understand the ecology of our gut communities.
MeSH term(s)	Animals ; Gastrointestinal Microbiome ; Mammals/microbiology ; Microbial Interactions
Language	English
Publishing date	2019-07-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2019.04.017
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Article: Enteric glia regulate Paneth cell secretion and intestinal microbial ecology.

Prochera, Aleksandra / Muppirala, Anoohya N / Kuziel, Gavin A / Soualhi, Salima / Shepherd, Amy / Sun, Liang / Issac, Biju / Rosenberg, Harry J / Karim, Farah / Perez, Kristina / Smith, Kyle H / Archibald, Tonora H / Rakoff-Nahoum, Seth / Hagen, Susan J / Rao, Meenakshi

bioRxiv : the preprint server for biology

2024

Abstract: Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier ... ...

Abstract	Glial cells of the enteric nervous system (ENS) interact closely with the intestinal epithelium and secrete signals that influence epithelial cell proliferation and barrier formation
Language	English
Publishing date	2024-04-19
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.04.15.589545
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Article ; Online: Bacterial amylases enable glycogen degradation by the vaginal microbiome.

Jenkins, Dominick J / Woolston, Benjamin M / Hood-Pishchany, M Indriati / Pelayo, Paula / Konopaski, Alyssa N / Quinn Peters, M / France, Michael T / Ravel, Jacques / Mitchell, Caroline M / Rakoff-Nahoum, Seth / Whidbey, Christopher / Balskus, Emily P

Nature microbiology

2023 Volume 8, Issue 9, Page(s) 1641–1652

Abstract: The human vaginal microbiota is frequently dominated by lactobacilli and transition to a more diverse community of anaerobic microbes is associated with health risks. Glycogen released by lysed epithelial cells is believed to be an important nutrient ... ...

Abstract	The human vaginal microbiota is frequently dominated by lactobacilli and transition to a more diverse community of anaerobic microbes is associated with health risks. Glycogen released by lysed epithelial cells is believed to be an important nutrient source in the vagina. However, the mechanism by which vaginal bacteria metabolize glycogen is unclear, with evidence implicating both bacterial and human enzymes. Here we biochemically characterize six glycogen-degrading enzymes (GDEs), all of which are pullanases (PulA homologues), from vaginal bacteria that support the growth of amylase-deficient Lactobacillus crispatus on glycogen. We reveal variations in their pH tolerance, substrate preferences, breakdown products and susceptibility to inhibition. Analysis of vaginal microbiome datasets shows that these enzymes are expressed in all community state types. Finally, we confirm the presence and activity of bacterial and human GDEs in cervicovaginal fluid. This work establishes that bacterial GDEs can participate in the breakdown of glycogen, providing insight into metabolism that may shape the vaginal microbiota.
MeSH term(s)	Female ; Humans ; Amylases ; Vagina/microbiology ; Bacteria/genetics ; Bacteria/metabolism ; Microbiota/physiology ; Glycogen/metabolism
Chemical Substances	Amylases (EC 3.2.1.-) ; Glycogen (9005-79-2)
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2058-5276
ISSN (online)	2058-5276
DOI	10.1038/s41564-023-01447-2
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Article ; Online: Distribution and storage of inflammatory memory in barrier tissues.

Ordovas-Montanes, Jose / Beyaz, Semir / Rakoff-Nahoum, Seth / Shalek, Alex K

Nature reviews. Immunology

2020 Volume 20, Issue 5, Page(s) 308–320

Abstract: Memories of previous immune events enable barrier tissues to rapidly recall distinct environmental exposures. To effectively inform future responses, these past experiences can be stored in cell types that are long-term residents or essential ... ...

Abstract	Memories of previous immune events enable barrier tissues to rapidly recall distinct environmental exposures. To effectively inform future responses, these past experiences can be stored in cell types that are long-term residents or essential constituents of tissues. There is an emerging understanding that, in addition to antigen-specific immune cells, diverse haematopoietic, stromal, parenchymal and neuronal cell types can store inflammatory memory. Here, we explore the impact of previous immune activity on various cell lineages with the goal of presenting a unified view of inflammatory memory to environmental exposures (such as allergens, antigens, noxious agents and microorganisms) at barrier tissues. We propose that inflammatory memory is distributed across diverse cell types and stored through shifts in cell states, and we provide a framework to guide future experiments. This distribution and storage may promote adaptation or maladaptation in homeostatic, maintenance and disease settings - especially if the distribution of memory favours cellular cooperation during storage or recall.
MeSH term(s)	Adaptive Immunity ; B-Lymphocytes/immunology ; Cell Lineage ; Dendritic Cells/immunology ; Epithelial Cells/immunology ; Epithelium/immunology ; Humans ; Immunity, Innate ; Immunologic Memory/immunology ; Inflammation/immunology ; Macrophages/immunology ; Neurons/immunology ; Plasma Cells/immunology ; Stromal Cells/immunology ; T-Lymphocytes/immunology
Language	English
Publishing date	2020-02-03
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/s41577-019-0263-z
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Zs.A 5565: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Multi-kingdom ecological drivers of microbiota assembly in preterm infants.

Rao, Chitong / Coyte, Katharine Z / Bainter, Wayne / Geha, Raif S / Martin, Camilia R / Rakoff-Nahoum, Seth

Nature

2021 Volume 591, Issue 7851, Page(s) 633–638

Abstract: The gut microbiota of preterm infants develops ... ...

Abstract	The gut microbiota of preterm infants develops predictably
MeSH term(s)	Bacterial Load ; Biodiversity ; Diet ; Female ; Gastrointestinal Microbiome ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Male ; Microbial Interactions ; Reproducibility of Results
Language	English
Publishing date	2021-02-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-03241-8
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Article ; Online: Ecological rules for the assembly of microbiome communities.

Katharine Z Coyte / Chitong Rao / Seth Rakoff-Nahoum / Kevin R Foster

PLoS Biology, Vol 19, Iss 2, p e

2021 Volume 3001116

Abstract	Humans and many other hosts establish a diverse community of beneficial microbes anew each generation. The order and identity of incoming symbionts is critical for health, but what determines the success of the assembly process remains poorly understood. Here we develop ecological theory to identify factors important for microbial community assembly. Our method maps out all feasible pathways for the assembly of a given microbiome-with analogies to the mutational maps underlying fitness landscapes in evolutionary biology. Building these "assembly maps" reveals a tradeoff at the heart of the assembly process. Ecological dependencies between members of the microbiota make assembly predictable-and can provide metabolic benefits to the host-but these dependencies may also create barriers to assembly. This effect occurs because interdependent species can fail to establish when each relies on the other to colonize first. We support our predictions with published data from the assembly of the preterm infant microbiota, where we find that ecological dependence is associated with a predictable order of arrival. Our models also suggest that hosts can overcome barriers to assembly via mechanisms that either promote the uptake of multiple symbiont species in one step or feed early colonizers. This predicted importance of host feeding is supported by published data on the impacts of breast milk in the assembly of the human microbiome. We conclude that both microbe to microbe and host to microbe interactions are important for the trajectory of microbiome assembly.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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