Browse
Submit Data
Databases
API
Help

Dataset Information

4 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Microbiota regulates the turnover kinetics of gut macrophages in health and inflammation

ABSTRACT: Maintenance of the gut lamina propria–resident macrophage cell pool requires monocyte input during adulthood. Here, Ruedl and colleagues demonstrate that the intestinal microbiome positively influences the replenishment of tissue-resident macrophages under both steady-state and inflammatory conditions. The gut immune system has evolved to co-exist in a mutually beneficial symbiotic relationship with its microflora. Here, using a germ-free fate-mapping mouse model, we provide clear insight into how the enteric commensals determine the kinetics of macrophage turnover. The microbiome density along the gastrointestinal tract defines the persistence of ontogenically diverse macrophages, with the highest numbers of the long-lived F4/80hiTim4+ macrophage subset in the less densely colonized small intestine. Furthermore, the microbiome contributes to a tightly regulated monocyte-dependent replenishment of both long- and short-lived F4/80hi macrophages under homeostatic and inflammatory conditions. In the latter situation, the commensals regulate rapid replenishment of the depleted macrophage niche caused by the intestinal inflammation. The microbial ecosystem imprints a favorable cytokine microenvironment in the intestine to support macrophage survival and monocyte-dependent replenishment. Therefore, the host immune system-commensal cross-talk provides an efficient strategy to assure intestinal homeostasis.

SUBMITTER: Chen Q

PROVIDER: S-EPMC8572849 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Bugging inflammation: role of the gut microbiota.

Project description:The advent of vaccination and improved hygiene have eliminated many of the deadly infectious pathogens in developed nations. However, the incidences of inflammatory diseases, such as inflammatory bowel disease, asthma, obesity and diabetes are increasing dramatically. Research in the recent decades revealed that it is indeed the lack of early childhood microbial exposure, increase use of antibiotics, as well as increase consumption of processed foods high in carbohydrates and fats, and lacking fibre, which wreak havoc on the proper development of immunity and predispose the host to elevated inflammatory conditions. Although largely unexplored and under-appreciated until recent years, these factors impact significantly on the composition of the gut microbiota (a collection of microorganisms that live within the host mucosal tissue) and inadvertently play intricate and pivotal roles in modulating an appropriate host immune response. The suggestion that shifts in the composition of host microbiota is a risk factor for inflammatory disease raises an exciting opportunity whereby the microbiota may also present as a potential modifiable component or therapeutic target for inflammatory diseases. This review provides insights into the interactions between the microbiota and the immune system, how these affect disease phenotypes, and explore current and emerging therapies that target the gut microbiota as potential treatment for inflammatory diseases.

| S-EPMC4855262 | biostudies-other

Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages.

Project description:A lacteal is a blunt-ended, long, tube-like lymphatic vessel located in the center of each intestinal villus that provides a unique route for drainage of absorbed lipids from the small intestine. However, key regulators for maintaining lacteal integrity are poorly understood. Here, we explore whether and how the gut microbiota regulates lacteal integrity. Germ depletion by antibiotic treatment triggers lacteal regression during adulthood and delays lacteal maturation during the postnatal period. In accordance with compromised lipid absorption, the button-like junction between lymphatic endothelial cells, which is ultrastructurally open to permit free entry of dietary lipids into lacteals, is significantly reduced in lacteals of germ-depleted mice. Lacteal defects are also found in germ-free mice, but conventionalization of germ-free mice leads to normalization of lacteals. Mechanistically, VEGF-C secreted from villus macrophages upon MyD88-dependent recognition of microbes and their products is a main factor in lacteal integrity. Collectively, we conclude that the gut microbiota is a crucial regulator for lacteal integrity by endowing its unique microenvironment and regulating villus macrophages in small intestine.

| S-EPMC6446200 | biostudies-literature

Lactoferrin Alleviates Inflammation and Regulates Gut Microbiota Composition in H5N1-Infected Mice.

Project description:The impact of lactoferrin, an antimicrobial peptide (AMP) with iron-binding properties, on the intestinal barrier and microflora of mice infected with highly pathogenic avian influenza A (H5N1) virus remains unclear. To investigate the effects of lactoferrin on the histopathology and intestinal microecological environment, we conducted a study using H5N1-infected mice. H5N1 infection resulted in pulmonary and intestinal damage, as well as an imbalance in gut microbiota, significantly increasing the abundance of pathogenic bacteria such as Helicobacter pylori and Campylobacter. The consumption of lactoferrin in the diet alleviated lung injury and restored the downregulation of the INAVA gene and intestinal dysfunction caused by H5N1 infection. Lactoferrin not only reduced lung and intestinal injury, but also alleviated inflammation and reversed the changes in intestinal microflora composition while increasing the abundance of beneficial bacteria. Moreover, lactoferrin rebalanced the gut microbiota and partially restored intestinal homeostasis. This study demonstrated that lactoferrin exerts its effects on the intestinal tract, leading to improvements in gut microbiota and restoration of the integrity of both the intestinal wall and lung tissue. These findings support the notion that lactoferrin may be a promising candidate for systemic treatment of influenza by locally acting on the intestine and microbiota.

| S-EPMC10421285 | biostudies-literature

Turnover Kinetics of Pancreatic Macrophages in Lean and Obese Diabetic Mice.

Project description:Pancreatic resident macrophages, a heterogeneous family of cells with distinct origins and phenotypes, are the main myeloid cells in exocrine and endocrine tissues. Adult exocrine F4/80hi macrophages consist of three different subsets based on the embryonic marker Tim-4 and MHC II expression. Their frequencies shift during aging and obesity with the Tim-4-MHCII+ fraction becoming the predominant subpopulation in the inter acinar stroma. Endocrine resident F4/80hi macrophages are more homogenous and represent the prevalent leukocyte fraction residing within the islets in both lean and obese mice. We used an adult fate mapping mouse model to characterize turnover kinetics within the pancreatic resident macrophages under normal homeostasis and obese diabetic conditions. We demonstrate that islet resident macrophages show unique replenishment kinetics, with embryonic macrophages being gradually replaced by bone marrow-derived monocytes with increasing age. Their replenishment was independent of the CCL2/CCR2 axis. Furthermore, we confirmed that both exocrine Tim-4+MHCIIlow and Tim-4+MHCII+ fractions are long-lived and primarily independent from bone marrow-derived monocytes. In contrast, exocrine Tim-4-MHCII+ macrophages are gradually replaced through a CCR2-dependent influx of bone marrow-derived monocytes in aging. Moreover, we show that obesity and type 2 diabetes do not affect the turnover kinetics of any macrophage subpopulation residing in the pancreas. Our study uncovers new insights on pancreatic macrophage biology in aging and obesity.

| S-EPMC9326506 | biostudies-literature

Gut microbiota, inflammation and colorectal cancer.

Project description:Although genes contribute to colorectal cancer, the gut microbiota are an important player. Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression. A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated. Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer. In the current review, we discuss the novel roles of microbiota in the progression of colon cancer. Although microbiota technically include organisms other than bacteria e.g., viruses and fungi, this review will primarily focus on bacteria. We summarize epidemiological studies of human microbiome and colon cancer. We discuss the progress in the scientific understanding of the interplay between the gut microbiota, barrier function, and host responses in experimental models. Further, we discuss the potential application in prevention, diagnosis, and therapy of colon cancer by targeting microbiota. We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application.

| S-EPMC5221561 | biostudies-literature

Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity.

Project description:White adipose tissue (WAT) inflammation contributes to the development of insulin resistance in obesity. While the role of adipose tissue macrophage (ATM) pro-inflammatory signalling in the development of insulin resistance has been established, it is less clear how WAT inflammation is initiated. Here, we show that ATMs isolated from obese mice and humans exhibit markers of increased rate of de novo phosphatidylcholine (PC) biosynthesis. Macrophage-specific knockout of phosphocholine cytidylyltransferase A (CCTα), the rate-limiting enzyme of de novo PC biosynthesis pathway, alleviated obesity-induced WAT inflammation and insulin resistance. Mechanistically, CCTα-deficient macrophages showed reduced ER stress and inflammation in response to palmitate. Surprisingly, this was not due to lower exogenous palmitate incorporation into cellular PCs. Instead, CCTα-null macrophages had lower membrane PC turnover, leading to elevated membrane polyunsaturated fatty acid levels that negated the pro-inflammatory effects of palmitate. Our results reveal a causal link between obesity-associated increase in de novo PC synthesis, accelerated PC turnover and pro-inflammatory activation of ATMs.

| S-EPMC6748830 | biostudies-literature

The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs.

Project description:The gut microbiota is a key environmental determinant of mammalian metabolism. Regulation of white adipose tissue (WAT) by the gut microbiota is a process critical to maintaining metabolic fitness, and gut dysbiosis can contribute to the development of obesity and insulin resistance (IR). However, how the gut microbiota regulates WAT function remains largely unknown. Here, we show that tryptophan-derived metabolites produced by the gut microbiota controlled the expression of the miR-181 family in white adipocytes in mice to regulate energy expenditure and insulin sensitivity. Moreover, dysregulation of the gut microbiota-miR-181 axis was required for the development of obesity, IR, and WAT inflammation in mice. Our results indicate that regulation of miR-181 in WAT by gut microbiota-derived metabolites is a central mechanism by which host metabolism is tuned in response to dietary and environmental changes. As we also found that MIR-181 expression in WAT and the plasma abundance of tryptophan-derived metabolites were dysregulated in a cohort of obese human children, the MIR-181 family may represent a potential therapeutic target to modulate WAT function in the context of obesity.

| S-EPMC7050429 | biostudies-literature

Bazedoxifene and conjugated estrogen combination improves gut-liver axis health [microbiota]

Project description:Bazedoxifene and conjugated estrogens (CE+BZA) combination has been shown to prevent visceral adiposity and weight gain after menopause. However, its interaction with the microbiota has yet to be examined. In the present study, we use several –omics technologies to characterize the effects of various estrogens on the health of gut-liver axis. As reported in previous studies, CE+BZA combination is very effective at preventing ovariectomy-induced weight gain in mice fed a high-fat diet. Additionally, CE+BZA induces unique liver transcriptomic and blood metabolite profiles compared to estradiol, conjugated estrogens alone, and bazedoxifene alone. Several pathways and metabolites influenced are associated with lower rates of inflammation and overall benefits to gut and liver health. Finally, microbiome analysis shows that several bacterial species that potentially metabolize estrogens and affect their half-life in the body were significantly changed in CE+BZA treated mice. Our findings indicate a possible link between certain estrogens and gut microbiome and suggest a metabolic benefit of estrogens through manipulation of the gut-liver axis.

2019-12-28 | GSE93096 | GEO

The gut microbiota and host health: a new clinical frontier.

Project description:Over the last 10-15?years, our understanding of the composition and functions of the human gut microbiota has increased exponentially. To a large extent, this has been due to new 'omic' technologies that have facilitated large-scale analysis of the genetic and metabolic profile of this microbial community, revealing it to be comparable in influence to a new organ in the body and offering the possibility of a new route for therapeutic intervention. Moreover, it might be more accurate to think of it like an immune system: a collection of cells that work in unison with the host and that can promote health but sometimes initiate disease. This review gives an update on the current knowledge in the area of gut disorders, in particular metabolic syndrome and obesity-related disease, liver disease, IBD and colorectal cancer. The potential of manipulating the gut microbiota in these disorders is assessed, with an examination of the latest and most relevant evidence relating to antibiotics, probiotics, prebiotics, polyphenols and faecal microbiota transplantation.

| S-EPMC4752653 | biostudies-other

Gut microbiota regulates blood-cerebrospinal fluid barrier function and Aβ pathology

Project description:Accumulating evidence indicates that gut microbiota dysbiosis is associated with increased blood-brain barrier (BBB) permeability and contributes to Alzheimer's disease (AD) pathogenesis. In contrast, the influence of gut microbiota on the blood-cerebrospinal fluid (CSF) barrier has not yet been studied. Here, we report that mice lacking gut microbiota display increased blood-CSF barrier permeability associated with disorganized tight junctions (TJs), which can be rescued by recolonization with gut microbiota or supplementation with short-chain fatty acids (SCFAs). Our data reveal that gut microbiota is important not only for the establishment, but also for the maintenance, of a tight barrier. Also, we report that the vagus nerve plays an important role in this process and that SCFAs can independently tighten the barrier. Administration of SCFAs in AppNL-G-F mice improved the subcellular localization of TJs in the blood-CSF barrier, reduced the β-amyloid (Aβ) burden, and affect microglial phenotype. Altogether, our results suggest that modulating the microbiota and administering SCFAs might have therapeutic potential in AD via blood-CSF barrier tightening and maintaining microglial activity and Aβ clearance.

| S-SCDT-10_15252-EMBJ_2022111515 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data