Predictability and persistence of prebiotic dietary supplementation in a healthy human cohort

AbstractDietary interventions to manipulate the human gut microbiome for improved health have received increasing attention. However, their design has been limited by a lack of understanding of the quantitative impact of diet on a host’s microbiota. We present a highly controlled diet perturbation experiment in a healthy, human cohort in which individual micronutrients are spiked in against a standardized background. We identify strong and predictable responses of specific microbes across participants consuming prebiotic spike-ins, at the level of both strains and functional genes, suggesting fine-scale resource partitioning in the human gut. No predictable responses to non-prebiotic micronutrients were found. Surprisingly, we did not observe decreases in day-to-day variability of the microbiota compared to a complex, varying diet, and instead found evidence of diet-induced stress and an associated loss of biodiversity. Our data offer insights into the effect of a low complexity diet on the gut microbiome, and suggest that effective personalized dietary interventions will rely on functional, strain-level characterization of a patient’s microbiota.

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Systematic characterization of human gut microbiome-secreted molecules by integrated multi-omics

ISME Communications ◽

10.1038/s43705-021-00078-0 ◽

2021 ◽

Vol 1 (1) ◽

Author(s):

Bianca De Saedeleer ◽

Antoine Malabirade ◽

Javier Ramiro-Garcia ◽

Janine Habier ◽

Jean-Pierre Trezzi ◽

...

Keyword(s):

Gut Microbiome ◽

Complex Mixture ◽

Host Cells ◽

Methodological Framework ◽

Secretion Systems ◽

Human Gut ◽

Healthy Human ◽

Human Gut Microbiome ◽

Health And Disease

AbstractThe human gut microbiome produces a complex mixture of biomolecules that interact with human physiology and play essential roles in health and disease. Crosstalk between micro-organisms and host cells is enabled by different direct contacts, but also by the export of molecules through secretion systems and extracellular vesicles. The resulting molecular network, comprised of various biomolecular moieties, has so far eluded systematic study. Here we present a methodological framework, optimized for the extraction of the microbiome-derived, extracellular biomolecular complement, including nucleic acids, (poly)peptides, and metabolites, from flash-frozen stool samples of healthy human individuals. Our method allows simultaneous isolation of individual biomolecular fractions from the same original stool sample, followed by specialized omic analyses. The resulting multi-omics data enable coherent data integration for the systematic characterization of this molecular complex. Our results demonstrate the distinctiveness of the different extracellular biomolecular fractions, both in terms of their taxonomic and functional composition. This highlights the challenge of inferring the extracellular biomolecular complement of the gut microbiome based on single-omic data. The developed methodological framework provides the foundation for systematically investigating mechanistic links between microbiome-secreted molecules, including those that are typically vesicle-associated, and their impact on host physiology in health and disease.

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Enterotype Variations of the Healthy Human Gut Microbiome in Different Geographical Regions

Bioinformation ◽

10.6026/97320630014560 ◽

2018 ◽

Vol 14 (9) ◽

pp. 560-573 ◽

Cited By ~ 7

Author(s):

Fauzul Mobeen ◽

◽

Vikas Sharma ◽

Tulika Prakash ◽

◽

...

Keyword(s):

Gut Microbiome ◽

Human Gut ◽

Healthy Human ◽

Human Gut Microbiome ◽

Geographical Regions

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Defining a Healthy Human Gut Microbiome: Current Concepts, Future Directions, and Clinical Applications

Cell Host & Microbe ◽

10.1016/j.chom.2012.10.012 ◽

2012 ◽

Vol 12 (5) ◽

pp. 611-622 ◽

Cited By ~ 330

Author(s):

Fredrik Bäckhed ◽

Claire M. Fraser ◽

Yehuda Ringel ◽

Mary Ellen Sanders ◽

R. Balfour Sartor ◽

...

Keyword(s):

Gut Microbiome ◽

Clinical Applications ◽

Human Gut ◽

Healthy Human ◽

Future Directions ◽

Human Gut Microbiome

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Fire in the Forest: Adverse Effects of Antibiotics on the Healthy Human Gut Microbiome

International Journal of Medical Reviews ◽

10.29252/ijmr-050104 ◽

2018 ◽

Vol 5 (1) ◽

pp. 19-26

Author(s):

Manosha Perera ◽

Irosha Perera

Keyword(s):

Adverse Effects ◽

Gut Microbiome ◽

Human Gut ◽

Healthy Human ◽

Human Gut Microbiome

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Stable Engraftment of a Human Gut Bacterial Microbiome in Double Humanized BLT-mice

10.1101/749093 ◽

2019 ◽

Cited By ~ 1

Author(s):

Lance Daharsh ◽

Amanda E. Ramer-Tait ◽

Qingsheng Li

Keyword(s):

Immune System ◽

Gut Microbiome ◽

Human Disease ◽

Humanized Mice ◽

Rrna Gene ◽

Human Immune System ◽

Human Gut ◽

Healthy Human ◽

Human Immune

AbstractBackgroundHumanized mice featuring a functional human immune system are an important pre-clinical model for examining immune responses to human-specific pathogens. This model has been widely utilized to study human diseases that are otherwise impossible or difficult to investigate in humans or with other animal models. However, one limitation of using humanized mice is their native murine gut microbiome, which significantly differs from the one found in humans. These differences may be even greater for mice housed and bred in specific pathogen free conditions. Given the importance of the gut microbiome to human health and disease, these differences may profoundly impact the ability to translate the results from humanized mice studies to human disease. Further, there is a critical need for improved pre-clinical models to study the complex in vivo relationships of the gut microbiome, immune system, and human disease. We therefore created double humanized mice with both a functional human immune system and stable human-like gut microbiome.ResultsSurgery was performed on NOD.Cg-PrkdcscidII2rgtm1Wjl/SzJ (NSG) mice to create bone-marrow, liver, thymus (BLT) humanized mice. After immune reconstitution, mice were treated with broad spectrum antibiotics to deplete murine gut bacteria and then transplanted with fecal material from healthy human donors. Characterization of 173 fecal samples obtained from 45 humanized mice revealed that double humanized mice had unique 16S rRNA gene profiles consistent with those of the individual human donor samples. Importantly, transplanted human-like gut microbiomes were stable in mice for the duration of the study, up to 14.5 weeks post-transplant. Microbiomes of double humanized mice also harbored predicted functional capacities that more closely resembled those of the human donors compared to humanized mice.ConclusionsHere, we describe successful engraftment of a stable human microbiome in BLT humanized mice to further improve this preclinical humanized mouse model. These double humanized mice represent a unique and tractable new model to study the complex relationships between the human gut microbiome, human immune system, and human disease in vivo.

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Characterization of the SOS meta-regulon in the human gut microbiome

Bioinformatics ◽

10.1093/bioinformatics/btt753 ◽

2014 ◽

Vol 30 (9) ◽

pp. 1193-1197 ◽

Cited By ~ 5

Author(s):

Joseph P. Cornish ◽

Neus Sanchez-Alberola ◽

Patrick K. O’Neill ◽

Ronald O'Keefe ◽

Jameel Gheba ◽

...

Keyword(s):

Gut Microbiome ◽

Human Gut ◽

Human Gut Microbiome

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Reconstruction of ancient microbial genomes from the human gut

Nature ◽

10.1038/s41586-021-03532-0 ◽

2021 ◽

Author(s):

Marsha C. Wibowo ◽

Zhen Yang ◽

Maxime Borry ◽

Alexander Hübner ◽

Kun D. Huang ◽

...

Keyword(s):

Gut Microbiome ◽

Large Scale ◽

De Novo ◽

Human Gut ◽

Microbial Genomes ◽

Functional Profiling ◽

History Of ◽

Southwestern Usa ◽

Gut Microorganisms

AbstractLoss of gut microbial diversity1–6 in industrial populations is associated with chronic diseases7, underscoring the importance of studying our ancestral gut microbiome. However, relatively little is known about the composition of pre-industrial gut microbiomes. Here we performed a large-scale de novo assembly of microbial genomes from palaeofaeces. From eight authenticated human palaeofaeces samples (1,000–2,000 years old) with well-preserved DNA from southwestern USA and Mexico, we reconstructed 498 medium- and high-quality microbial genomes. Among the 181 genomes with the strongest evidence of being ancient and of human gut origin, 39% represent previously undescribed species-level genome bins. Tip dating suggests an approximate diversification timeline for the key human symbiont Methanobrevibacter smithii. In comparison to 789 present-day human gut microbiome samples from eight countries, the palaeofaeces samples are more similar to non-industrialized than industrialized human gut microbiomes. Functional profiling of the palaeofaeces samples reveals a markedly lower abundance of antibiotic-resistance and mucin-degrading genes, as well as enrichment of mobile genetic elements relative to industrial gut microbiomes. This study facilitates the discovery and characterization of previously undescribed gut microorganisms from ancient microbiomes and the investigation of the evolutionary history of the human gut microbiota through genome reconstruction from palaeofaeces.

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Metaproteomics as a tool for studying the protein landscape of human-gut bacterial species

10.1101/2021.09.02.458484 ◽

2021 ◽

Author(s):

Moses Stamboulian ◽

Jamie Canderan ◽

Yuzhen Ye

Keyword(s):

Human Health ◽

Gut Microbiome ◽

De Novo ◽

Bacterial Species ◽

Individual Species ◽

Human Gut ◽

Human Gut Microbiome ◽

Microbial Species ◽

Microbial Organisms

AbstractHost-microbiome interactions and the microbial community have broad impact in human health and diseases. Most microbiome based studies are performed at the genome level based on next-generation sequencing techniques, but metaproteomics is emerging as a powerful technique to study microbiome functional activity by characterizing the complex and dynamic composition of microbial proteins. We conducted a large-scale survey of human gut microbiome metaproteomic data to identify generalist species that are ubiquitously expressed across all samples and specialists that are highly expressed in a small subset of samples associated with a certain phenotype. We were able to utilize the metaproteomic mass spectrometry data to reveal the protein landscapes of these species, which enables the characterization of the expression levels of proteins of different functions and underlying regulatory mechanisms, such as operons. Finally, we were able to recover a large number of open reading frames (ORFs) with spectral support, which were missed by de novo protein-coding gene predictors. We showed that a majority of the rescued ORFs overlapped with de novo predicted proteincoding genes, but on opposite strands or on different frames. Together, these demonstrate applications of metaproteomics for the characterization of important gut bacterial species. Results are available for public access at https://omics.informatics.indiana.edu/GutBac.Author summaryMany reference genomes for studying human gut microbiome are available, but knowledge about how microbial organisms work is limited. Identification of proteins at individual species or community level provides direct insight into the functionality of microbial organisms. By analyzing more than a thousand metaproteomics datasets, we examined protein landscapes of more than two thousands of microbial species that may be important to human health and diseases. This work demonstrated new applications of metaproteomic datasets for studying individual genomes. We made the analysis results available through the GutBac website, which we believe will become a resource for studying microbial species important for human health and diseases.

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