scholarly journals Synthetic Microbiomes on the Rise—Application in Deciphering the Role of Microbes in Host Health and Disease

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4173
Author(s):  
Silvia Bolsega ◽  
André Bleich ◽  
Marijana Basic

The intestinal microbiota conveys significant benefits to host physiology. Although multiple chronic disorders have been associated with alterations in the intestinal microbiota composition and function, it is still unclear whether these changes are a cause or a consequence. Hence, to translate microbiome research into clinical application, it is necessary to provide a proof of causality of host–microbiota interactions. This is hampered by the complexity of the gut microbiome and many confounding factors. The application of gnotobiotic animal models associated with synthetic communities allows us to address the cause–effect relationship between the host and intestinal microbiota by reducing the microbiome complexity on a manageable level. In recent years, diverse bacterial communities were assembled to analyze the role of microorganisms in infectious, inflammatory, and metabolic diseases. In this review, we outline their application and features. Furthermore, we discuss the differences between human-derived and model-specific communities. Lastly, we highlight the necessity of generating novel synthetic communities to unravel the microbial role associated with specific health outcomes and disease phenotypes. This understanding is essential for the development of novel non-invasive targeted therapeutic strategies to control and modulate intestinal microbiota in health and disease.

2014 ◽  
Vol 73 (4) ◽  
pp. 457-469 ◽  
Author(s):  
Lotta Nylund ◽  
Reetta Satokari ◽  
Seppo Salminen ◽  
Willem M. de Vos

In the first years after birth, the intestinal microbiota develops rapidly both in diversity and complexity while being relatively stable in healthy adults. Different life-style-related factors as well as medical practices have an influence on the early-life intestinal colonisation. We address the impact of some of these factors on the consecutive microbiota development and later health. An overview is presented of the microbial colonisation steps and the role of the host in that process. Moreover, new early biomarkers are discussed with examples that include the association of microbiota and atopic diseases, the correlation of colic and early development and the impact of the use of antibiotics in early life. Our understanding of the development and function of the intestinal microbiota is constantly improving but the long-term influence of early-life microbiota on later life health deserves careful clinical studies.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Guojun Wu ◽  
Naisi Zhao ◽  
Chenhong Zhang ◽  
Yan Y. Lam ◽  
Liping Zhao

AbstractTo demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem’s higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same “guild” if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of “guild” to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.


2021 ◽  
Vol 8 ◽  
Author(s):  
Emma E. Hamilton-Williams ◽  
Graciela L. Lorca ◽  
Jill M. Norris ◽  
Jessica L. Dunne

In recent years the role of the intestinal microbiota in health and disease has come to the forefront of medical research. Alterations in the intestinal microbiota and several of its features have been linked to numerous diseases, including type 1 diabetes (T1D). To date, studies in animal models of T1D, as well as studies in human subjects, have linked several intestinal microbiota alterations with T1D pathogenesis. Features that are most often linked with T1D pathogenesis include decreased microbial diversity, the relative abundance of specific strains of individual microbes, and altered metabolite production. Alterations in these features as well as others have provided insight into T1D pathogenesis and shed light on the potential mechanism by which the microbiota plays a role in T1D pathogenesis, yet the underlying factors leading to these alterations remains unknown. One potential mechanism for alteration of the microbiota is through diet and nutrition. Previous studies have shown associations of diet with islet autoimmunity, but a direct contributing factor has yet to be identified. Diet, through introduction of antigens and alteration of the composition and function of the microbiota, may elicit the immune system to produce autoreactive responses that result in the destruction of the beta cells. Here, we review the evidence associating diet induced changes in the intestinal microbiota and their contribution to T1D pathogenesis. We further provide a roadmap for determining the effect of diet and other modifiable factors on the entire microbiota ecosystem, including its impact on both immune and beta cell function, as it relates to T1D. A greater understanding of the complex interactions between the intestinal microbiota and several interacting systems in the body (immune, intestinal integrity and function, metabolism, beta cell function, etc.) may provide scientifically rational approaches to prevent development of T1D and other childhood immune and allergic diseases and biomarkers to evaluate the efficacy of interventions.


2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.


2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Catalán ◽  
Miguel Andrés Mansilla ◽  
Ashley Ferrier ◽  
Lilian Soto ◽  
Kristine Oleinika ◽  
...  

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.


2014 ◽  
Vol 995 ◽  
pp. 1-27 ◽  
Author(s):  
Mahbuba Rahman ◽  
M. Rubayet Hasan

Pentose phosphate (PP) pathway, which is ubiquitously present in all living organisms, is one of the major metabolic pathways associated with glucose metabolism. The most important functions of this pathway includes the generation of reducing equivalents in the form of NADPH for reductive biosynthesis, and production of ribose sugars for the biosynthesis of nucleotides, amino acids, and other macromolecules required by all living cells. Under normal conditions of growth, PP pathway is important for cell cycle progression, myelin formation, and the maintenance of the structure and function of brain, liver, cortex and other organs. Under diseased conditions, such as in cases of many metabolic, neurological or malignant diseases, pathological mechanisms augment due to defects in the PP pathway genes. Adoption of alternative metabolic pathways by cells that are metabolically abnormal, or malignant cells that are resistant to chemotherapeutic drugs often plays important roles in disease progression and severity. Accordingly, the PP pathway has been suggested to play critical roles in protecting cancer or abnormal cells by providing reduced environment, to protect cells from oxidative damage and generating structural components for nucleic acids biosynthesis. Novel drugs that targets one or more components of the PP pathway could potentially serve to overcome challenges associated with currently available therapeutic options for many metabolic and non-metabolic diseases. However, careful designing of drugs is critical that takes into the accounts of cell’s broader genomic, proteomic and metabolic contexts under consideration, in order to avoid undesirable side-effects. In this review, we discuss the role of PP pathway under normal and abnormal physiological conditions and the potential of the PP pathway as a target for new drug development to treat metabolic and non-metabolic diseases.


2018 ◽  
Vol 8 (9) ◽  
pp. 163 ◽  
Author(s):  
Caroline Gurvich ◽  
Kate Hoy ◽  
Natalie Thomas ◽  
Jayashri Kulkarni

Hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function have multiple effects on the development, maintenance and function of the brain. Sex differences in cognitive functioning have been reported in both health and disease, which may be partly attributed to sex hormones. The aim of the current paper was to provide a theoretical review of how sex hormones influence cognitive functioning across the lifespan as well as provide an overview of the literature on sex differences and the role of sex hormones in cognitive decline, specifically in relation to Alzheimer’s disease (AD). A summary of current hormone and sex-based interventions for enhancing cognitive functioning and/or reducing the risk of Alzheimer’s disease is also provided.


Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2621
Author(s):  
Yun Kyung Lee ◽  
Yu Seong Chung ◽  
Ji Hye Lee ◽  
Jin Mi Chun ◽  
Jun Hong Park

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.


Author(s):  
Christian M. Madsen ◽  
Anette Varbo ◽  
Børge G. Nordestgaard

The vast majority of research about HDL (high-density lipoprotein) has for decades revolved around the possible role of HDL in atherosclerosis and its therapeutic potential within cardiovascular disease prevention; however, failures with therapies aimed at increasing HDL cholesterol has left questions as to what the role and function of HDL in human health and disease is. Recent observational studies have further shown that extreme high HDL cholesterol is associated with high mortality leading to speculations that HDL could in some instances be harmful. In addition, evidence from observational, and to a lesser extent genetic, studies has emerged indicating that HDL might be associated with the development of other major noncardiovascular diseases, such as infectious disease, autoimmune disease, cancer, type 2 diabetes, kidney disease, and lung disease. In this review, we discuss (1) the association between extreme high HDL cholesterol and mortality and (2) the emerging human evidence linking HDL to several major diseases outside the realm of cardiovascular disease.


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