Gut Microbial Influences on the Mammalian Intestinal Stem Cell Niche

The mammalian intestinal epithelial stem cell (IESC) niche is comprised of diverse epithelial, immune, and stromal cells, which together respond to environmental changes within the lumen and exert coordinated regulation of IESC behavior. There is growing appreciation for the role of the gut microbiota in modulating intestinal proliferation and differentiation, as well as other aspects of intestinal physiology. In this review, we evaluate the diverse roles of known niche cells in responding to gut microbiota and supporting IESCs. Furthermore, we discuss the potential mechanisms by which microbiota may exert their influence on niche cells and possibly on IESCs directly. Finally, we present an overview of the benefits and limitations of available tools to study niche-microbe interactions and provide our recommendations regarding their use and standardization. The study of host-microbe interactions in the gut is a rapidly growing field, and the IESC niche is at the forefront of host-microbe activity to control nutrient absorption, endocrine signaling, energy homeostasis, immune response, and systemic health.

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Host-microbe interactions mediating antitumorigenic effects of MRX0518, a gut microbiota-derived bacterial strain, in breast, renal and lung carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e15006 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e15006-e15006 ◽

Cited By ~ 3

Author(s):

Alex Stevenson ◽

Alessio Panzica ◽

Amy Holt ◽

Delphine Laute Caly ◽

Anna Ettore ◽

...

Keyword(s):

Gut Microbiota ◽

Lung Carcinoma ◽

Bacterial Strain ◽

Microbe Interactions ◽

Host Microbe Interactions

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Scap and the intestinal epithelial stem cell niche: new insights from lipid biology

The Journal of Lipid Research ◽

10.1194/jlr.c061309 ◽

2015 ◽

Vol 56 (8) ◽

pp. 1381-1382 ◽

Cited By ~ 2

Author(s):

Matthew A. Ciorba

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Intestinal Epithelial ◽

Epithelial Stem Cell ◽

Cell Niche

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Smooth muscle-specific MMP17 (MT4-MMP) regulates the intestinal stem cell niche and regeneration after damage

Nature Communications ◽

10.1038/s41467-021-26904-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Mara Martín-Alonso ◽

Sharif Iqbal ◽

Pia M. Vornewald ◽

Håvard T. Lindholm ◽

Mirjam J. Damen ◽

...

Keyword(s):

Smooth Muscle ◽

Stem Cell ◽

Smooth Muscle Cells ◽

Stem Cell Niche ◽

Muscle Cells ◽

Intestinal Stem Cell ◽

Matricellular Protein ◽

Intestinal Epithelial ◽

Epithelial Regeneration ◽

Cell Niche

AbstractSmooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle cells may have. Here, we show that smooth muscle cells may be the dominant suppliers of BMP antagonists, which are niche factors essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the membrane-bound matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle cells, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we propose that MMP17 affects intestinal epithelial reprogramming after damage indirectly by cleaving diffusible factor(s) such as the matricellular protein PERIOSTIN. Together, we identify an important signaling axis that establishes a role for smooth muscle cells as modulators of intestinal epithelial regeneration and the intestinal stem cell niche.

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Smooth muscle-specific MMP17 (MT4-MMP) defines the intestinal ECM niche

10.1101/2020.06.18.147769 ◽

2020 ◽

Author(s):

Mara Martín-Alonso ◽

Håvard T. Lindholm ◽

Sharif Iqbal ◽

Pia Vornewald ◽

Sigrid Hoel ◽

...

Keyword(s):

Smooth Muscle ◽

Stem Cell ◽

Intestinal Stem Cell ◽

Matricellular Protein ◽

Intestinal Epithelial ◽

Stem Cell Maintenance ◽

Epithelial Regeneration ◽

The Matrix ◽

Signaling Axis ◽

Cell Niche

SUMMARYSmooth muscle is an essential component of the intestine, both to maintain its structure and produce peristaltic and segmentation movements. However, very little is known about other putative roles that smooth muscle may have. Here, we show that smooth muscle is the dominant supplier of BMP antagonists, which are niche factors that are essential for intestinal stem cell maintenance. Furthermore, muscle-derived factors can render epithelium reparative and fetal-like, which includes heightened YAP activity. Mechanistically, we find that the matrix metalloproteinase MMP17, which is exclusively expressed by smooth muscle, is required for intestinal epithelial repair after inflammation- or irradiation-induced injury. Furthermore, we provide evidence that MMP17 affects intestinal epithelial reprogramming indirectly by cleaving the matricellular protein PERIOSTIN, which itself is able to activate YAP. Together, we identify an important signaling axis that firmly establishes a role for smooth muscle as a modulator of intestinal epithelial regeneration and the intestinal stem cell niche.

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Adaptation of the Gut Microbiota to Modern Dietary Sugars and Sweeteners

Advances in Nutrition ◽

10.1093/advances/nmz118 ◽

2019 ◽

Vol 11 (3) ◽

pp. 616-629 ◽

Cited By ~ 8

Author(s):

Sara C Di Rienzi ◽

Robert A Britton

Keyword(s):

Gut Microbiota ◽

Intestinal Tract ◽

Western Diet ◽

Health Concerns ◽

Diet Cost ◽

Microbe Interactions ◽

Novel Approaches ◽

Host Microbe Interactions ◽

Genetic Profiles ◽

Dietary Sugars

ABSTRACT The consumption of sugar has become central to the Western diet. Cost and health concerns associated with sucrose spurred the development and consumption of other sugars and sweeteners, with the average American consuming 10 times more sugar than 100 y ago. In this review, we discuss how gut microbes are affected by changes in the consumption of sugars and other sweeteners through transcriptional, abundance, and genetic adaptations. We propose that these adaptations result in microbes taking on different metabolic, ecological, and genetic profiles along the intestinal tract. We suggest novel approaches to assess the consequences of these changes on host–microbe interactions to determine the safety of novel sugars and sweeteners.

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Faculty Opinions recommendation of Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1163398.625117 ◽

2009 ◽

Author(s):

Frank Seeber

Keyword(s):

Stem Cell ◽

Stem Cell Niche ◽

Intestinal Epithelial ◽

Epithelial Culture ◽

Cell Niche

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Gut Microbiota and Iron: The Crucial Actors in Health and Disease

Pharmaceuticals ◽

10.3390/ph11040098 ◽

2018 ◽

Vol 11 (4) ◽

pp. 98 ◽

Cited By ~ 44

Author(s):

Bahtiyar Yilmaz ◽

Hai Li

Keyword(s):

Gut Microbiota ◽

Inflammatory Diseases ◽

Life Forms ◽

Iron Availability ◽

Human Beings ◽

Human Gastrointestinal Tract ◽

Dynamic Modulation ◽

Microbe Interactions ◽

Health And Disease ◽

Host Microbe Interactions

Iron (Fe) is a highly ample metal on planet earth (~35% of the Earth’s mass) and is particularly essential for most life forms, including from bacteria to mammals. Nonetheless, iron deficiency is highly prevalent in developing countries, and oral administration of this metal is so far the most effective treatment for human beings. Notably, the excessive amount of unabsorbed iron leave unappreciated side effects at the highly interactive host–microbe interface of the human gastrointestinal tract. Recent advances in elucidating the molecular basis of interactions between iron and gut microbiota shed new light(s) on the health and pathogenesis of intestinal inflammatory diseases. We here aim to present the dynamic modulation of intestinal microbiota by iron availability, and conversely, the influence on dietary iron absorption in the gut. The central part of this review is intended to summarize our current understanding about the effects of luminal iron on host–microbe interactions in the context of human health and disease.

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Insulin/IGF-1 enhances intestinal epithelial crypt proliferation through PI3K/Akt, and not ERK signaling in obese humans

Experimental Biology and Medicine ◽

10.1177/1535370218785152 ◽

2018 ◽

Vol 243 (11) ◽

pp. 911-916 ◽

Cited By ~ 3

Author(s):

Weinan Zhou ◽

Blair M Rowitz ◽

Megan J Dailey

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Growth Factor ◽

Insulin Like Growth Factor ◽

Intestinal Epithelial ◽

Receptor Signaling ◽

Epithelial Stem Cells ◽

Cell Niche ◽

And Function ◽

Abnormal Tissue

The intestinal epithelium is continuously regenerated through proliferation and differentiation of stem cells located in the intestinal crypts. Obesity affects this process and results in greater stem cell proliferation and altered tissue growth and function. Obesity-induced high levels of insulin and insulin-like growth factor-1 in the stem cell niche are found to impact proliferation in rodents indicating that insulin and insulin-like growth factor-1 receptors may play a role in modulating intestinal epithelial stem cell proliferation. To determine whether insulin or insulin-like growth factor-1 can induce proliferation in human intestinal epithelial stem cells, and if two downstream insulin and insulin-like growth factor-1 receptor signaling pathways, PI3K/Akt and ERK, are involved, we used primary small intestinal epithelial crypts isolated from obese humans and investigated (1) the effect of insulin or insulin-like growth factor-1 on crypt proliferation, and (2) the effect of insulin and insulin-like growth factor-1 signaling inhibitors on insulin or insulin-like growth factor-1-induced proliferation. We found that insulin and insulin-like growth factor-1 enhanced the proliferation of crypt cells, including intestinal epithelial stem cells. Inhibition of the PI3K/Akt pathway attenuated insulin and insulin-like growth factor-1-induced proliferation, but inhibition of the ERK pathway had no effect. These results suggest that the classical metabolic PI3K pathway and not the canonical proliferation ERK pathway is involved in the insulin/insulin-like growth factor-1-induced increase in crypt proliferation in obese humans, which may contribute to abnormal tissue renewal and function. Impact statement This study investigates if insulin or insulin-like growth factor-1 (IGF-1) induces intestinal epithelial proliferation in humans, and if insulin and IGF-1 receptor signaling is involved in this process in obesity. Although obesity-induced high levels of insulin and IGF-1 in the stem cell niche are found to impact the proliferation of intestinal epithelial stem cells in rodents, we are the first to investigate this effect in humans. We found that insulin and IGF-1 enhanced the proliferation of intestinal crypts (including stem cells and other crypt cells) isolated from obese humans, and PI3K/Akt, and not ERK signaling was involved in insulin or IGF-1-induced proliferation. The imbalance in signaling between PI3K/Akt and ERK pathways may point to a pathway-specific impairment in insulin/IGF-1 receptor signaling. We propose that this may contribute to reciprocal relationships between insulin/IGF-1 receptor resistance and intestinal epithelial proliferation that leads to abnormal tissue renewal and function.

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Gut Microbiota and Mucosal Immunity in the Neonate

Medical Sciences ◽

10.3390/medsci6030056 ◽

2018 ◽

Vol 6 (3) ◽

pp. 56 ◽

Cited By ~ 19

Author(s):

Majda Dzidic ◽

Alba Boix-Amorós ◽

Marta Selma-Royo ◽

Alex Mira ◽

Maria Collado

Keyword(s):

Immune System ◽

Gut Microbiota ◽

System Response ◽

Delivery Mode ◽

Complex Dynamic ◽

Close Relationship ◽

Gut Immunity ◽

Microbe Interactions ◽

Immune System Response ◽

Host Microbe Interactions

Gut microbiota colonization is a complex, dynamic, and step-wise process that is in constant development during the first years of life. This microbial settlement occurs in parallel with the maturation of the immune system, and alterations during this period, due to environmental and host factors, are considered to be potential determinants of health-outcomes later in life. Given that host–microbe interactions are mediated by the immune system response, it is important to understand the close relationship between immunity and the microbiota during birth, lactation, and early infancy. This work summarizes the evidence to date on early gut microbiota colonization, and how it influences the maturation of the infant immune system and health during the first 1000 days of life. This review will also address the influence of perinatal antibiotic intake and the importance of delivery mode and breastfeeding for an appropriate development of gut immunity.

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