The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

Diurnal (i.e., 24-hour) oscillations of the gut microbiome have been described in various species including mice and humans. However, the driving force behind these rhythms remains less clear. In this study, we differentiate between endogenous and exogenous time cues driving microbial rhythms. Our results demonstrate that fecal microbial oscillations are maintained in mice kept in the absence of light, supporting a role of the hosts circadian system rather than representing a diurnal response to environmental changes. Intestinal epithelial cell-specific ablation of the core clock gene Bmal1 disrupts rhythmicity of microbiota. Targeted metabolomics functionally link intestinal clock-controlled bacteria to microbial-derived products, in particular branched-chain fatty acids and secondary bile acids. Microbiota transfer from intestinal clock-deficient mice into germ-free mice altered intestinal gene expression, enhanced lymphoid organ weights and suppressed immune cell recruitment. These results highlight the importance of functional intestinal clocks for circadian microbiota composition and function, which is required to balance the hosts gastrointestinal homeostasis.

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Inflammation in Periodontal Disease: Possible Link to Vascular Disease

Frontiers in Physiology ◽

10.3389/fphys.2020.609614 ◽

2021 ◽

Vol 11 ◽

Author(s):

Oindrila Paul ◽

Payal Arora ◽

Michael Mayer ◽

Shampa Chatterjee

Keyword(s):

Periodontal Disease ◽

Bacterial Infections ◽

Immune Cell ◽

Epidemiological Data ◽

Cell Recruitment ◽

Periodontal Inflammation ◽

Tissue Healing ◽

And Function ◽

Immune Cell Recruitment

Inflammation is a well-organized protective response to pathogens and consists of immune cell recruitment into areas of infection. Inflammation either clears pathogens and gets resolved leading to tissue healing or remains predominantly unresolved triggering pathological processes in organs. Periodontal disease (PD) that is initiated by specific bacteria also triggers production of inflammatory mediators. These processes lead to loss of tissue structure and function. Reactive oxygen species and oxidative stress play a role in susceptibility to periodontal pathogenic bacterial infections. Periodontal inflammation is a risk factor for systemic inflammation and eventually cardiovascular disease (CVD). This review discusses the role of inflammation in PD and its two way association with other health conditions such as diabetes and CVD. Some of the mechanisms underpinning the links between inflammation, diabetes, CVD and PD are also discussed. Finally, we review available epidemiological data and other reports to assess possible links between oral health and CVD.

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Antioxidant Vitamins and Prebiotic FOS and XOS Differentially Shift Microbiota Composition and Function and Improve Intestinal Epithelial Barrier In Vitro

Nutrients ◽

10.3390/nu13041125 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1125

Author(s):

Van T. Pham ◽

Marta Calatayud ◽

Chloë Rotsaert ◽

Nicole Seifert ◽

Nathalie Richard ◽

...

Keyword(s):

Gut Microbiota ◽

Microbial Activity ◽

Intestinal Barrier ◽

Antioxidant Vitamin ◽

Intestinal Epithelial ◽

Microbiota Composition ◽

Branched Chain Fatty Acids ◽

Branched Chain ◽

And Function

Human gut microbiota (HGM) play a significant role in health and disease. Dietary components, including fiber, fat, proteins and micronutrients, can modulate HGM. Much research has been performed on conventional prebiotics such as fructooligosaccharides (FOS) and galactooligosaccharides (GOS), however, novel prebiotics or micronutrients still require further validation. We assessed the effect of FOS, xylooligosaccharides (XOS) and a mixture of an antioxidant vitamin blend (AOB) on gut microbiota composition and activity, and intestinal barrier in vitro. We used batch fermentations and tested the short-term effect of different products on microbial activity in six donors. Next, fecal inocula from two donors were used to inoculate the simulator of the human microbial ecosystem (SHIME) and after long-term exposure of FOS, XOS and AOB, microbial activity (short- and branched-chain fatty acids and lactate) and HGM composition were evaluated. Finally, in vitro assessment of intestinal barrier was performed in a Transwell setup of differentiated Caco-2 and HT29-MTX-E12 cells exposed to fermentation supernatants. Despite some donor-dependent differences, all three tested products showed beneficial modulatory effects on microbial activity represented by an increase in lactate and SCFA levels (acetate, butyrate and to a lesser extent also propionate), while decreasing proteolytic markers. Bifidogenic effect of XOS was consistent, while AOB supplementation appears to exert a specific impact on reducing F. nucleatum and increasing butyrate-producing B. wexlerae. Functional and compositional microbial changes were translated to an in vitro host response by increases of the intestinal barrier integrity by all the products and a decrease of the redox potential by AOB supplementation.

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Role of Branched-Chain Fatty Acids in pH Stress Tolerance in Listeria monocytogenes

Applied and Environmental Microbiology ◽

10.1128/aem.00865-06 ◽

2006 ◽

Vol 73 (3) ◽

pp. 997-1001 ◽

Cited By ~ 84

Author(s):

Efstathios S. Giotis ◽

David A. McDowell ◽

Ian S. Blair ◽

Brian J. Wilkinson

Keyword(s):

Fatty Acids ◽

Listeria Monocytogenes ◽

Stress Tolerance ◽

Ph Sensitive ◽

Branched Chain Fatty Acids ◽

Alkaline Conditions ◽

Branched Chain ◽

Ph Adaptation ◽

Chain Fatty Acids

ABSTRACT In alkaline conditions, Listeria monocytogenes cells develop higher proportions of branched-chain fatty acids (FAs), including more anteiso forms. In acid conditions, the opposite occurs. Reduced growth of pH-sensitive mutants at adverse pH (5.0/9.0) was alleviated by the addition of 2-methylbutyrate (an anteiso-FA precursor), suggesting that anteiso-FAs are important in adaptation to adverse pH. The balance between anteiso- and iso-FAs may be more important than changes in the amounts and/or degrees of saturation of FAs in pH adaptation.

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Nonneuronal Cholinergic System in Breast Tumors and Dendritic Cells: Does It Improve or Worsen the Response to Tumor?

ISRN Cell Biology ◽

10.1155/2013/486545 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12

Author(s):

Marisa Vulcano ◽

María Gabriela Lombardi ◽

María Elena Sales

Keyword(s):

Dendritic Cells ◽

Cholinergic System ◽

Parasympathetic Nervous System ◽

Immune Cell ◽

Breast Tumors ◽

Cell Types ◽

Cellular Functions ◽

And Migration ◽

And Function

Besides being the main neurotransmitter in the parasympathetic nervous system, acetylcholine (ACh) can act as a signaling molecule in nonneuronal tissues. For this reason, ACh and the enzymes that synthesize and degrade it (choline acetyltransferase and acetylcholinesterase) as well as muscarinic (mAChRs) and nicotinic receptors conform the non-neuronal cholinergic system (nNCS). It has been reported that nNCS regulates basal cellular functions including survival, proliferation, adhesion, and migration. Moreover, nNCS is broadly expressed in tumors and in different components of the immune system. In this review, we summarize the role of nNCS in tumors and in different immune cell types focusing on the expression and function of mAChRs in breast tumors and dendritic cells (DCs) and discussing the role of DCs in breast cancer.

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A functional spleen contributes to afucosylated IgG in humans

Scientific Reports ◽

10.1038/s41598-021-03196-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Iwona Wojcik ◽

David E. Schmidt ◽

Lisa A. de Neef ◽

Minke A. E. Rab ◽

Bob Meek ◽

...

Keyword(s):

Immune Responses ◽

Viral Infections ◽

Immune Cell ◽

Lymphoid Organ ◽

Immune Effector ◽

Adaptive Immune ◽

Wide Range ◽

Humoral Responses ◽

First Time

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.

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The Cutaneous Wound Innate Immunological Microenvironment

International Journal of Molecular Sciences ◽

10.3390/ijms21228748 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8748

Author(s):

Stephen Kirchner ◽

Vivian Lei ◽

Amanda S. MacLeod

Keyword(s):

Immune Response ◽

Wound Repair ◽

Immune Cell ◽

Skin Barrier ◽

Innate Immune ◽

Immune Microenvironment ◽

Cell Recruitment ◽

Adaptive Processes ◽

Immune Cell Recruitment

The skin represents the first line of defense and innate immune protection against pathogens. Skin normally provides a physical barrier to prevent infection by pathogens; however, wounds, microinjuries, and minor barrier impediments can present open avenues for invasion through the skin. Accordingly, wound repair and protection from invading pathogens are essential processes in successful skin barrier regeneration. To repair and protect wounds, skin promotes the development of a specific and complex immunological microenvironment within and surrounding the disrupted tissue. This immune microenvironment includes both innate and adaptive processes, including immune cell recruitment to the wound and secretion of extracellular factors that can act directly to promote wound closure and wound antimicrobial defense. Recent work has shown that this immune microenvironment also varies according to the specific context of the wound: the microbiome, neuroimmune signaling, environmental effects, and age play roles in altering the innate immune response to wounding. This review will focus on the role of these factors in shaping the cutaneous microenvironment and how this ultimately impacts the immune response to wounding.

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Long Noncoding RNA in Myeloid and Lymphoid Cell Differentiation, Polarization and Function

Cells ◽

10.3390/cells9020269 ◽

2020 ◽

Vol 9 (2) ◽

pp. 269 ◽

Cited By ~ 5

Author(s):

Imran Ahmad ◽

Araceli Valverde ◽

Fayek Ahmad ◽

Afsar Raza Naqvi

Keyword(s):

Cell Differentiation ◽

Immune Cells ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Immune Cell ◽

Lymphoid Cells ◽

Tissue Cell ◽

Specific Expression ◽

And Function

Long noncoding RNA (lncRNA) are a class of endogenous, non-protein coding RNAs that are increasingly being associated with various cellular functions and diseases. Yet, despite their ubiquity and abundance, only a minute fraction of these molecules has an assigned function. LncRNAs show tissue-, cell-, and developmental stage-specific expression, and are differentially expressed under physiological or pathological conditions. The role of lncRNAs in the lineage commitment of immune cells and shaping immune responses is becoming evident. Myeloid cells and lymphoid cells are two major classes of immune systems that work in concert to initiate and amplify innate and adaptive immunity in vertebrates. In this review, we provide mechanistic roles of lncRNA through which these noncoding RNAs can directly participate in the differentiation, polarization, and activation of myeloid (monocyte, macrophage, and dendritic cells) and lymphoid cells (T cells, B cells, and NK cells). While our knowledge on the role of lncRNA in immune cell differentiation and function has improved in the past decade, further studies are required to unravel the biological role of lncRNAs and identify novel mechanisms of lncRNA functions in immune cells. Harnessing the regulatory potential of lncRNAs can provide novel diagnostic and therapeutic targets in treating immune cell related diseases.

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