Species-Level Profiling of <i>Ixodes pacificus</i> Bacterial Microbiomes Reveals High Variability Across Short Spatial Scales at Different Taxonomic Resolutions

Socarras, Kayla M.; Earl, Joshua P.; Król, Jarosław; Bhat, Archana; Pabilonia, Max; Harrison, Meghan H.; Lang, Steven P.; Sen, Bhaswati; Ahmed, Azad; Hester, Michael; Vandegrift, Kurt J.; Ehrlich, Garth D.

doi:10.1089/gtmb.2021.0088

Cited by 7 publications

(11 citation statements)

References 63 publications

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“…Diverse methods are available for rDNA amplification, all based on conserved sequences. Ehrlich and other researchers have devised a pandomain assay for specifically amplifying and sequencing rDNAs (16S for prokaryotes; and 18S/28S for eukaryotic microbes) and have demonstrated that the strategy is broadly inclusive, highly sensitive, and species‐specific 53,142,149,150 . The general method for 16S pandomain analyses reported by Earl et al 142 .…”

Section: Priority Issues To Be Addressedmentioning

confidence: 99%

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease

Lathe

Schultek²,

Balin

et al. 2023

Alzheimer's & Dementia

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Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

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Section: Priority Issues To Be Addressedmentioning

confidence: 99%

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease

Lathe

Schultek²,

Balin

et al. 2023

Alzheimer's & Dementia

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View full text Add to dashboard Cite

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“…Diverse methods are available for rDNA amplification, all based on conserved sequences. Ehrlich and colleagues have devised a pandomain assay for specifically amplifying and sequencing rDNAs (16S for prokaryotes; and 18S/23S for eukaryotic microbes) and have demonstrated that the strategy is broadly inclusive, highly sensitive, and species-specific [53,114,124,125]. The general method for 16S pandomain analyses reported by Earl et al was able to accurately characterize highly complex polymicrobial specimens containing hundreds of different species present at molar input levels that vary by more than three orders of magnitude.…”

Section: (Iii) Dna-based Rdna Amplificationmentioning

confidence: 99%

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration

Lathe

Schultek*²,

Balin

et al. 2023

Preprint

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Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post-mortem brain versus cerebrospinal fluid (CSF), blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, PCR and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

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“…Full-length 16S rRNA gene amplification. The taxonomic composition of bacterial communities in the post-mortem human brain tissues were analyzed using the Pacific Biosciences (PacBio) single molecule real-time (SMRT) sequencing technology (Pacific Biosciences, Menlo Park, CA, USA) to obtain the full-length 16S ribosomal RNA (rRNA) gene sequences as previously described [59,60,66]. Briefly, the full-length 16S rRNA gene was amplified using the universal 16S rRNA bacterial primers 27 F (5′-GRAGAGTTTGATYMTGGCTCA) and 1492 R (5′-TACGGYTACCTTGTTACGACTT).…”

Section: Biological Materials and Sequencingmentioning

confidence: 99%

“…In this study, we take advantage of the Pacific Biosciences (PacBio) long-read DNA sequencing technology we previously developed [59,60,66] to sequence the full-length bacterial 16S rRNA gene and to profile the bacterial communities to the species level in AD-affected and non-demented age-matched brains.…”

Section: Introductionmentioning

confidence: 99%

“…The vast majority of such microbial survey studies in AD have relied on molecular diagnostics in which the bacterial DNA is directly detected, either by a PCR-based methods [44,46] or in situ hybridization (FISH) [38] as opposed to cultural methods owing to the demonstrated difficulty in culturing bacteria associated with chronic infections and biofilms [47][48][49][50][51][52] and the greatly improved sensitivity and specificity of nucleic acid-based methods [53][54][55]. Most recently, species-specific, pan-domain molecular diagnostics have become available for bacteria [56][57][58][59][60]. These assays provide for unbiased surveys without the need for investigators to a priori decide what taxa to survey.…”

Section: Introductionmentioning

confidence: 99%

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Evidence for the Existence of a Bacterial Etiology for Alzheimer’s Disease and for a Temporal-Spatial Development of a Pathogenic Microbiome in the Brain

Moné

Earl

Król

et al. 2022

Preprint

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Background: Over the last few decades, a growing body of evidence suggests a role for various infectious agents in Alzheimers Disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, or fungi) being detected in AD subjects brains, most research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subject' brains. Results: We obtained post-mortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control aged-matched subjects with a total of 130 samples from the frontal and temporal lobes and entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify the bacteria. We detected bacteria in the brains of both cohorts with the principal bacteria comprising Propionibacterium acnes (recently renamed Cutibacterium acnes) and two species each of Acinetobacter and Comamonas genera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances we also employed an unconventional analysis approach that utilized Latent Dirichlet Allocation, often used in computational linguistics. This allowed us to identify 5 classes of samples, each revealing a different microbiome. Assuming that samples represented infections that potentially began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non- existence of AD. Conclusions: The AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance of Propionibacterium acnes with pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included: Methylobacterium, Bacillus, Caulobacter, Delftia, and Variovorax. P. acnes may also be involved with outcompeting the Comamonas species, which were strongly associated with non-demented brain microbiome, whose early destruction could be the first stage of the disease. The statistical results are also consistent with a leaky blood brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.

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Species-Level Profiling of Ixodes pacificus Bacterial Microbiomes Reveals High Variability Across Short Spatial Scales at Different Taxonomic Resolutions

Cited by 7 publications

References 63 publications

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease

Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease: Research outline and call for collaboration

Evidence for the Existence of a Bacterial Etiology for Alzheimer’s Disease and for a Temporal-Spatial Development of a Pathogenic Microbiome in the Brain

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