scholarly journals Host genetic associations with the gut microbiota in HIV-1-infected subjects: a pilot exploratory study

2018 ◽  
Author(s):  
Yolanda Guillén ◽  
Marc Noguera-Julian ◽  
Javier Rivera ◽  
Maria Casadellà ◽  
Muntsa Rocafort ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Methanogenic Archaea ◽  
Genetic Associations ◽  
Host Genetics ◽  
Genetic Landscape ◽  
Host Genetic ◽  
Gene Richness ◽  
The Impact ◽  
Hiv 1

AbstractThe impact of host genetics on gut microbial dynamics is debated. No study to date has investigated the possible role of host genetics in shaping the gut microbiota in HIV-1 infected subjects. With the aim of generating preliminary data to inform future host genetic studies, we performed an exploratory host exome analysis of 147 subjects either infected or at risk of becoming infected with HIV-1 from the MetaHIV cohort in Barcelona. Using a DNA microarray chip, we sought to identify host genetic variants associated to three specific microbial features with a potentially inheritable component, and which were previously found to be associated with gut dysbiosis in HIV infection, i.e.: gut enterotype, presence of methanogenic archaea and microbial gene richness. After correction for multiple comparisons, we did not observe any statistically significant association between the host’s genetic landscape and the explored gut microbiome traits. These findings will help design future, adequately-powered studies to assess the influence of host genetics in the microbiome of HIV-1-infected subjects.

scholarly journals Host genetic effects upon the early gut microbiota in a bovine model with graduated spectrum of genetic variation

2019 ◽  
Vol 14 (1) ◽  
pp. 302-317 ◽  
Author(s):  
Peixin Fan ◽  
Beilei Bian ◽  
Lin Teng ◽  
Corwin D. Nelson ◽  
J. Driver ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Gut Microbiota ◽  
Bos Taurus ◽  
Bos Indicus ◽  
Nucleotide Polymorphisms ◽  
Paternal Genome ◽  
Host Genetics ◽  
Microbe Interactions ◽  
Host Genetic

Abstract Multiple synergistic factors affect the development and composition of mammalian gut microbiota, but effects of host genetics remain unclear. To illuminate the role of host genetics on gut microbiota, we employed animals with a graduated spectrum of genetic variation with minimal environmental influences. We bred 228 calves with linearly varying breed composition from 100% Angus (Bos taurus) to 100% Brahman (Bos indicus), as a proxy for genetic variation, and then raised the offspring in the same environment with identical diets. We hypothesized each breed would harbor distinct gut microbiota due to genetic influence. We found that the gut microbiota of preweaning calves at 3 months old is significantly affected by host genetics, profoundly by paternal genome. We also demonstrate that single nucleotide polymorphisms in host mucin-encoding genes, critical for gut mucosal health, are significantly correlated with both breed composition and mucin-degrading gut bacteria. We further demonstrate host genetics indirectly changes gut microbiota composition via microbe–microbe interactions. These findings indicate a strong contribution by host genetics in shaping the gut microbiota during early life stages, shedding light on impact of animal breeding on gut microbiota, which is associated with animal growth and health.

scholarly journals Could the CCR5-Δ32 Mutation be Protective in SARS-CoV-2 Infection?

2021 ◽  
pp. S249-S252
Author(s):  
N STARČEVIĆ ČIZMAREVIĆ ◽  
M KAPOVIĆ ◽  
D RONČEVIĆ ◽  
S RISTIĆ
Keyword(s):  
Viral Infections ◽  
Allelic Frequency ◽  
European Population ◽  
Host Responses ◽  
Host Genetics ◽  
Ecologic Study ◽  
The Impact ◽  
Hiv 1 ◽  
Pandemic Wave

Increasing evidence points to host genetics as a factor in COVID-19 prevalence and outcome. CCR5 is a receptor for proinflammatory chemokines that are involved in host responses, especially to viruses. The CCR5-Δ32 minor allele is an interesting variant, given the role of CCR5 in some viral infections, particularly HIV-1. Recent studies of the impact of CCR5-Δ32 on COVID-19 risk and severity have yielded contradictory results. This ecologic study shows that the CCR5-Δ32 allelic frequency in a European population was significantly negatively correlated with the number of COVID-19 cases (p=0.035) and deaths (p=0.006) during the second pandemic wave. These results suggest that CCR5-Δ32 may be protective against SARS-CoV-2 infection, as it is against HIV infection, and could be predictive of COVID-19 risk and severity. Further studies based on samples from populations of different genetic backgrounds are needed to validate these statistically obtained findings.

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals Oral Iron Supplementation—Gastrointestinal Side Effects and the Impact on the Gut Microbiota

2021 ◽  
Vol 12 (2) ◽  
pp. 491-502
Author(s):  
Sarah R. Bloor ◽  
Rudolph Schutte ◽  
Anthony R. Hobson
Keyword(s):  
Side Effects ◽  
Gut Microbiota ◽  
Iron Supplementation ◽  
Methanogenic Archaea ◽  
Intravenous Iron ◽  
Oral Iron ◽  
Intestinal Lumen ◽  
Gastrointestinal Side Effects ◽  
Potential Link ◽  
The Impact

Iron deficiency anaemia (IDA) is a worldwide healthcare problem affecting approximately 25% of the global population. The most common IDA treatment is oral iron supplementation, which has been associated with gastrointestinal (GI) side effects such as constipation and bloating. These can result in treatment non-adherence and the persistence of IDA. Intravenous iron does not cause GI side effects, which may be due to the lack of exposure to the intestinal lumen. Luminal iron can cause changes to the gut microbiota, aiding the promotion of pathogenic species and decreasing beneficial protective species. Iron is vital for methanogenic archaea, which rely on iron for growth and metabolism. Increased intestinal methane has been associated with slowing of intestinal transit, constipation, and bloating. Here we explore the literature to understand a potential link between iron and methanogenesis as a novel way to understand the mechanism of oral iron supplementation induced GI side effects.

scholarly journals Phenotypic Susceptibility to Bevirimat in Isolates from HIV-1-Infected Patients without Prior Exposure to Bevirimat

2010 ◽  
Vol 54 (6) ◽  
pp. 2345-2353 ◽  
Author(s):  
Nicolas A. Margot ◽  
Craig S. Gibbs ◽  
Michael D. Miller
Keyword(s):  
Recombinant Viruses ◽  
Gag Polyprotein ◽  
New Class ◽  
Major Mutation ◽  
Hiv Drugs ◽  
The Impact ◽  
First Time ◽  
Hiv 1

ABSTRACT Bevirimat (BVM) is the first of a new class of anti-HIV drugs with a novel mode of action known as maturation inhibitors. BVM inhibits the last cleavage of the Gag polyprotein by HIV-1 protease, leading to the accumulation of the p25 capsid-small peptide 1 (SP1) intermediate and resulting in noninfectious HIV-1 virions. Early clinical studies of BVM showed that over 50% of the patients treated with BVM did not respond to treatment. We investigated the impact of prior antiretroviral (ARV) treatment and/or natural genetic diversity on BVM susceptibility by conducting in vitro phenotypic analyses of viruses made from patient samples. We generated 31 recombinant viruses containing the entire gag and protease genes from 31 plasma samples from HIV-1-infected patients with (n = 21) or without (n = 10) prior ARV experience. We found that 58% of the patient isolates tested had a >10-fold reduced susceptibility to BVM, regardless of the patient's ARV experience or the level of isolate resistance to protease inhibitors. Analysis of mutants with site-directed mutations confirmed the role of the V370A SP1 polymorphism (SP1-V7A) in resistance to BVM. Furthermore, we demonstrated for the first time that a capsid polymorphism, V362I (CA protein-V230I), is also a major mutation conferring resistance to BVM. In contrast, none of the previously defined resistance-conferring mutations in Gag selected in vitro (H358Y, L363M, L363F, A364V, A366V, or A366T) were found to occur among the viruses that we analyzed. Our results should be helpful in the design of diagnostics for prediction of the potential benefit of BVM treatment in HIV-1-infected patients.

scholarly journals The gut-microbiota-brain axis in autism: what Drosophila models can offer?

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Safa Salim ◽  
Ayesha Banu ◽  
Amira Alwa ◽  
Swetha B. M. Gowda ◽  
Farhan Mohammad
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Autism Spectrum ◽  
Brain Disorders ◽  
Mediated Communication ◽  
The Impact ◽  
Insight Into ◽  
Drosophila Models

AbstractThe idea that alterations in gut-microbiome-brain axis (GUMBA)-mediated communication play a crucial role in human brain disorders like autism remains a topic of intensive research in various labs. Gastrointestinal issues are a common comorbidity in patients with autism spectrum disorder (ASD). Although gut microbiome and microbial metabolites have been implicated in the etiology of ASD, the underlying molecular mechanism remains largely unknown. In this review, we have summarized recent findings in human and animal models highlighting the role of the gut-brain axis in ASD. We have discussed genetic and neurobehavioral characteristics of Drosophila as an animal model to study the role of GUMBA in ASD. The utility of Drosophila fruit flies as an amenable genetic tool, combined with axenic and gnotobiotic approaches, and availability of transgenic flies may reveal mechanistic insight into gut-microbiota-brain interactions and the impact of its alteration on behaviors relevant to neurological disorders like ASD.

Role of the gut microbiota in airway immunity and host defense against respiratory infections

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Maike Willers ◽  
Dorothee Viemann
Keyword(s):  
Gut Microbiota ◽  
Host Defense ◽  
Gut Microbiome ◽  
Respiratory Infections ◽  
Current Knowledge ◽  
Viral Pathogens ◽  
Commensal Microbiota ◽  
Enhanced Resistance ◽  
The Impact

Abstract Colonization of the intestine with commensal bacteria is known to play a major role in the maintenance of human health. An altered gut microbiome is associated with various ensuing diseases including respiratory diseases. Here, we summarize current knowledge on the impact of the gut microbiota on airway immunity with a focus on consequences for the host defense against respiratory infections. Specific gut commensal microbiota compositions and functions are depicted that mediate protection against respiratory infections with bacterial and viral pathogens. Lastly, we highlight factors that have imprinting effects on the establishment of the gut microbiota early in life and are potentially relevant in the context of respiratory infections. Deepening our understanding of these relationships will allow to exploit the knowledge on how gut microbiome maturation needs to be modulated to ensure lifelong enhanced resistance towards respiratory infections.

scholarly journals Influence of microbiota on immunity and immunotherapy for gastric and esophageal cancers

2020 ◽  
Vol 8 (3) ◽  
pp. 206-214
Author(s):  
Xiaoli Zhang ◽  
Zui Pan
Keyword(s):  
Gut Microbiota ◽  
Human Health ◽  
Potential Role ◽  
Systemic Immunity ◽  
Esophageal Cancers ◽  
The Impact

Abstract Gastric and esophageal cancers are multifactorial and multistage-involved malignancy. While the impact of gut microbiota on overall human health and diseases has been well documented, the influence of gastric and esophageal microbiota on gastric and esophageal cancers remains unclear. This review will discuss the reported alteration in the composition of gastric and esophageal microbiota in normal and disease conditions, and the potential role of dysbiosis in carcinogenesis and tumorigenesis. This review will also discuss how dysbiosis stimulates local and systemic immunity, which may impact on the immunotherapy for cancer.

scholarly journals Flow Cytometry Analysis of HIV-1 Env Conformations at the Surface of Infected Cells and Virions: Role of Nef, CD4, and SERINC5

2019 ◽  
Vol 94 (6) ◽  
Author(s):  
Isabelle Staropoli ◽  
Jérémy Dufloo ◽  
Anaïs Ducher ◽  
Pierre-Henri Commere ◽  
Anna Sartori-Rupp ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Cellular Proteins ◽  
Viral Infectivity ◽  
Viral Particles ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Env Protein ◽  
The Impact ◽  
Hiv 1

ABSTRACT The HIV-1 Env protein is exposed at the surface of virions and infected cells. Env fluctuates between different closed and open structural states and these conformations influence both viral infectivity and sensitivity to antibody binding and neutralization. We established a flow virometry assay to visualize Env proteins at the surface of human immunodeficiency virus type 1 (HIV-1) virions. The assay is performed on ultracentrifuged fluorescent viral particles that are stained with a panel of broadly neutralizing antibodies (bNAbs) and nonneutralizing antibodies (nnAbs) that probe different epitopes of Env. We used this assay to compare Env at the surface of producer cells and viral particles and to analyze the effect of Nef, CD4, and SERINC5 on Env accessibility to antibodies. We studied the laboratory-adapted strain NL4-3 and two transmitted/founder viruses, THRO and CH058. We confirm that antibody accessibility varies between viral strains and show that Nef, CD4, and SERINC5 additively impact Env conformations. We further demonstrate that the Env accessibility profile on virions is globally similar to that observed on HIV-1-infected cells, with some noticeable differences. For instance, nnAbs bind to virions more efficiently than to producer cells, likely reflecting changes in Env conformational states on mature viral particles. This test complements other techniques and provides a convenient and simple tool for quantifying and probing the structure of Env at the virion surface and to analyze the impact of viral and cellular proteins on these parameters. IMPORTANCE HIV-1 Env conformation is one of the key parameters determining viral infectivity. The flow virometry-based assay developed in this study allows for the characterization of proteins incorporated in HIV-1 particles. We studied the conformation of HIV-1 Env and the impact that the viral protein Nef and the cellular proteins CD4 and SERINC5 have on Env accessibility to antibodies. Our assay permitted us to highlight some noticeable differences in the conformation of Env between producer cells and viral particles. It contributes to a better understanding of the actual composition of HIV-1 particles.

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