Socioeconomic drivers of the human microbiome footprint in global sewage

The human microbiome leaves a legacy in sewage ecosystems,also referred to as the human sewage microbiomes(HSM),and could cause potential risk to human health and ecosystem service.However,these host-associated communities remain understudied,especially at a global scale,regarding microbial diversity,community composition and the underlying drivers.Here,we built a metagenomic read mapping-based framework to estimate HSM abundance in 243 sewage samples from 60 countries across seven continents.Our approach revealed that 95.03%of human microbiome species were identified from global sewage,demonstrating the potential of sewage as a lens to explore these human-associated microbes while bypassing the limitations of human privacy concerns.We identified significant biogeographic patterns for the HSM community,with species richness increasing toward high latitudes and composition showing a distance-decay relationship at a global scale.Interestingly,the HSM communities were mainly clustered by continent,with those from Europe and North America being separated from Asia and Africa.Furthermore,global HSM diversity was shown to be shaped by both climate and socioeconomic variables.Specifically,the average annual temperature was identified as the most important factor for species richness(33.18%),whereas economic variables such as country export in goods and services contributed the most to the variation in community composition(27.53%).Economic and other socioeconomic variables,such as education,were demonstrated to have direct effects on the HSM,as indicated by structural equation modeling.Our study provides the global biogeography of human sewage microbiomes and highlights the economy as an important socioeconomic factor driving host-associated community composition.

Magnetotactic bacteria from the human gut microbiome associated with orientation and navigation regions of the brain

Magnetotactic bacteria(MTB),ubiquitous in soil and fresh and saltwater sources have been identified in the microbiome of humans and many animals.MTB endogenously produce magnetic nanocrystals enabling them to orient and navigate along geomagnetic fields.Similar magnetite deposits have been found throughout the tissues of the human brain,including brain regions associated with orientation such as the cerebellum and hippocampus,the origins of which remain unknown.Speculation over the role and source of MTB in humans,as well as any association with the brain,remain unanswered.We performed a metagenomic analysis of the gut microbiome of 34 healthy females as well as grey matter volume analysis in magnetite-rich brain regions associated with orientation and navigation with the goal of identifying specific MTB that could be associated with brain structure in orientation and navigation regions.We identified seven MTB in the human gut microbiome:Magnetococcus marinus,Magnetospira sp.QH-2,Magnetospirillum magneticum,Magnetospirillum sp.ME-1,Magnetospirillum sp.XM-1,Magnetospirillum gryphiswaldense,and Desulfovibrio magneticus.Our preliminary results show significant negative associations between multiple MTB with bilateral flocculonodular lobes of the cerebellum and hippocampus(adjusted for total intracranial volume,uncorrected P<0.05).These findings indicate that MTB in the gut are associated with grey matter volume in magnetite-rich brain regions related to orientation and navigation.These preliminary findings support MTB as a potential biogenic source for brain magnetite in humans.Further studies will be necessary to validate and elucidate the relationship between these bacteria,magnetite concentrations,and brain function.

An overview of major metagenomic studies on human microbiomes in health and disease

Many microbes are important symbiotes of human. They form specific microbiota communities, participate in various kinds of biological processes of their host and thus deeply affect human health status. Metagenomic sequencing has been widely used in human microbiota study due to its capacity of studying all genetic materials in an environment as a whole without any extra need of isolation or cultivation of microorganisms. Many efforts have been made by researchers in this area trying to dig out interesting knowledge from various metagenome data. In this review, we go through some prominent studies in the metagenomic area. We summarize them into three categories, constructing taxonomy and gene reference, characterization of microbiome distribution patterns, and detection of microbiome alternations associated with specific human phenotypes or diseases. Some available data resources are also provided. This review can serve as an entrance to this exciting and rapidly developing field for researchers interested in human microbiomes.

Sample Collection,DNA Extraction,and Library Construction Protocols of the Human Microbiome Studies in the International Human Phenome Project

The human microbiome plays a crucial role in human health.In the past decade,advances in high-throughput sequencing technologies and analytical software have significantly improved our knowledge of the human microbiome.However,most studies concerning the human microbiome did not provide repeatable protocols to guide the sample collection,handling,and processing procedures,which impedes obtaining valid and timely microbial taxonomic and functional results.This protocol provides detailed operation methods of human microbial sample collection,DNA extraction,and library construction for both the amplicon sequencing-based measurements of the microbial samples from the human nasal cavity,oral cavity,and skin,as well as the shotgun metagenomic sequencing-based measurements of the human stool samples among adult par-ticipants.This study intends to develop practical procedure standards to improve the reproducibility of microbiota profiling of human samples.

Human microbiome brings new insights to traditional Chinese medicine

The human microbiome has become a new frontier of life sciences and plays a crucial role in determining individual and population health.Over thousands of years of medical practice,practitioners of traditional Chinese medicine(TCM)developed an understanding of the importance and activity of commensal microorganisms without access to modern technology.In this review,we examine the theoretical similarities between modern studies of the human microbiome and TCM,and propose feasible strategies to integrate the 2 fields.Advances in our understanding of the human microbiome will also help to modernize the practice of TCM,thereby providing a basis for bridging the gap between modern medicine and TCM.

Impact of host genetics on gut microbiome: Take-home lessons from human and mouse studies

The intestinal microbiome has emerged as an important component involved in various diseases.Therefore,the interest in understanding the factors shaping its composition is growing.The gut microbiome,often defined as a complex trait,contains diverse components and its properties are determined by a combination of external and internal effects.Although much effort has been invested so far,it is still difficult to evaluate the extent to which human genetics shape the composition of the gut microbiota.However,in mouse studies,where the environmental factors are better controlled,the effect of the genetic background was significant.The purpose of this paper is to provide a current assessment of the role of human host genetics in shaping the gut microbiome composition.Despite the inconsistency of the reported results,it can be estimated that the genetic factor affects a portion of the microbiome.However,this effect is currently lower than the initial estimates,and it is difficult to separate the genetic influence from the environmental effect.Additionally,despite the differences between the microbial composition of humans and mice,results from mouse models can strengthen our knowledge of host genetics underlying the human gut microbial variation.

Microbiome and pancreatic cancer: A comprehensive topic review of literature

To review microbiome alterations associated with pancreatic cancer, its potential utility in diagnostics, risk assessment, and influence on disease outcomes.METHODSA comprehensive literature review was conducted by all-inclusive topic review from PubMed, MEDLINE, and Web of Science. The last search was performed in October 2016.RESULTSDiverse microbiome alterations exist among several body sites including oral, gut, and pancreatic tissue, in patients with pancreatic cancer compared to healthy populations.CONCLUSIONPilot study successes in non-invasive screening strategies warrant further investigation for future translational application in early diagnostics and to learn modifiable risk factors relevant to disease prevention. Pre-clinical investigations exist in other tumor types that suggest microbiome manipulation provides opportunity to favorably transform cancer response to existing treatment protocols and improve survival.

Over 50,000 Metagenomically Assembled Draft Genomes for the Human Oral Microbiome Reveal New Taxa

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64%of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candidate phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Porphyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral samples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.

Microbiome therapeutics:exploring the present scenario and challenges

Human gut-microbiome explorations have enriched our understanding ofmicrobial colonization,maturation,and dysbiosis in health-and-disease subsets.The enormousmetabolic potential of gutmicrobes and their role in themaintenance of human health is emerging,with new avenues to use themas therapeutic agents to overcome human disorders.Microbiome therapeutics are aimed at engineering the gutmicrobiome using additive,subtractive,ormodulatory therapy with an application of native or engineeredmicrobes,antibiotics,bacteriophages,and bacteriocins.This approach could overcome the limitation of conventional therapeutics by providing personalized,harmonized,reliable,and sustainable treatment.Its huge economic potential has been shown in the global therapeuticsmarket.Despite the therapeutic and economical potential,microbiome therapeutics is still in the developing stage and is facing various technical and administrative issues that require research attention.This review aims to address the current knowledge and landscape ofmicrobiome therapeutics,provides an overview of existing health-and-disease applications,and discusses the potential future directions ofmicrobiomemodulations.

Gut microbial interactions based on network construction and bacterial pairwise cultivation

Association networks are widely applied for the prediction of bacterial interactions in studies of human gut microbiomes.However,the experimental validation of the predicted interactions is challenging due to the complexity of gut microbiomes and the limited number of cultivated bacteria.In this study,we addressed this challenge by integrating in vitro time series network(TSN)associations and cocultivation of TSN taxon pairs.Fecal samples were collected and used for cultivation and enrichment of gut microbiome on YCFA agar plates for 13 days.Enriched cells were harvested for DNA extraction and metagenomic sequencing.A total of 198 metagenome-assembled genomes(MAGs)were recovered.Temporal dynamics of bacteria growing on the YCFA agar were used to infer microbial association networks.To experimentally validate the interactions of taxon pairs in networks,we selected 24 and 19 bacterial strains from this study and from the previously established human gut microbial biobank,respectively,for pairwise co-cultures.The co-culture experiments revealed that most of the interactions between taxa in networks were identified as neutralism(51.67%),followed by commensalism(21.67%),amensalism(18.33%),competition(5%)and exploitation(3.33%).Genome-centric analysis further revealed that the commensal gut bacteria(helpers and beneficiaries)might interact with each other via the exchanges of amino acids with high biosynthetic costs,short-chain fatty acids,and/or vitamins.We also validated 12 beneficiaries by adding 16 additives into the basic YCFA medium and found that the growth of 66.7%of these strains was significantly promoted.This approach provides new insights into the gut microbiome complexity and microbial interactions in association networks.Our work highlights that the positive relationships in gut microbial communities tend to be overestimated,and that amino acids,short-chain fatty acids,and vitamins are contributed to the positive relationships.

Gut microbiota,inflammation and colorectal cancer

Although genes contribute to colorectal cancer,the gut microbiota are an important player.Accumulating evidence suggests that chronic infection and the ensuing inflammation contributes to tumor initiation and tumor progression.A variety of bacterial species and tumor-promoting virulence mechanisms have been investigated.Significant advances have been made in understanding the composition and functional capabilities of the gut microbiota and its roles in cancer.In the current review,we discuss the novel roles of microbiota in the progression of colon cancer.Although microbiota technically include organisms other than bacteria e.g.,viruses and fungi,this review will primarily focus on bacteria.We summarize epidemiological studies of human microbiome and colon cancer.We discuss the progress in the scientific understanding of the interplay between the gut microbiota,barrier function,and host responses in experimental models.Further,we discuss the potential application in prevention,diagnosis,and therapy of colon cancer by targeting microbiota.We discuss the challenges lie ahead and the future direction in studying gut microbiome in colon cancer to close the gap between the basic sciences and clinical application.