scholarly journals The Microbiome as a Therapeutic Target for Multiple Sclerosis: Can Genetically Engineered Probiotics Treat the Disease?

Diseases ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 33
Author(s):  
Hannah M. Kohl ◽  
Andrea R. Castillo ◽  
Javier Ochoa-Repáraz
Keyword(s):  
Multiple Sclerosis ◽  
Intestinal Microbiota ◽  
Genetically Engineered ◽  
Brain Inflammation ◽  
Protective Effects ◽  
Neuroinflammatory Disease ◽  
Initial Work ◽  
And Function ◽  
Work Done ◽  
The Impact

There is an increasing interest in the intestinal microbiota as a critical regulator of the development and function of the immune, nervous, and endocrine systems. Experimental work in animal models has provided the foundation for clinical studies to investigate associations between microbiota composition and function and human disease, including multiple sclerosis (MS). Initial work done using an animal model of brain inflammation, experimental autoimmune encephalomyelitis (EAE), suggests the existence of a microbiota–gut–brain axis connection in the context of MS, and microbiome sequence analyses reveal increases and decreases of microbial taxa in MS intestines. In this review, we discuss the impact of the intestinal microbiota on the immune system and the role of the microbiome–gut–brain axis in the neuroinflammatory disease MS. We also discuss experimental evidence supporting the hypothesis that modulating the intestinal microbiota through genetically modified probiotics may provide immunomodulatory and protective effects as a novel therapeutic approach to treat this devastating disease.

scholarly journals Deficiency of Prebiotic Fiber and Insufficient Signaling Through Gut Metabolite-Sensing Receptors Leads to Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 141 (17) ◽  
pp. 1393-1403 ◽  
Author(s):  
David M. Kaye ◽  
Waled A. Shihata ◽  
Hamdi A. Jama ◽  
Kirill Tsyganov ◽  
Mark Ziemann ◽  
...  
Keyword(s):  
Cardiovascular Health ◽  
T Regulatory Cells ◽  
Short Chain Fatty Acids ◽  
Cardiovascular Death ◽  
Protective Effects ◽  
Mild Hypertensive ◽  
And Function ◽  
Cardiac Manifestations ◽  
Prebiotic Fiber ◽  
The Impact

Background: High blood pressure (BP) continues to be a major, poorly controlled but modifiable risk factor for cardiovascular death. Among key Western lifestyle factors, a diet poor in fiber is associated with prevalence of high BP. The impact of lack of prebiotic fiber and the associated mechanisms that lead to higher BP are unknown. Here we show that lack of prebiotic dietary fiber leads to the development of a hypertensinogenic gut microbiota, hypertension and its complications, and demonstrate a role for G-protein coupled-receptors (GPCRs) that sense gut metabolites. Methods: One hundred seventy-nine mice including C57BL/6J, gnotobiotic C57BL/6J, and knockout strains for GPR41, GPR43, GPR109A, and GPR43/109A were included. C57BL/6J mice were implanted with minipumps containing saline or a slow-pressor dose of angiotensin II (0.25 mg·kg -1 ·d -1 ). Mice were fed diets lacking prebiotic fiber with or without addition of gut metabolites called short-chain fatty acids ([SCFA)] produced during fermentation of prebiotic fiber in the large intestine), or high prebiotic fiber diets. Cardiac histology and function, BP, sodium and potassium excretion, gut microbiome, flow cytometry, catecholamines and methylation-wide changes were determined. Results: Lack of prebiotic fiber predisposed mice to hypertension in the presence of a mild hypertensive stimulus, with resultant pathological cardiac remodeling. Transfer of a hypertensinogenic microbiota to gnotobiotic mice recapitulated the prebiotic-deprived hypertensive phenotype, including cardiac manifestations. Reintroduction of SCFAs to fiber-depleted mice had protective effects on the development of hypertension, cardiac hypertrophy, and fibrosis. The cardioprotective effect of SCFAs were mediated via the cognate SCFA receptors GPR43/GPR109A, and modulated L-3,4-dihydroxyphenylalanine levels and the abundance of T regulatory cells regulated by DNA methylation. Conclusions: The detrimental effects of low fiber Westernized diets may underlie hypertension, through deficient SCFA production and GPR43/109A signaling. Maintaining a healthy, SCFA-producing microbiota is important for cardiovascular health.

scholarly journals Intestinal microbiota during early life – impact on health and disease

2014 ◽  
Vol 73 (4) ◽  
pp. 457-469 ◽  
Author(s):  
Lotta Nylund ◽  
Reetta Satokari ◽  
Seppo Salminen ◽  
Willem M. de Vos
Keyword(s):  
Intestinal Microbiota ◽  
Early Life ◽  
Later Life ◽  
Related Factors ◽  
Life Impact ◽  
Health And Disease ◽  
And Function ◽  
The Impact

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.

scholarly journals Diverse Mechanisms Underlie Enhancement of Enteric Viruses by the Mammalian Intestinal Microbiota

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 760 ◽  
Author(s):  
Alexa N. Roth ◽  
Katrina R. Grau ◽  
Stephanie M. Karst
Keyword(s):  
Intestinal Microbiota ◽  
Pathogenic Bacteria ◽  
Enteric Viruses ◽  
Enteric Virus ◽  
Commensal Bacteria ◽  
Virus Infections ◽  
Virus Binding ◽  
Host Immune Responses ◽  
And Function ◽  
The Impact

Over the past two decades, there has been tremendous progress in understanding the impact of the intestinal microbiota on mammalian metabolism, physiology, and immune development and function. There has also been substantial advancement in elucidating the interplay between commensal and pathogenic bacteria. Relatively more recently, researchers have begun to investigate the effect of the intestinal microbiota on viral pathogenesis. Indeed, a growing body of literature has reported that commensal bacteria within the mammalian intestinal tract enhance enteric virus infections through a variety of mechanisms. Commensal bacteria or bacterial glycans can increase the stability of enteric viruses, enhance virus binding to host receptors, modulate host immune responses in a proviral manner, expand the numbers of host cell targets, and facilitate viral recombination. In this review, we will summarize the current literature exploring these effects of the intestinal microbiota on enteric virus infections.

scholarly journals Alterations in Intestinal Microbiota Composition in Mice Treated With Vitamin D3 or Cathelicidin

2021 ◽  
Vol 11 ◽  
Author(s):  
Yu Jiang ◽  
Yue Wan ◽  
Jing Li ◽  
Yueshui Zhao ◽  
Yongshun Ma ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Antimicrobial Peptide ◽  
Intestinal Microbiota ◽  
Vitamin D3 ◽  
Metabolic Pathways ◽  
Antimicrobial Activities ◽  
Protective Effects ◽  
Rrna Sequencing ◽  
The Impact ◽  
Harmful Effects

Gut microbiota is a complex aggregation of microbial organisms, which offers diverse protective benefits to the host. Dysbiosis of intestinal microbiota is frequently associated with many diseases. Vitamin D3 (VD), which was originally associated with bone health, also possesses antimicrobial activities and can act through antimicrobial peptide. Cathelicidin is a type of antimicrobial peptide in host to maintain the balance of gut microbiome. Our current study sought to evaluate the protective effect of VD and cathelicidin in mice intestines by administration of VD or mCRAMP-encoding L. lactis. We herein provided a comprehensive profile of the impact of VD and mCRAMP on gut microbiota using 16S rRNA sequencing, followed by bioinformatics and statistical analysis. Our results revealed an increased richness of bacterial community in mice intestines due to VD administration. Moreover, we showed a beneficial effect of VD and mCRAMP by enhancing the colonization of bacterial taxa that are associated with protective effects to the host but repressing the propagation of bacterial taxa that are associated with harmful effects to the host. Various metabolic pathways related to amino acid and lipid metabolism were affected in this process. We further established a bacterial panel as a reliable biomarker to evaluate the efficacy of remodeling the mice gut microbiota by VD and mCRAMP administration. The uncovered effects will deepen the comprehension about the antibacterial mechanisms of VD and mCRAMP and provide new insights for therapeutic implication of them.

scholarly journals Influência da Disbiose na Patologia do Couro Cabeludo

2021 ◽  
Vol 79 (4) ◽  
pp. 309-314
Author(s):  
Francisca Morgado ◽  
Rui Oliveira Soares
Keyword(s):  
Multiple Sclerosis ◽  
Ulcerative Colitis ◽  
Intestinal Microbiota ◽  
Alopecia Areata ◽  
Current Knowledge ◽  
Seborrheic Dermatitis ◽  
Immune Mediated ◽  
Few Data ◽  
Scalp Diseases ◽  
The Impact

In recent years, several studies have demonstrated the involvement of the intestinal microbiota in immune-mediated diseases such as diabetes, ulcerative colitis, and multiple sclerosis. There are few data on the follicular microbiome and its role in the pathogenesis of scalp diseases. Some studies show influence of dysbiosis on these diseases, and manipulation of the microbiome may represent a possible therapeu- tic option. This article reviews current knowledge regarding the impact of dysbiosis on dermatological diseases of the scalp, such as seborrheic dermatitis, psoriasis, alopecia areata, androgenetic alopecia, lichen planus pilaris, frontal fibrosing alopecia and decalvant folliculitis. A broader understanding of this may suggest additional treatments beyond conventional therapies.

scholarly journals Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier

2017 ◽  
Author(s):  
Lesley Hoyles ◽  
Tom Snelling ◽  
Umm-Kulthum Umlai ◽  
Jeremy K. Nicholson ◽  
Simon R. Carding ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Protective Effects ◽  
Microbial Metabolites ◽  
Blood Brain ◽  
Microbial Infections ◽  
Pathway Regulation ◽  
And Function ◽  
The Impact

AbstractBackgroundGut microbiota composition and function are symbiotically linked with host health, and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognized mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesized interactions between circulating gut–derived microbial metabolites and the blood–brain barrier (BBB) also contribute to the gut–brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed.ResultsAfter demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signaling.ConclusionsTogether, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut–brain axis that warrants further attention.

scholarly journals Development and Function of the Intestinal Microbiome and Potential Implications for Pig Production

Animals ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 76 ◽  
Author(s):  
Tanya Nowland ◽  
Kate Plush ◽  
Mary Barton ◽  
Roy Kirkwood
Keyword(s):  
Intestinal Microbiota ◽  
Management Practices ◽  
System Development ◽  
Critical Time ◽  
Intestinal Microbiome ◽  
Lactation Period ◽  
Time Period ◽  
Immune System Development ◽  
And Function ◽  
The Impact

The intestinal microbiota has received a lot of attention in recent times due to its essential role in the immune system development and function. Recent work in humans has demonstrated that the first year of life is the most critical time period for microbiome development with perturbations during this time being proven to have long term health consequences. In this review, we describe the literature surrounding early life events in humans and mice that contribute to intestinal microbiota development and function, and compare this to piglets predominantly during their lactation period, which focuses on the impact lactation management practices may have on the intestinal microbiota. Although extensive research has been conducted in this area in humans and mice, little research exists in pigs during perceivably the most critical time period of development, which is the lactation period. The research reviewed outlines the importance of appropriate intestinal microbiota development. However, further research is needed in order to understand the full extent routine farm practices have on a piglet’s intestinal microbiota.

Surgery for Lung Cancer and the Consequences for the Swallow

2016 ◽  
Vol 1 (13) ◽  
pp. 162-168
Author(s):  
Pippa Hales ◽  
Corinne Mossey-Gaston
Keyword(s):  
Lung Cancer ◽  
Treatment Options ◽  
Vocal Cord Palsy ◽  
Subsequent Treatment ◽  
Physiological Reserve ◽  
Palliative Phase ◽  
And Function ◽  
The Impact ◽  
Swallow Function

Lung cancer is one of the most commonly diagnosed cancers across Northern America and Europe. Treatment options offered are dependent on the type of cancer, the location of the tumor, the staging, and the overall health of the person. When surgery for lung cancer is offered, difficulty swallowing is a potential complication that can have several influencing factors. Surgical interaction with the recurrent laryngeal nerve (RLN) can lead to unilateral vocal cord palsy, altering swallow function and safety. Understanding whether the RLN has been preserved, damaged, or sacrificed is integral to understanding the effect on the swallow and the subsequent treatment options available. There is also the risk of post-surgical reduction of physiological reserve, which can reduce the strength and function of the swallow in addition to any surgery specific complications. As lung cancer has a limited prognosis, the clinician must also factor in the palliative phase, as this can further increase the burden of an already compromised swallow. By understanding the surgery and the implications this may have for the swallow, there is the potential to reduce the impact of post-surgical complications and so improve quality of life (QOL) for people with lung cancer.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

Investigating Burnt Mounds in Clydesdale during Motorway Construction

1998 ◽  
Vol 21 (1) ◽  
pp. 1-28
Author(s):  
John A Atkinson ◽  
Camilla Dickson ◽  
Jane Downes ◽  
Paul Robins ◽  
David Sanderson
Keyword(s):  
Bronze Age ◽  
Research Strategy ◽  
Archaeological Evidence ◽  
Radiocarbon Dates ◽  
Short Account ◽  
And Function ◽  
The Impact ◽  
The Bronze Age

Summary Two small burnt mounds were excavated as part of the programme to mitigate the impact of motorway construction in the Crawford area. The excavations followed a research strategy designed to address questions of date and function. This paper surveys the various competing theories about burnt mounds and how the archaeological evidence was evaluated against those theories. Both sites produced radiocarbon dates from the Bronze Age and evidence to suggest that they were cooking places. In addition, a short account is presented of two further burnt mounds discovered during the construction of the motorway in Annandale.

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