Baseline human gut microbiota profile in healthy people and standard reporting template

Abstract

A comprehensive knowledge of the types and ratios of microbes that inhabit the healthy human gut is necessary before any kind of pre-clinical or clinical study can be performed that attempts to alter the microbiome to treat a condition or improve therapy outcome. To address this need we present an innovative scalable comprehensive analysis workflow, a healthy human reference microbiome list and abundance profile (GutFeelingKB), and a novel Fecal Biome Population Report (FecalBiome) with clinical applicability. GutFeelingKB provides a list of 157 organisms (8 phyla, 18 classes, 23 orders, 38 families, 59 genera and 109 species) that forms the baseline biome and therefore can be used as healthy controls for studies related to dysbiosis. The incorporation of microbiome science into routine clinical practice necessitates a standard report for comparison of an individual’s microbiome to the growing knowledgebase of “normal” microbiome data. The FecalBiome and the underlying technology of GutFeelingKB address this need. The knowledgebase can be useful to regulatory agencies for the assessment of fecal transplant and other microbiome products, as it contains a list of organisms from healthy individuals. In addition to the list of organisms and abundances the study also generated a list of contigs of metagenomics dark matter. In this study, metagenomic dark matter represents sequences that cannot be mapped to any known sequence but can be assembled into contigs of 10,000 nucleotides or higher. These sequences can be used to create primers to study potential novel organisms. All data is freely available from https://hive.biochemistry.gwu.edu/gfkb and NCBI’s Short Read Archive.

Assessing and removing the effect of unwanted technical variations in microbiome data

“…Our study does not aim to replicate and validate the findings of such studies, but to show how, if left unaddressed, the differences in sample storage conditions could introduce significant changes in microbial abundance of abundant taxa which are potentially important for our understanding of particular conditions or diseases. The three most-affected bacterial classes in our study, namely Bacteroidia, Clostridia and Bacilli, are among the most dominant microbial classes in the mammalian gut [28][29][30] , therefore it is not surprising to see them strongly affected by technical variations. Both Bacteroidia and Clostridia classes in particular have been found to be significantly impacted by different storage methods in both metagenomic and metaproteomic data 27 .…”

Association between sphingomyelin levels and gut microbiota abundance: a two-sample Mendelian randomization study

“…In individuals with AD, the count of Ruminococcus callidus is lower. These ndings imply that Ruminococcus callidus could play a protective role in the development and progression of AD through the "gut microbiota abundance-gut-brain" connection [41][42][43] . Recent research has suggested a possible connection between speci c types of Streptococcus, such as Streptococcus pyogenes and Streptococcus suis, and the development of Alzheimer's disease.…”

Host Transcriptome and Microbiota Signatures Prior to Immunization Profile Vaccine Humoral Responsiveness

“…In stool, we found that Eubacterium abundance at baseline was positively correlated with the MVA-Nab response. This family of bacteria is known to be associated with gut health (51)(52)(53), and several of its species are higher in centenarians than in either young or elderly adults (54). The potential impact of the gut microbiota on vaccine immunogenicity has been already investigated with systemic vaccines (55) and with oral vaccines including those of rotavirus (RVV), polio, and cholera, mainly in infants/children living in lowincome countries (56,57).…”