scholarly journals Systemic instruction of cell-mediated immunity by the intestinal microbiome

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1910 ◽  
Author(s):  
John Grainger ◽  
Rufus Daw ◽  
Kelly Wemyss

Recent research has shed light on the plethora of mechanisms by which the gastrointestinal commensal microbiome can influence the local immune response in the gut (in particular, the impact of the immune system on epithelial barrier homeostasis and ensuring microbial diversity). However, an area that is much less well explored but of tremendous therapeutic interest is the impact the gut microbiome has on systemic cell-mediated immune responses. In this commentary, we highlight some key studies that are beginning to broadly examine the different mechanisms by which the gastrointestinal microbiome can impact the systemic immune compartment. Specifically, we discuss the effects of the gut microbiome on lymphocyte polarisation and trafficking, tailoring of resident immune cells in the liver, and output of circulating immune cells from the bone marrow. Finally, we explore contexts in which this new understanding of long-range effects of the gut microbiome can have implications, including cancer therapies and vaccination.

2021 ◽  
Vol 8 ◽  
Author(s):  
Mahmoud A. Ghannoum ◽  
MaryKate Ford ◽  
Robert A. Bonomo ◽  
Ahmed Gamal ◽  
Thomas S. McCormick

The significant stressors brought about and exacerbated by COVID-19 are associated with startling surges in mental health illnesses, specifically those related to depressive disorders. Given the huge impact of depression on society, and an incomplete understanding of impactful therapeutics, we have examined the current literature surrounding the microbiome and gut-brain axis to advance a potential complementary approach to address depression and depressive disorders that have increased during the COVID-19 pandemic. While we understand that the impact of the human gut microbiome on emotional health is a newly emerging field and more research needs to be conducted, the current evidence is extremely promising and suggests at least part of the answer to understanding depression in more depth may lie within the microbiome. As a result of these findings, we propose that a microbiome-based holistic approach, which involves carefully annotating the microbiome and potential modification through diet, probiotics, and lifestyle changes, may address depression. This paper's primary purpose is to shed light on the link between the gut microbiome and depression, including the gut-brain axis and propose a holistic approach to microbiome modification, with the ultimate goal of assisting individuals to manage their battle with depression through diet, probiotics, and lifestyle changes, in addition to offering a semblance of hope during these challenging times.


2020 ◽  
Author(s):  
Piush Khanal ◽  
Christian Maltecca ◽  
Clint Schwab ◽  
Justin Fix ◽  
Francesco Tiezzi

Abstract BackgroundSwine gut microbiome constitutes a portion of the whole genome and has potential to affect different phenotypes. More recently, research is more directed towards association of gut microbiome and different traits in swine. However, the contribution of microbial composition to the phenotypic variation of meat quality and carcass composition traits in pigs has not been explored yet. The objectives of this study are to estimate the microbiabilities for different meat quality and carcass composition traits; to investigate the impact of intestinal microbiome on heritability estimates; to estimate the correlation between microbial diversity and meat quality and carcass composition traits; and to estimate the microbial correlation between the meat quality and carcass composition traits in a commercial swine population.ResultsThe contribution of the microbiome to carcass composition and meat quality traits was prominent although it varied over time, increasing from weaning to off test for most traits. Microbiability estimates of carcass composition traits were greater than that of meat quality traits. Among all of the traits analyzed, belly weight had higher microbiability estimate (0.29 ± 0.04). Adding microbiome information did not affect the estimates of genomic heritability of meat quality traits but affected the estimates of carcass composition traits. Fat depth had greater decrease (10%) in genomic heritability. High microbial correlations were found among several traits. This suggested that genomic correlation was partially contributed by genetic similarity of microbiome composition.ConclusionsResults indicate that better understanding of microbial composition could aid the improvement of complex traits, particularly the carcass composition traits in swine by inclusion of microbiome information in the genetic evaluation process.


2020 ◽  
Author(s):  
Thibault Scalvenzi ◽  
Isabelle Clavereau ◽  
Mickaël Bourge ◽  
Nicolas Pollet

AbstractBackgroundThe microorganism world living in amphibians is still largely under-represented and under-studied in the literature. Among anuran amphibians, African clawed frogs of the Xenopus genus stand as well-characterized models with an in-depth knowledge of their developmental biological processes including their metamorphosis. We used different approaches including flow cytometry and 16s rDNA gene metabarcoding to analyze the succession of microbial communities and their activities across different body habitats of Xenopus tropicalis. We used metagenomic and metatranscriptomic sequencing to evaluate the metabolic capacity of the premetamorphic tadpole’s gut microbiome.ResultsWe analyzed the bacterial components of the Xenopus gut microbiota, the adult gut biogeography, the succession of communities during ontogeny, the impact of the alimentation in shaping the tadpole’s gut bacterial communities, the transmission of skin and fecal bacteria to the eggs. We also identified the most active gut bacteria and their metabolic contribution to tadpole physiology including carbohydrate breakdown, nitrogen recycling, essential amino-acids and vitamin biosynthesis.ConclusionsWe present a comprehensive new microbiome dataset of a laboratory amphibian model. Our data provide evidences that studies on the Xenopus tadpole model can shed light on the interactions between a vertebrate host and its microbiome. We interpret our findings in light of bile acids being key molecular components regulating the gut microbiome composition during amphibian development and metamorphosis. Further studies into the metabolic interactions between amphibian tadpoles and their microbiota during early development and metamorphosis should provide useful information on the evolution of host-microbiota interactions in vertebrates.


Author(s):  
Indranil Chattopadhyay ◽  
Esaki M. Shankar

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.


Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 376 ◽  
Author(s):  
Tobias Hegelmaier ◽  
Marco Lebbing ◽  
Alexander Duscha ◽  
Laura Tomaske ◽  
Lars Tönges ◽  
...  

The impact of the gut microbiome is being increasingly appreciated in health and in various chronic diseases, among them neurodegenerative disorders such as Parkinson’s disease (PD). In the pathogenesis of PD, the role of the gut has been previously established. In conjunction with a better understanding of the intestinal microbiome, a link to the misfolding and spread of alpha-synuclein via inflammatory processes within the gut is discussed. In a case-control study, we assessed the gut microbiome of 54 PD patients and 32 healthy controls (HC). Additionally, we tested in this proof-of-concept study whether dietary intervention alone or additional physical colon cleaning may lead to changes of the gut microbiome in PD. 16 PD patients underwent a well-controlled balanced, ovo-lacto vegetarian diet intervention including short fatty acids for 14 days. 10 of those patients received additional treatment with daily fecal enema over 8 days. Stool samples were collected before and after 14 days of intervention. In comparison to HC, we could confirm previously reported PD associated microbiome changes. The UDPRS III significantly improved and the levodopa-equivalent daily dose decreased after vegetarian diet and fecal enema in a one-year follow-up. Additionally, we observed a significant association between the gut microbiome diversity and the UPDRS III and the abundance of Ruminococcaceae. Additionally, the abundance of Clostridiaceae was significantly reduced after enema. Dietary intervention and bowel cleansing may provide an additional non-pharmacologic therapeutic option for PD patients.


2016 ◽  
Vol 242 (2) ◽  
pp. 127-139 ◽  
Author(s):  
Javier Cabrera-Perez ◽  
Vladimir P Badovinac ◽  
Thomas S Griffith

Sepsis is a poorly understood syndrome of systemic inflammation responsible for hundreds of thousands of deaths every year. The integrity of the gut epithelium and competence of adaptive immune responses are notoriously compromised during sepsis, and the prevalent assumption in the scientific and medical community is that intestinal commensals have a detrimental role in the systemic inflammation and susceptibility to nosocomial infections seen in critically ill, septic patients. However, breakthroughs in the last decade provide strong credence to the idea that our mucosal microbiome plays an essential role in adaptive immunity, where a human host and its prokaryotic colonists seem to exist in a carefully negotiated armistice with compromises and benefits that go both ways. In this review, we re-examine the notion that intestinal contents are the driving force of critical illness. An overview of the interaction between the microbiome and the immune system is provided, with a special focus on the impact of commensals in priming and the careful balance between normal intestinal flora and pathogenic organisms residing in the gut microbiome. Based on the data in hand, we hypothesize that sepsis induces imbalances in microbial populations residing in the gut, along with compromises in epithelial integrity. As a result, normal antigen sampling becomes impaired, and proliferative cues are intermixed with inhibitory signals. This situates the microbiome, the gut, and its complex immune network of cells and bacteria, at the center of aberrant immune responses during and after sepsis.


Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 57 ◽  
Author(s):  
Ulrich Desselberger

The mammalian gut is colonized by a large variety of microbes, collectively termed ‘the microbiome’. The gut microbiome undergoes rapid changes during the first few years of life and is highly variable in adulthood depending on various factors. With the gut being the largest organ of immune responses, the composition of the microbiome of the gut has been found to be correlated with qualitative and quantitative differences of mucosal and systemic immune responses. Animal models have been very useful to unravel the relationship between gut microbiome and immune responses and for the understanding of variations of immune responses to vaccination in different childhood populations. However, the molecular mechanisms underlying optimal immune responses to infection or vaccination are not fully understood. The gut virome and gut bacteria can interact, with bacteria facilitating viral infectivity by different mechanisms. Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Łukasz Zadka ◽  
Karolina Chrabaszcz ◽  
Igor Buzalewicz ◽  
Ewelina Wiercigroch ◽  
Natalia Glatzel-Plucińska ◽  
...  

AbstractThe impact of the post-mortem interval (PMI) on the optical molecular characteristics of the colonic mucosa and the gut-associated lymphoid tissue (GALT) were examined by multi-parametric measurements techniques. Inflammatory cells were identified by immunohistochemical staining. Molecular parameters were estimated using the Raman spectroscopy (RS) and Fourier Transform Infrared (FTIR) spectroscopic imaging. The 3D refractive index (3D-RI) distributions of samples were determined using the digital holographic tomography. The distribution of immune cells between post-mortem (PM) and normal controls did show significant differences for CD4 (P = 0.0016) or CD8 (P < 0.0001), whose expression level was decreased in PM cases. No association was found between individual PMI values and inflammatory cell distribution. However, there was a tendency for a negative correlation between CD4+ cells and PMI (r = − 0.542, P = 0.032). The alterations ongoing in post-mortem tissue may suggest that PMI has a suppressive effect on the effector properties of the cell-mediated immunity. Moreover, it was confirmed that spectroscopic and digital holotomographic histology are also a useful technique for characterization of the differences in inflammation of varying intensity and in GALT imaging in a solid tissue. Anatomical location of immune cells and methods of tissue fixation determine the molecular and optical parameters of the examined cases.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Eiko Hayase ◽  
Robert R. Jenq

AbstractImmune checkpoint inhibitors (ICIs) are monoclonal antibodies that block immune inhibitory pathways. Administration of ICIs augments T cell-mediated immune responses against tumor, resulting in improved overall survival in cancer patients. It has emerged that the intestinal microbiome can modulate responses to ICIs via the host immune system and that the use of antibiotics can lead to reduced efficacy of ICIs. Recently, reports that fecal microbiota transplantation can lead to ICI therapy responses in patients previously refractory to therapy suggest that targeting the microbiome may be a viable strategy to reprogram the tumor microenvironment and augment ICI therapy. Intestinal microbial metabolites may also be linked to response rates to ICIs. In addition to response rates, certain toxicities that can arise during ICI therapy have also been found to be associated with the intestinal microbiome, including in particular colitis. A key mechanistic question is how certain microbes can enhance anti-tumor responses or, alternatively, predispose to ICI-associated colitis. Evidence has emerged that the intestinal microbiome can modulate outcomes to ICI therapies via two major mechanisms, including those that are antigen-specific and those that are antigen-independent. Antigen-specific mechanisms occur when epitopes are shared between microbial and tumor antigens that could enhance, or, alternatively, reduce anti-tumor immune responses via cross-reactive adaptive immune cells. Antigen-independent mechanisms include modulation of responses to ICIs by engaging innate and/or adaptive immune cells. To establish microbiome-based biomarkers of outcomes and specifically modulate the intestinal microbiome to enhance efficacy of ICIs in cancer immunotherapy, further prospective interventional studies will be required.


Bioimpacts ◽  
2021 ◽  
Author(s):  
Ata Mahmoodpoor ◽  
Ali Shamekh ◽  
Sarvin Sanaie

The impact of gut as the origin of different disorders has led to the "gut-origin concept" of diseases. The gut microbiome regulates host defenses against viral infections, thus dysbiosis can play a major role in triggering the cascade of inflammation and causing immune imbalances in COVID-19 patients. It appears that gut microbial signature in COVID-19 patients can be used as a potential diagnostic, therapeutic, and even a prognostic marker. Personalized nutrition therapy can be used by profiling the gut microbiota of individual patients and specialized probiotics/synbiotics to modify gut dysbiosis. Hence, improving overall immune responses can be recommended in these patients.


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