scholarly journals Patterns of 'Analytical Irreproducibility' in Multimodal Diseases

2020 ◽  
Author(s):  
Abigail R Basson ◽  
Fabio Cominelli ◽  
Alexander Rodriguez-Palacios
Keyword(s):  
Animal Studies ◽  
Data Distribution ◽  
Human Microbiome ◽  
Kernel Density ◽  
Human Diseases ◽  
Human Gut ◽  
Disease Subtype ◽  
Visualization Of Data ◽  
Microbiome Data

Abstract Background: Multimodal diseases are those in which affected individuals can be divided into subtypes (or ‘data modes’); for instance, ‘mild’ vs. ‘severe’, based on (unknown) modifiers of disease severity exemplified in the majority of microbiome-mediated human diseases. Studies have shown that despite the inclusion of a large number of subjects, the causal role of the microbiome in human diseases remains uncertain. The role of the microbiome in multimodal diseases has been studied in animals; however, findings are often deemed irreproducible, or unreasonably biased, with pathogenic roles in 95% of reports. As a solution to repeatability, investigators have been recently recommended to seek funds to increase the number of human-microbiome donors (N) to increase the reproducibility of animal studies. Herein, we outline the constraints of such recommendation. Results: Using published (observed) mean±SD microbiome data from human gut microbiota (hGM)-associated rodent studies, we illustrate through a series of simulations, that increasing N will not uniformly/universally enable the identification of consistent statistical differences (patterns of analytical irreproducibility), due to random sampling from a population with ample variability in disease and the presence of ‘disease data subtypes’ (or modes). To visualize data distribution, we used kernel-density-violin plots (rarely used in rodent studies; 0%, 0/38, 95%CI=6.9e-18,9.1) as a method to identify ‘disease data subtypes’. We also found that hGM preclinical rodent studies do not use cluster statistics when needed (97.4%, 37/38, 95%CI=86.5,99.5), and that scientists who increased N, concurrently reduced the number of mice/donor ( y =-0.21 x, R 2 =0.24 ; and vice versa), indicating that statistically, scientists replace the disease variance in mice by the variance of human disease in their studies. Conclusion: Instead of assuming that increasing N will solve reproducibility and identify clinically-predictive findings on causality in preclinical microbiome studies, we propose the visualization of data distribution using kernel-density’-violin plots to identify ‘disease data subtypes’ to self-correct, guide and promote the personalized investigation of disease subtype mechanisms.

scholarly journals Patterns of ‘Analytical Irreproducibility’ in Multimodal Diseases

2020 ◽  
Author(s):  
Abigail R Basson ◽  
Fabio Cominelli ◽  
Alex Rodriguez-Palacios
Keyword(s):  
Disease Severity ◽  
Random Sampling ◽  
Animal Studies ◽  
Human Microbiome ◽  
Relevant Information ◽  
List Type ◽  
Disease Subtype ◽  
Visualization Of Data ◽  
Statistical Effects

AbstractMultimodal diseases are those in which affected individuals can be divided into subtypes (or ‘data modes’); for instance, ‘mild’ vs. ‘severe’, based on (unknown) modifiers of disease severity. Studies have shown that despite the inclusion of a large number of subjects, the causal role of the microbiome in human diseases remains uncertain. The role of the microbiome in multimodal diseases has been studied in animals; however, findings are often deemed irreproducible, or unreasonably biased, with pathogenic roles in 95% of reports. As a solution to repeatability, investigators have been told to seek funds to increase the number of human-microbiome donors (N) to increase the reproducibility of animal studies (doi:10.1016/j.cell.2019.12.025). Herein, through simulations, we illustrate that increasing N will not uniformly/universally enable the identification of consistent statistical differences (patterns of analytical irreproducibility), due to random sampling from a population with ample variability in disease and the presence of ‘disease data subtypes’ (or modes). We also found that studies do not use cluster statistics when needed (97.4%, 37/38, 95%CI=86.5,99.5), and that scientists who increased N, concurrently reduced the number of mice/donor (y=-0.21x, R2=0.24; and vice versa), indicating that statistically, scientists replace the disease variance in mice by the variance of human disease. Instead of assuming that increasing N will solve reproducibility and identify clinically-predictive findings on causality, we propose the visualization of data distribution using kernel-density-violin plots (rarely used in rodent studies; 0%, 0/38, 95%CI=6.9e-18,9.1) to identify ‘disease data subtypes’ to self-correct, guide and promote the personalized investigation of disease subtype mechanisms.HighlightsMultimodal diseases are those in which affected individuals can be divided into subtypes (or ‘data modes’); for instance, ‘mild’ vs. ‘severe’, based on (unknown) modifiers of disease severity.The role of the microbiome in multimodal diseases has been studied in animals; however, findings are often deemed irreproducible, or unreasonably biased, with pathogenic roles in 95% of reports.As a solution to repeatably, investigators have been told to seek funds to increase the number of human-microbiome donors (N) to increase the reproducibility of animal studies.Herein, we illustrate that although increasing N could help identify statistical effects (patterns of analytical irreproducibility), clinically-relevant information will not always be identified.Depending on which diseases need to be compared, ‘random sampling’ alone leads to reproducible ‘patterns of analytical irreproducibility’ in multimodal disease simulations.Instead of solely increasing N, we illustrate how disease multimodality could be understood, visualized and used to guide the study of diseases by selecting and focusing on ‘disease modes’.

scholarly journals Microbiome in Health: Establishment, Metabolism, Immunity and Neuronal Pathway

2020 ◽  
Vol 3 (2) ◽  
pp. 379-383
Author(s):  
Matthew Obaineh Ojezele ◽  
Simon Irikefe Ovuakporaye ◽  
Emmanuel Adesola Adedapo
Keyword(s):  
Human Body ◽  
Gut Microbiome ◽  
Lymphoid Tissue ◽  
Human Microbiome ◽  
Postnatal Period ◽  
Tissue Growth ◽  
Intestinal Immunity ◽  
Human Gut ◽  
Host Genotype

The studies on microbiome encountered a blast, lately, as scientists become mindful of the role of microbiota in the advancement of specifi c kinds of maladies. The human microbiome is described as a community of microorganisms of different taxa colonizing the human body; this includes the metagenomics and metabolomics of these organisms. Humans have customized microbiome in terms of distribution and composition which are partly determined by host genotype as well as the initial colonization which takes place after delivery. The human gut microbiome has a vital infl uence on immunity and how it responds to body signals, which is very important for the lymphoid tissue growth, maintenance, and regulation of intestinal immunity. This review aimed at providing an overview of the role of the human microbiome in health spanning the development of the microbiome in utero to postnatal period. 

scholarly journals Mycobiome in the Gut: A Multiperspective Review

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Voon Kin Chin ◽  
Voon Chen Yong ◽  
Pei Pei Chong ◽  
Syafinaz Amin Nordin ◽  
Rusliza Basir ◽  
...  
Keyword(s):  
Potential Role ◽  
Good Health ◽  
Research Area ◽  
Human Diseases ◽  
Fungal Metabolites ◽  
Multiple Perspectives ◽  
Human Gut ◽  
Sequencing Technologies ◽  
Actual Mechanism

Human gut is home to a diverse and complex microbial ecosystem encompassing bacteria, viruses, parasites, fungi, and other microorganisms that have an undisputable role in maintaining good health for the host. Studies on the interplay between microbiota in the gut and various human diseases remain the key focus among many researchers. Nevertheless, advances in sequencing technologies and computational biology have helped us to identify a diversity of fungal community that reside in the gut known as the mycobiome. Although studies on gut mycobiome are still in its infancy, numerous sources have reported its potential role in host homeostasis and disease development. Nonetheless, the actual mechanism of its involvement remains largely unknown and underexplored. Thus, in this review, we attempt to discuss the recent advances in gut mycobiome research from multiple perspectives. This includes understanding the composition of fungal communities in the gut and the involvement of gut mycobiome in host immunity and gut-brain axis. Further, we also discuss on multibiome interactions in the gut with emphasis on fungi-bacteria interaction and the influence of diet in shaping gut mycobiome composition. This review also highlights the relation between fungal metabolites and gut mycobiota in human homeostasis and the role of gut mycobiome in various human diseases. This multiperspective review on gut mycobiome could perhaps shed new light for future studies in the mycobiome research area.

GUT Microbiome-GUT Dysbiosis-Arterial Hypertension: New Horizons

2019 ◽  
Vol 15 (1) ◽  
pp. 40-46 ◽  
Author(s):  
Vasiliki Katsi ◽  
Matthaios Didagelos ◽  
Stamatios Skevofilax ◽  
Iakovos Armenis ◽  
Athanasios Kartalis ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Arterial Hypertension ◽  
Animal Studies ◽  
Human Microbiome ◽  
Bioactive Metabolites ◽  
Human Gut ◽  
Fecal Microbiome ◽  
New Horizons ◽  
Blood Pressure Homeostasis ◽  
Treatment Responsiveness

Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.

Experimental Amyloidosis Induced by Immune Complex

1971 ◽  
Vol 29 ◽  
pp. 582-583
Author(s):  
A. Kawaoi
Keyword(s):  
Immune Complex ◽  
Systemic Amyloidosis ◽  
Human Diseases ◽  
Experimental Amyloidosis ◽  
Freund’S Complete Adjuvant ◽  
Freund's Complete Adjuvant ◽  
Immunological Approach ◽  
Experimentally Induced

Numbers of immunological approach have been made to the amyloidosis through the variety of predisposing human diseases and the experimentally induced animals by the greater number of agents. The results suggest an important role of impaired immunity involving both humoral and cell-mediated aspects.Recently the author has succeeded in producing amyloidosis in the rabbits and mice by the injections of immune complex of heat denatured DNA.The aim of this report is to demonstrate the details of the ultrastructure of the amyloidosis induced by heterologous insoluble immune complex. Eleven of twelve mice, dd strain, subcutaneously injected twice a week with Freund's complete adjuvant and four of seven animals intraperitonially injected developed systemic amyloidosis two months later from the initial injections. The spleens were electron microscopically observed.

Gut Mycobiota and Fungal Metabolites in Human Homeostasis

2018 ◽  
Vol 20 (2) ◽  
pp. 232-240 ◽  
Author(s):  
Izabella Mogilnicka ◽  
Marcin Ufnal
Keyword(s):  
Wide Spectrum ◽  
Biological Effects ◽  
Fungal Species ◽  
Fungal Metabolites ◽  
Human Gut ◽  
Fecal Transplantation ◽  
Bacterial Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Background:Accumulating evidence suggests that microbiota play an important role in host’s homeostasis. Thus far, researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.Methods:We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.Results:Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.Conclusion:The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.

scholarly journals Hypoxia and Mitochondrial Dysfunction in Pregnancy Complications

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 405 ◽  
Author(s):  
Xiang-Qun Hu ◽  
Lubo Zhang
Keyword(s):  
Pregnancy Complications ◽  
Intrauterine Growth Restriction ◽  
Animal Studies ◽  
Major Effect ◽  
Causative Role ◽  
Therapeutic Approaches ◽  
Maternal Complications ◽  
Mitochondrial Ros ◽  
Subsequent Risk

Hypoxia is a common and severe stress to an organism’s homeostatic mechanisms, and hypoxia during gestation is associated with significantly increased incidence of maternal complications of preeclampsia, adversely impacting on the fetal development and subsequent risk for cardiovascular and metabolic disease. Human and animal studies have revealed a causative role of increased uterine vascular resistance and placental hypoxia in preeclampsia and fetal/intrauterine growth restriction (FGR/IUGR) associated with gestational hypoxia. Gestational hypoxia has a major effect on mitochondria of uteroplacental cells to overproduce reactive oxygen species (ROS), leading to oxidative stress. Excess mitochondrial ROS in turn cause uteroplacental dysfunction by damaging cellular macromolecules, which underlies the pathogenesis of preeclampsia and FGR. In this article, we review the current understanding of hypoxia-induced mitochondrial ROS and their role in placental dysfunction and the pathogenesis of pregnancy complications. In addition, therapeutic approaches selectively targeting mitochondrial ROS in the placental cells are discussed.

scholarly journals Influence of pig farming on human Gut Microbiota: role of airborne microbial communities

Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1-13
Author(s):  
Julia Moor ◽  
Tsering Wüthrich ◽  
Suzanne Aebi ◽  
Nadezda Mostacci ◽  
Gudrun Overesch ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Communities ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Pig Farming

scholarly journals Sex differences in the phylum‐level human gut microbiota composition

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Alexander Koliada ◽  
Vladislav Moseiko ◽  
Mariana Romanenko ◽  
Oleh Lushchak ◽  
Nadiia Kryzhanovska ◽  
...  
Keyword(s):  
Sex Differences ◽  
Gut Microbiota ◽  
Age Groups ◽  
Microbiota Composition ◽  
Human Gut ◽  
Cross Sectional ◽  
Total N ◽  
Human Gut Microbiota ◽  
Gut Microbiota Composition

Abstract Background Evidence was previously provided for sex-related differences in the human gut microbiota composition, and sex-specific discrepancy in hormonal profiles was proposed as a main determinant of these differences. On the basis of these findings, the assumption was made on the role of microbiota in the sexual dimorphism of human diseases. To date, sex differences in fecal microbiota were demonstrated primarily at lower taxonomic levels, whereas phylum-level differences between sexes were reported in few studies only. In the present population-based cross-sectional research, sex differences in the phylum-level human gut microbiota composition were identified in a large (total n = 2301) sample of relatively healthy individuals from Ukraine. Results Relative abundances of Firmicutes and Actinobacteria, as determined by qRT-PCR, were found to be significantly increased, while that of Bacteroidetes was significantly decreased in females compared to males. The Firmicutes to Bacteroidetes (F/B) ratio was significantly increased in females compared to males. Females had 31 % higher odds of having F/B ratio more than 1 than males. This trend was evident in all age groups. The difference between sexes was even more pronounced in the elder individuals (50+): in this age group, female participants had 56 % higher odds of having F/B ratio > 1 than the male ones. Conclusions In conclusion, sex-specific differences in the phylum-level intestinal microbiota composition were observed in the Ukraine population. The F/B ratio was significantly increased in females compared to males. Further investigation is needed to draw strong conclusions regarding the mechanistic basis for sex-specific differences in the gut microbiota composition and regarding the role of these differences in the initiation and progression of human chronic diseases.

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