Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis

Das, Nupur K.; Schwartz, Andrew J.; Barthel, Gabrielle; Inohara, Naohiro; Liu, Qing; Sankar, Amanda; Hill, David R.; Ma, Xiaoya; Lamberg, Olivia; Schnizlein, Matthew K.; Arqués, Juan Luís; Spence, Jason R.; Núñez, Gabriel; Patterson, Andrew D.; Sun, Duxin; Young, Vincent B.; Shah, Yatrik M.

doi:10.1016/j.cmet.2019.10.005

Cited by 212 publications

(201 citation statements)

References 59 publications

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“…This further induces oxidative stress, lipid metabolism dysbiosis, low‐grade inflammation, and cell toxicity. In addition, diet‐induced differentially microbial metabolites (e.g., short‐chain fatty acids) further stimulate proliferation of enterocytes, expand surface area of the absorptive cells, and upregulate gene expression involving mineral‐transport proteins [ 60 ] and inflammatory response related to innate immune function. At the same time, genes related to cell cycle, proliferation, and apoptosis could be perturbed, which is critical for cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Pork Meat Proteins Alter Gut Microbiota and Lipid Metabolism Genes in the Colon of Adaptive Immune‐Deficient Mice

Zhang

Zou

Zhao

et al. 2020

Molecular Nutrition Food Res

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Scope: Excessive consumption of processed meat has been linked to an increasing risk of gut diseases. It is investigated how pork meat proteins affect colon homeostasis between normal and immune-compromised mice. Methods and results: Immune-deficient mice (Rag1 −/− ) and wild-type mice are fed a diet that contains 20% casein or protein isolated from cooked pork or dry-cured pork for 3 months. Rag1 −/− mice show greater variations in transcriptome responses and higher microbial diversity than wild-type mice after consumption of the pork meat protein diets. Intake of pork meat protein diets also increases body weight and induces colonic oxidative stress, low-grade inflammation, and gene expression involved in immune function, cell cycle, and migration. Key genes like Hmox1, Ppara, and Pparg are highly upregulated by pork meat protein. These changes are associated with decreased abundances of Blautia, Bifidobacterium, and Alistipes and increased abundances of Akkermansia muciniphila and Ruminococcaceae. Conclusion: Pork meat proteins affect colon health in both wild-type and Rag1 −/− mice by altering the microbiome profile under the complex interaction with adaptive immunity. The findings herein give a new insight into the understanding of meat intake, immunity, and gut health.

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Section: Discussionmentioning

confidence: 99%

Pork Meat Proteins Alter Gut Microbiota and Lipid Metabolism Genes in the Colon of Adaptive Immune‐Deficient Mice

Zhang

Zou

Zhao

et al. 2020

Molecular Nutrition Food Res

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“…165 Conversely, when placed on a low-iron diet, germ-free mice exhibited milder iron-deficiency-induced anaemia, perhaps suggesting more efficient iron uptake in the absence of competing microbiota. 166 The gut microbiota, specifically Lactobacillus sp., were found to reduce host iron uptake through the production of small molecule metabolites, including the 1,3-diaminopropane, which inhibited HIF2a and expression of iron uptake proteins in the enterocyte. 1,3-Diaminopropane production by lactobacilli was specifically enhanced during dietary iron deficiency, highlighting how the microbiota modulates local host iron homeostasis and luminal iron availability.…”

Section: Gut Microbiota Modulates Iron Uptake and Systemic Iron Homeomentioning

confidence: 99%

“…1,3-Diaminopropane production by lactobacilli was specifically enhanced during dietary iron deficiency, highlighting how the microbiota modulates local host iron homeostasis and luminal iron availability. 166 Mouse models also suggest that, through its capacity to modulate systemic inflammatory responses, the gut microbiota can determine the extent of hepcidin induction and systemic hypoferraemia. 167 Commensal gut microbiota and iron acquisition by pathogenic microorganisms…”

Section: Gut Microbiota Modulates Iron Uptake and Systemic Iron Homeomentioning

confidence: 99%

“…149,176 Targeting the host Probiotics and prebiotics may be useful in the treatment of iron deficiency and iron overload, by altering bioavailability of iron in the gastrointestinal tract and iron uptake by the enterocyte. 166,[177][178][179] Furthermore, dysbiosis in gastrointestinal and systemic auto-inflammatory disorders may in turn influence systemic iron metabolism, contributing to the anaemia of inflammation and functional iron deficiency commonly observed in these conditions. 151,167,180 On the flip side, the potential for dysbiosis driven by dietary iron supplementation, thus exacerbating disease, complicates the treatment of anaemia in inflammatory bowel disease patients.…”

Section: Targeting the Pathogenmentioning

confidence: 99%

“…188,189 Conversely, iron-deficient diets in experimental systems seem to favour the growth of protective microorganisms. 107,166…”

Section: Targeting the Pathogenmentioning

confidence: 99%

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The battle for iron in enteric infections

et al. 2020

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Iron is an essential element for almost all living organisms, but can be extremely toxic in high concentrations. All organisms must therefore employ homeostatic mechanisms to finely regulate iron uptake, usage and storage in the face of dynamic environmental conditions. The critical step in mammalian systemic iron homeostasis is the fine regulation of dietary iron absorption. However, as the gastrointestinal system is also home to >10 14 bacteria, all of which engage in their own programmes of iron homeostasis, the gut represents an anatomical location where the interkingdom fight for iron is never-ending. Here, we explore the molecular mechanisms of, and interactions between, host and bacterial iron homeostasis in the gastrointestinal tract. We first detail how mammalian systemic and cellular iron homeostasis influences gastrointestinal iron availability. We then focus on two important human pathogens, Salmonella and Clostridia; despite their differences, they exemplify how a bacterial pathogen must navigate and exploit this web of iron homeostasis interactions to avoid host nutritional immunity and replicate successfully. We then reciprocally explore how iron availability interacts with the gastrointestinal microbiota, and the consequences of this on mammalian physiology and pathogen iron acquisition. Finally, we address how understanding the battle for iron in the gastrointestinal tract might inform clinical practice and inspire new treatments for important diseases.

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Essential Nutrients and the Microbiota

2023

Small Animal Microbiomes and Nutrition

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Microbial Metabolite Signaling Is Required for Systemic Iron Homeostasis

Cited by 212 publications

References 59 publications

Pork Meat Proteins Alter Gut Microbiota and Lipid Metabolism Genes in the Colon of Adaptive Immune‐Deficient Mice

Pork Meat Proteins Alter Gut Microbiota and Lipid Metabolism Genes in the Colon of Adaptive Immune‐Deficient Mice

The battle for iron in enteric infections

Essential Nutrients and the Microbiota

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