Metagenomic estimation of absolute bacterial biomass in the mammalian gut through host-derived read normalization.

Absolute bacterial biomass estimation in the human gut is crucial for understanding microbiome dynamics and host-microbe interactions. Current methods for quantifying bacterial biomass in stool, such as flow cytometry, qPCR, or spike-ins (i.e.

Expanding the immune-related targetome of miR-155-5p by integrating time-resolved RNA patterns into miRNA target prediction.

The lack of a sufficient number of validated miRNA targets severely hampers the understanding of their biological function. Even for the well-studied miR-155-5p, there are only 239 experimentally validated targets out of 42,554 predicted targets. For a more complete assessment of the immune-related miR-155 targetome, we used an inverse correlation of time-resolved mRNA profiles and miR-155-5p expression of early CD4+ T cell activation to predict immune-related target genes.

Neonates exposed to HIV but uninfected exhibit an altered gut microbiota and inflammation associated with impaired breast milk antibody function.

Background: Infants exposed to HIV but uninfected have altered immune profiles which include heightened systemic inflammation. The mechanism(s) underlying this phenomenon is unknown. Here, we investigated differences in neonatal gut bacterial and viral microbiome and associations with inflammatory biomarkers in plasma.

Understanding disease-associated metabolic changes in human colon epithelial cells using ColonEpithelium metabolic reconstruction.

The colon epithelium plays a key role in the host-microbiome interactions, allowing uptake of various nutrients and driving important metabolic processes. To unravel detailed metabolic activities in the human colon epithelium, our present study focuses on the generation of the first cell-type specific genome-scale metabolic model (GEM) of human colonic epithelial cells, named iColonEpithelium. GEMs are powerful tools for exploring reactions and metabolites at systems level and predicting the flux distributions at steady state.

Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes.

The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin production of various C. difficile strains across different nutrient environments.

Aberrant bowel movement frequencies coincide with increased microbe-derived blood metabolites associated with reduced organ function.

Bowel movement frequency (BMF) directly impacts the gut microbiota and is linked to diseases like chronic kidney disease or dementia. In particular, prior work has shown that constipation is associated with an ecosystem-wide switch from fiber fermentation and short-chain fatty acid production to more detrimental protein fermentation and toxin production. Here, we analyze multi-omic data from generally healthy adults to see how BMF affects their molecular phenotypes, in a pre-disease context.

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner.

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known.

Microbial community-scale metabolic modelling predicts personalized short-chain fatty acid production profiles in the human gut.

Microbially derived short-chain fatty acids (SCFAs) in the human gut are tightly coupled to host metabolism, immune regulation and integrity of the intestinal epithelium. However, the production of SCFAs can vary widely between individuals consuming the same diet, with lower levels often associated with disease. A systems-scale mechanistic understanding of this heterogeneity is lacking.

Island biogeography theory provides a plausible explanation for why larger vertebrates and taller humans have more diverse gut microbiomes.

Prior work has shown a positive scaling relationship between vertebrate body size, human height, and gut microbiome alpha diversity. This observation mirrors commonly observed species area relationships (SARs) in many other ecosystems. Here, we expand these observations to several large datasets, showing that this size-diversity scaling relationship is independent of relevant covariates, like diet, body mass index, age, sex, bowel movement frequency, antibiotic usage, and cardiometabolic health markers.

Elucidating human gut microbiota interactions that robustly inhibit diverse strains across different nutrient landscapes.

The human gut pathogen displays extreme genetic variability and confronts a changeable nutrient landscape in the gut. We mapped gut microbiota inter-species interactions impacting the growth and toxin production of diverse strains in different nutrient environments. Although negative interactions impacting are prevalent in environments promoting resource competition, they are sparse in an environment containing -preferred carbohydrates.

Meta-analysis of the human upper respiratory tract microbiome reveals robust taxonomic associations with health and disease.

Background: The human upper respiratory tract (URT) microbiome, like the gut microbiome, varies across individuals and between health and disease states. However, study-to-study heterogeneity in reported case-control results has made the identification of consistent and generalizable URT-disease associations difficult.

Results: In order to address this issue, we assembled 26 independent 16S rRNA gene amplicon sequencing data sets from case-control URT studies, with approximately 2-3 studies per respiratory condition and ten distinct conditions covering common chronic and acute respiratory diseases.

Experimental capture of miRNA targetomes: disease-specific 3'UTR library-based miRNA targetomics for Parkinson's disease.

The identification of targetomes remains a challenge given the pleiotropic effect of miRNAs, the limited effects of miRNAs on individual targets, and the sheer number of estimated miRNA-target gene interactions (MTIs), which is around 44,571,700. Currently, targetome identification for single miRNAs relies on computational evidence and functional studies covering smaller numbers of targets. To ensure that the targetome analysis could be experimentally verified by functional assays, we employed a systematic approach and explored the targetomes of four miRNAs (miR-129-5p, miR-129-1-3p, miR-133b, and miR-873-5p) by analyzing 410 predicted target genes, both of which were previously associated with Parkinson's disease (PD).

Metagenomic estimation of dietary intake from human stool.

Dietary intake is tightly coupled to gut microbiota composition, human metabolism, and to the incidence of virtually all major chronic diseases. Dietary and nutrient intake are usually quantified using dietary questionnaires, which tend to focus on broad food categories, suffer from self-reporting biases, and require strong compliance from study participants. Here, we present MEDI (Metagenomic Estimation of Dietary Intake): a method for quantifying dietary intake using food-derived DNA in stool metagenomes.

The miRNA-target interactions: An underestimated intricacy.

MicroRNAs (miRNAs) play indispensable roles in posttranscriptional gene regulation. Their cellular regulatory impact is determined not solely by their sheer number, which likely amounts to >2000 individual miRNAs in human, than by the regulatory effectiveness of single miRNAs. Although, one begins to develop an understanding of the complex mechanisms underlying miRNA-target interactions (MTIs), the overall knowledge of MTI functionality is still rather patchy.

Disease-specific loss of microbial cross-feeding interactions in the human gut.

Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases.

Bifidobacterium infantis supplementation versus placebo in early life to improve immunity in infants exposed to HIV: a protocol for a randomized trial.

Introduction: Infants who are born from mothers with HIV (infants who are HIV exposed but uninfected; iHEU) are at higher risk of morbidity and display multiple immune alterations compared to infants who are HIV-unexposed (iHU). Easily implementable strategies to improve immunity of iHEU, and possibly subsequent clinical health outcomes, are needed. iHEU have altered gut microbiome composition and bifidobacterial depletion, and relative abundance of Bifidobacterium infantis has been associated with immune ontogeny, including humoral and cellular vaccine responses.

Growth phase estimation for abundant bacterial populations sampled longitudinally from human stool metagenomes.

Longitudinal sampling of the stool has yielded important insights into the ecological dynamics of the human gut microbiome. However, human stool samples are available approximately once per day, while commensal population doubling times are likely on the order of minutes-to-hours. Despite this mismatch in timescales, much of the prior work on human gut microbiome time series modeling has assumed that day-to-day fluctuations in taxon abundances are related to population growth or death rates, which is likely not the case.

Island biogeography theory and the gut: why taller people tend to harbor more diverse gut microbiomes.

Prior work has shown a positive scaling relationship between vertebrate body size and gut microbiome alpha-diversity. This observation mirrors commonly observed species area relationships (SAR) in many other ecosystems. Here, we show a similar scaling relationship between human height and gut microbiome alpha-diversity across two large, independent cohorts, controlling for a wide range of relevant covariates, such as body mass index, age, sex, and bowel movement frequency.

Coarse graining the human gut microbiome.

The composition of the human gut microbiome is heterogeneous across people. However, if you squint, co-abundant microbial genera emerge, accounting for much of this ecological variability. In this issue of Cell Host & Microbe, Frioux et al.

Personalized engraftment risk prediction and probiotic therapy assessment in the human gut.

colonizes up to 30-40% of community-dwelling adults without causing disease. infections (CDIs) are the leading cause of antibiotic-associated diarrhea in the U.S.

miR-34a-5p as molecular hub of pathomechanisms in Huntington's disease.

Background: Although a pivotal role of microRNA (miRNA, miR) in the pathogenesis of Huntington's disease (HD) is increasingly recognized, the molecular functions of miRNAs in the pathomechanisms of HD await further elucidation. One of the miRNAs that have been associated with HD is miR-34a-5p, which was deregulated in the mouse R6/2 model and in human HD brain tissues.

Methods: The aim of our study was to demonstrate interactions between miR-34a-5p and HD associated genes.

Generally-healthy individuals with aberrant bowel movement frequencies show enrichment for microbially-derived blood metabolites associated with reduced kidney function.

Bowel movement frequency (BMF) has been linked to changes in the composition of the human gut microbiome and to many chronic conditions, like metabolic disorders, neurodegenerative diseases, chronic kidney disease (CKD), and other intestinal pathologies like irritable bowel syndrome and inflammatory bowel disease. Lower BMF (constipation) can lead to compromised intestinal barrier integrity and a switch from saccharolytic to proteolytic fermentation within the microbiota, giving rise to microbially-derived toxins that may make their way into circulation and cause damage to organ systems. However, the connections between BMF, gut microbial metabolism, and the early-stage development and progression of chronic disease remain underexplored.

More is Different: Metabolic Modeling of Diverse Microbial Communities.

Microbial consortia drive essential processes, ranging from nitrogen fixation in soils to providing metabolic breakdown products to animal hosts. However, it is challenging to translate the composition of microbial consortia into their emergent functional capacities. Community-scale metabolic models hold the potential to simulate the outputs of complex microbial communities in a given environmental context, but there is currently no consensus for what the fitness function of an entire community should look like in the presence of ecological interactions and whether community-wide growth operates close to a maximum.

Multiomic signatures of body mass index identify heterogeneous health phenotypes and responses to a lifestyle intervention.

Multiomic profiling can reveal population heterogeneity for both health and disease states. Obesity drives a myriad of metabolic perturbations and is a risk factor for multiple chronic diseases. Here we report an atlas of cross-sectional and longitudinal changes in 1,111 blood analytes associated with variation in body mass index (BMI), as well as multiomic associations with host polygenic risk scores and gut microbiome composition, from a cohort of 1,277 individuals enrolled in a wellness program (Arivale).