The microbiome in health and disease: a new role of microbes in molecular medicine

Autenrieth, Ingo B.

doi:10.1007/s00109-016-1499-8

Cited by 16 publications

(9 citation statements)

References 15 publications

(15 reference statements)

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“…In this study, a number of choices had to be made regarding the design, analysis and interpretation of the metagenomic data. First, metagenomic sequencing allows the identification of viral and microbial genomes or genome 'traces', without however concluding presence of infectious pathogens [90][91][92] . Viral enrichment through gradient ultra-centrifugation can bias the sequencing output as it depends on previous knowledge of the physical properties of the virions or virus like particles 93,94 .…”

Section: Dysbiotic Structure Of the Asthmatic Viromementioning

confidence: 99%

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Megremis

Constantinides

Xepapadaki

et al. 2020

Preprint

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Asthma development and persistence is tightly linked to respiratory viruses. Viral presence is usually interrogated with targeted approaches during periods of disease activity and/or infections, thus neglecting viral occurrence during steady states. We investigate the virome in the upper respiratory system of healthy and asthmatic preschool children during asymptomatic/non-infection periods using metagenomics. Children with asthma have a characteristically dysbiotic virome that correlates to disease severity and control. The major component of dysbiosis is bacteriophage deficiency, while eukaryotic viral presence is increased. At the metacommunity level, differential virus species co-occurrence patterns suggest a decrease of the microbiota community resilience in asthma. Viral dysbiosis is therefore a key characteristic of asthma pathophysiology.

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Section: Dysbiotic Structure Of the Asthmatic Viromementioning

confidence: 99%

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Megremis

Constantinides

Xepapadaki

et al. 2020

Preprint

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“…The Henle–Koch postulates (that microbe X causes disease Y) represent another cornerstone of infection microbiology (Autenrieth, ; Evans, ; Gradmann, ; Segre, ); they require association of the proposed pathogen with the disease and non‐association in its absence, as well as reinfection leading to renewed disease. Specifically, ( i ) the microorganism must be found in diseased but not in healthy individuals; ( ii ) the microorganism must be cultured from the diseased individual; ( iii ) inoculation of a healthy individual with the cultured microorganism must recapitulate the disease; and finally ( iv ) the microorganism must be reisolated from the inoculated, diseased individual and must match the original microorganism.…”

Section: Step –1: a Dormant Blood And Tissue Microbiomementioning

confidence: 99%

“…Specifically, ( i ) the microorganism must be found in diseased but not in healthy individuals; ( ii ) the microorganism must be cultured from the diseased individual; ( iii ) inoculation of a healthy individual with the cultured microorganism must recapitulate the disease; and finally ( iv ) the microorganism must be reisolated from the inoculated, diseased individual and must match the original microorganism. Unfortunately these original concepts simply do not work in the case of dormant microbes (Antonelli & Cutler, ; Autenrieth, ; Byrd & Segre, ; Falkow, , ; Fredricks & Relman, ; Seal et al ., ), because it is not always possible to isolate culturable organisms from patients with the disease. In the case of Whipple's disease and the causative organism Tropheryma whipplei , a clear link between the disease and ultramicroscopically observable microbes was established (Maiwald & Relman, ; Relman et al ., ) long before sequencing methods (Bentley et al ., ) allowed the design of a medium in which the organism could be persuaded to replicate (Renesto et al ., ).…”

Section: Step –1: a Dormant Blood And Tissue Microbiomementioning

confidence: 99%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.

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“…Nevertheless, increasingly microbiome members are being associated with various chronic perturbations of health, leading to a broader application of the idea of microbiota modulation [57]. One approach to addressing issues of presence of undesired microorganisms is selective depletion of those organisms without otherwise modifying microbiomes [58], i.e., microbiome editing, which in principle can be addressed using phages [59]. As noted, phages similarly may be employed to selectively reduce numbers of specific, undesirable bacteria in foods.…”

Section: Discussionmentioning

confidence: 99%

Active bacteriophage biocontrol and therapy on sub-millimeter scales towards removal of unwanted bacteria from foods and microbiomes

Abedon

2017

AIMS Microbiology

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Bacteriophages can be used as antibacterial agents as a form of biological control, e.g., such as phage therapy. With active treatment, phages must “actively” produce new virions, in situ , to attain “inundative” densities, i.e., sufficient titers to eradicate bacteria over reasonable timeframes. Passive treatment, by contrast, can be accomplished using phages that are bactericidal but incapable of generating new phage virions in situ during their interaction with target bacteria. These ideas of active versus passive treatment come from theoretical considerations of phage therapy pharmacology, particularly as developed in terms of phage application to well-mixed cultures consisting of physically unassociated bacteria. Here I extend these concepts to bacteria which instead are physically associated. These are bacteria as found making up cellular arrangements or bacterial microcolonies—collectively, clonal bacterial “clumps”. I consider circumstances where active phage replication would be required to effect desired levels of bacterial clearance, but populations of bacteria nevertheless are insufficiently prevalent to support phage replication to bacteria-inundative densities across environments. Clumped bacteria, however, may still support active treatment at more local, i.e., sub-millimeter, within-clump spatial scales, and potential consequences of this are explored mathematically. Application is to the post-harvest biocontrol of foodborne pathogens, and potentially also to precise microbiome editing. Adequate infection performance by phages in terms of timely burst sizes, that is, other than just adsorption rates and bactericidal activity, thus could be important for treatment effectiveness even if bacterial densities overall are insufficient to support active treatment across environments. Poor phage replication during treatment of even low bacterial numbers, such as given food refrigeration during treatment, consequently could be problematic to biocontrol success. In practical terms, this means that the characterization of phages for such purposes should include their potential to generate new virions under realistic in situ conditions across a diversity of potential bacterial targets.

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The microbiome in health and disease: a new role of microbes in molecular medicine

Cited by 16 publications

References 15 publications

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

Bacteriophage deficiency characterizes respiratory virome dysbiosis in childhood asthma

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Active bacteriophage biocontrol and therapy on sub-millimeter scales towards removal of unwanted bacteria from foods and microbiomes

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