Microbiome Gene Research Articles

Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children’s hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung–immune system–microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

Metagenomics profiling of the microbial community and functional differences in solid-state fermentation vinegar starter (seed Pei) from different Chinese regions.

The starter used in solid-state fermentation (SSF) vinegar, known as seed Pei is a microbial inoculant from the previous batch that is utilized during the acetic acid fermentation stage. The seed Pei, which has a notable impact on vinegar fermentation and flavor, is under-researched with comparative studies on microorganisms. Herein metagenomics was employed to reveal the microbes and their potential metabolic functions of four seed Pei from three regions in China. The predominant microbial taxa in all four starters were bacteria, followed by viruses, eukaryotes, and archaea, with Lactobacillus sp. or Acetobacter sp. as main functional taxa. The seed Pei used in Shanxi aged vinegar (SAV) and Sichuan bran vinegar (SBV) exhibited a higher similarity in microbial composition and distribution of functional genes, while those used in two Zhenjiang aromatic vinegar (ZAV) differed significantly. Redundancy analysis (RDA) of physicochemical factors and microbial communities indicated that moisture content, pH, and reducing sugar content are significant factors influencing microbial distribution. Moreover, seven metagenome-assembled genomes (MAGs) that could potentially represent novel species were identified. There are distinctions in the microbiome and functional genes among different seed Pei. The vinegar starters were rich in genes related to carbohydrate metabolism. This research provides a new perspective on formulating vinegar fermentation starters and developing commercial fermentation agents for vinegar production.

Role of Gut Microbe Composition in Psychosocial Symptom Response to Exercise Training in Breast Cancer Survivors (ROME) study: protocol for a randomised controlled trial

IntroductionBreast cancer survivors have an increased risk for chronic fatigue and altered gut microbiota composition, both with negative health and quality of life affects. Exercise modestly improves fatigue and is...

Assembly and succession of the phyllosphere microbiome and nutrient-cycling genes during plant community development in a glacier foreland

The phyllosphere, particularly the leaf surface of plants, harbors a diverse range of microbiomes that play a vital role in the functioning of terrestrial ecosystems. However, our understanding of microbial successions and their impact on functional genes during plant community development is limited. In this study, considering core and satellite microbial taxa, we characterized the phyllosphere microbiome and functional genes in various microhabitats (i.e., leaf litter, moss and plant leaves) across the succession of a plant community in a low-altitude glacier foreland. Our findings indicate that phyllosphere microbiomes and associated ecosystem stability increase during the succession of the plant community. The abundance of core taxa increased with plant community succession and was primarily governed by deterministic processes. In contrast, satellite taxa abundance decreased during plant community succession and was mainly governed by stochastic processes. The abundance of microbial functional genes (such as C, N, and P hydrolysis and fixation) in plant leaves generally increased during the plant community succession. However, in leaf litter and moss leaves, only a subset of functional genes (e.g., C fixation and degradation, and P mineralization) showed a tendency to increase with plant community succession. Ultimately, the community of both core and satellite taxa collaboratively influenced the characteristics of phyllosphere nutrient-cycling genes, leading to the diverse profiles and fluctuating abundance of various functional genes during plant community succession. These findings offer valuable insights into the phyllosphere microbiome and plant–microbe interactions during plant community development, advancing our understanding of the succession and functional significance of the phyllosphere microbial community.

Discrepant soil microbial community and C cycling function responses to conventional and biodegradable microplastics

Biodegradable microplastics (MPs) are promising alternatives to conventional MPs and are of high global concern. However, their discrepant effects on soil microorganisms and functions are poorly understood. In this study, polyethylene (PE) and polylactic acid (PLA) MPs were selected to investigate the different effects on soil microbiome and C-cycling genes using high-throughput sequencing and real-time quantitative PCR, as well as the morphology and functional group changes of MPs, using scanning electron microscopy and Fourier transform infrared spectroscopy, and the driving factors were identified. The results showed that distinct taxa with potential for MP degradation and nitrogen cycling were enriched in soils with PLA and PE, respectively. PLA, smaller size (150-180 μm), and 5% (w/w) of MPs enhanced the network complexity compared with PE, larger size (250-300 μm), and 1% (w/w) of MPs, respectively. PLA increased β-glucosidase by up to 2.53 times, while PE (150–180 μm) reduced by 38.26%–44.01% and PE (250–300 μm) increased by 19.00%–22.51% at 30 days. Amylase was increased by up to 5.83 times by PLA (150–180 μm) but reduced by 40.26%–62.96% by PLA (250–300 μm) and 16.11%–43.92% by PE. The genes cbbL, cbhI, abfA, and Lac were enhanced by 37.16%-1.99 times, 46.35%-26.46 times, 8.41%-69.04%, and 90.81%-5.85 times by PLA except for PLA1B/5B at 30 days. These effects were associated with soil pH, NO3-–N, and MP biodegradability. These findings systematically provide an understanding of the impact of biodegradable MPs on the potential for global climate change.

Biofilm enhances the interactive effects of microplastics and oxytetracycline on zebrafish intestine

The enhanced adsorption of pollutants on biofilm-developed microplastics has been proved in many studies, but the ecotoxicological effects of biofilm-developed microplastics on organisms are still unclear. In this study, adult zebrafish were exposed to original microplastics, biofilm-developed microplastics, original microplastics absorbed with oxytetracycline (OTC), and biofilm-developed microplastics absorbed with OTC for 30 days. The intestinal histological damage, intestinal biomarker response, gut microbiome and antibiotic resistance genes (ARGs) profile of zebrafish were measured to explore the roles of biofilm in the effects of microplastics. The results showed that biofilm-developed microplastics significantly increased the number of goblet cells in intestinal epithelium compared with the control group. The biofilm-developed microplastics also induced the oxidative response in the zebrafish intestines, and biofilm changed the response mode in the combined treatment with OTC. Additionally, the biofilm-developed microplastics caused intestinal microbiome dysbiosis, and induced the abundance of some pathogenic genera increasing by several times compared with the control group and the original microplastics treatments, regardless of OTC adsorption. Furthermore, the abundance of ARGs in biofilm-developed microplastics increased significantly compared with the control and the original microplastic treatments. This study emphasized the significant influence and unique role of biofilm in microplastic studies.

Adjudicative efficacy of Bifidobacterium animalis subsp. lactis BLa80 in treating acute diarrhea in children: a randomized, double-blinded, placebo-controlled study

The goal of this study is to assess the efficacy and safety of Bifidobacterium animalis subsp. lactis BLa80, as an adjunct treatment for diarrhea in children with a randomized, double-blinded, placebo-controlled study design. Eligible diarrheal children, aged 0–3 years without the need for antibiotic treatment based on clinical diagnosis when recruited, were randomized into the intervention group (IG, n = 58, with probiotic) or the control group (CG, n = 53, placebo). The primary assessment was the duration of diarrhea. Fecal samples were collected for biochemical index measurement, analysis of gut microbiome composition, and prediction of gene family abundances. The total duration of diarrhea in the IG (122.6 ± 13.1 h) was significantly shorter than in the CG (148.4 ± 17.6 h, p < 0.001). More children in the IG showed improvements in diarrhea compared to the CG, both in intention-to-treat analysis (81.7% vs. 40.0%, p < 0.001) and per protocol analysis (84.4% vs 45.3%, p < 0.001). Cathelicidin level in the IG was significantly higher than that in the CG after the intervention (4415.00 ± 1036.93 pg/g vs. 3679.49 ± 871.18 pg/g, p = 0.0175). The intervention led to an increased abundance of Bifidobacterium breve and Collinsella aerofaciens species, higher alpha-diversity (p < 0.05), and enrichment of functional genes in the gut microbiota related to immunity regulation. Administration of BLa80 at a dose of 5 × 109 CFU/day resulted in a shorter duration of diarrhea and alterations in gut microbiome composition and gene functions.

Metagenomics insights into microbiome and antibiotic resistance genes from free living amoeba in chlorinated wastewater effluents

Free living amoeba (FLA) are among the organisms commonly found in wastewater and are well-established hosts for diverse microbial communities. Despite its clinical significance, there is little knowledge on the FLA microbiome and resistome, with previous studies relying mostly on conventional approaches. In this study we comprehensively analyzed the microbiome, antibiotic resistome and virulence factors (VFs) within FLA isolated from final treated effluents of two wastewater treatment plants (WWTPs) using shotgun metagenomics. Acanthamoeba has been identified as the most common FLA, followed by Entamoeba. The bacterial diversity showed no significant difference (p > 0.05) in FLA microbiomes obtained from the two WWTPs. At phylum level, the most dominant taxa were Proteobacteria, followed by Firmicutes and Actinobacteria. The most abundant genera identified were Enterobacter followed by Citrobacter, Paenibacillus, and Cupriavidus. The latter three genera are reported here for the first time in Acanthamoeba. In total, we identified 43 types of ARG conferring resistance to cephalosporins, phenicol, streptomycin, trimethoprim, quinolones, cephalosporins, tigecycline, rifamycin, and kanamycin. Similarly, a variety of VFs in FLA metagenomes were detected which included flagellar proteins, Type IV pili twitching motility proteins (pilH and rpoN), alginate biosynthesis genes AlgI, AlgG, AlgD and AlgW and Type VI secretion system proteins and general secretion pathway proteins (tssM, tssA, tssL, tssK, tssJ, fha, tssG, tssF, tssC and tssB, gspC, gspE, gspD, gspF, gspG, gspH, gspI, gspJ, gspK, and gspM). To the best of our knowledge, this is the first study of its kind to examine both the microbiomes and resistome in FLA, as well as their potential pathogenicity in treated effluents. Additionally, this study showed that FLA can host a variety of potentially pathogenic bacteria including Paenibacillus, and Cupriavidus that had not previously been reported, indicating that their relationship may play a role in the spread and persistence of antibiotic resistant bacteria (ARBs) and antibiotic resistance genes (ARGs) as well as the evolution of novel pathogens.

Characterization of rumen microbiome and immune genes expression of crossbred beef steers with divergent residual feed intake phenotypes

We investigated whole blood and hepatic mRNA expressions of immune genes and rumen microbiome of crossbred beef steers with divergent residual feed intake phenotype to identify relevant biological processes underpinning feed efficiency in beef cattle. Low-RFI beef steers (n = 20; RFI = − 1.83 kg/d) and high-RFI beef steers (n = 20; RFI = + 2.12 kg/d) were identified from a group of 108 growing crossbred beef steers (average BW = 282 ± 30.4 kg) fed a high-forage total mixed ration after a 70-d performance testing period. At the end of the 70-d testing period, liver biopsies and blood samples were collected for total RNA extraction and cDNA synthesis. Rumen fluid samples were also collected for analysis of the rumen microbial community. The mRNA expression of 84 genes related to innate and adaptive immunity was analyzed using pathway-focused PCR-based arrays. Differentially expressed genes were determined using P-value ≤ 0.05 and fold change (FC) ≥ 1.5 (in whole blood) or ≥ 2.0 (in the liver). Gene ontology analysis of the differentially expressed genes revealed that pathways related to pattern recognition receptor activity, positive regulation of phagocytosis, positive regulation of vitamin metabolic process, vascular endothelial growth factor production, positive regulation of epithelial tube formation and T-helper cell differentiation were significantly enriched (FDR < 0.05) in low-RFI steers. In the rumen, the relative abundance of PeH15, Arthrobacter, Moryella, Weissella, and Muribaculaceae was enriched in low-RFI steers, while Methanobrevibacter, Bacteroidales_BS11_gut_group, Bacteroides and Clostridium_sensu_stricto_1 were reduced. In conclusion, our study found that low-RFI beef steers exhibit increased mRNA expression of genes related to immune cell functions in whole blood and liver tissues, specifically those involved in pathogen recognition and phagocytosis regulation. Additionally, these low-RFI steers showed differences in the relative abundance of some microbial taxa which may partially account for their improved feed efficiency compared to high-RFI steers.

Metagenomic exploration of Andaman region of the Indian Ocean

Ocean microbiome is crucial for global biogeochemical cycles and primary productivity. Despite numerous studies investigating the global ocean microbiomes, the microbiome composition of the Andaman region of the Indian Ocean remains largely unexplored. While this region harbors pristine biological diversity, the escalating anthropogenic activities along coastal habitats exert an influence on the microbial ecology and impact the aquatic ecosystems. We investigated the microbiome composition in the coastal waters of the Andaman Islands by 16S rRNA gene amplicon and metagenomic shotgun sequencing approaches and compared it with the Tara Oceans Consortium. In the coastal waters of the Andaman Islands, a significantly higher abundance and diversity of Synechococcus species was observed with a higher abundance of photosynthesis pigment-related genes to adapt to variable light conditions and nutrition. In contrast, Prochlorococcus species showed higher abundance in open ocean water samples of the Indian Ocean region, with a relatively limited functional diversity. A higher abundance of antibiotic-resistance genes was also noted in the coastal waters region. We also updated the ocean microbiome gene catalog with 93,172 unique genes from the Andaman coastal water microbiome. This study provides valuable insights into the Indian Ocean microbiome and supplements the global marine microbial ecosystem studies.

Insights into the Microbiome and Antibiotic Resistance Genes from Hospital Environmental Surfaces: A Prime Source of Antimicrobial Resistance.

Hospital environmental surfaces are potential reservoirs for transmitting hospital-associated pathogens. This study aimed to profile microbiomes and antibiotic resistance genes (ARGs) from hospital environmental surfaces using 16S rRNA amplicon and metagenomic sequencing at a tertiary teaching hospital in Malaysia. Samples were collected from patient sinks and healthcare staff counters at surgery and orthopaedic wards. The samples' DNA were subjected to 16S rRNA amplicon and shotgun sequencing to identify bacterial taxonomic profiles, antibiotic resistance genes, and virulence factor pathways. The bacterial richness was more diverse in the samples collected from patient sinks than those collected from staff counters. Proteobacteria and Verrucomicrobia dominated at the phylum level, while Bacillus, Staphylococcus, Pseudomonas, and Acinetobacter dominated at the genus level. Staphylococcus epidermidis and Staphylococcus aureus were prevalent on sinks while Bacillus cereus dominated the counter samples. The highest counts of ARGs to beta-lactam were detected, followed by ARGs against fosfomycin and cephalosporin. We report the detection of mcr-10.1 that confers resistance to colistin at a hospital setting in Malaysia. The virulence gene pathways that aid in antibiotic resistance gene transfer between bacteria were identified. Environmental surfaces serve as potential reservoirs for nosocomial infections and require mitigation strategies to control the spread of antibiotic resistance bacteria.

Short-duration selective decontamination of the digestive tract infection control does not contribute to increased antimicrobial resistance burden in a pilot cluster randomised trial (the ARCTIC Study)

ObjectiveSelective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention of enhanced infection control. Here, we aim to characterise the changes to the microbiome and...

Low-density polyethylene enhances the disturbance of microbiome and antibiotic resistance genes transfer in soil-earthworm system induced by pyraclostrobin

Non-antibiotic chemicals in farmlands, including microplastics (MPs) and pesticides, have the potential to influence the soil microbiome and the dissemination of antibiotic resistance genes (ARGs). Despite this, there is limited understanding of the combined effects of MPs and pesticides on microbial communities and ARGs transmission in soil ecosystems. In this study, we observed that low-density polyethylene (LDPE) microplastic enhance the accumulation of pyraclostrobin in earthworms, resulting in reduced weight and causing severe oxidative damage. Analysis of 16 S rRNA amplification revealed that exposure to pyraclostrobin and/or LDPE disrupts the microbial community structure at the phylum and genus levels, leading to reduced alpha diversity in both the soil and earthworm gut. Furthermore, co-exposure to LDPE and pyraclostrobin increased the relative abundance of ARGs in the soil and earthworm gut by 2.15 and 1.34 times, respectively, compared to exposure to pyraclostrobin alone. It correlated well with the increasing relative abundance of genera carrying ARGs. Our findings contribute novel insights into the impact of co-exposure to MPs and pesticides on soil and earthworm microbiomes, highlighting their role in promoting the transfer of ARGs. This knowledge is crucial for managing the risk associated with the dissemination of ARGs in soil ecosystems.

Effects of Fishmeal Substitution with Mealworm Meals (Tenebrio molitor and Alphitobius diaperinus) on the Growth, Physiobiochemical Response, Digesta Microbiome, and Immune Genes Expression of Atlantic Salmon (Salmo salar).

A 12-week growth trial was conducted to assess the effects of mealworm meals, as a substitution for fishmeal, on the growth, physiobiochemical responses, digesta microbiome, and immune-related genes expression of Atlantic salmon (Salmo salar). Twenty Atlantic salmon parr (38.5 ± 0.1 g, initial weight) were stocked into each of 16 tanks in a recirculating aquaculture system. A fishmeal-based diet (100% FM) was used as the control treatment and was compared with three test diets where: (1) fishmeal was partially (50%) replaced with defatted mealworm meal, Tenebrio molitor (50% DMM), (2) fishmeal was fully replaced with defatted mealworm meal (100% DMM), and (3) fishmeal was partially replaced with whole lesser mealworm meal, Alphitobius diaperinus (50% WMM). All substitutions were done on a crude protein basis. Each of the four experimental diets was evaluated in quadruplicate tanks as part of randomized design. The results indicated that Atlantic salmon showed high survival (greater or equal to 98.8%), and no significant difference in final growth, feed efficiency, feces stability and condition indices. Hepatosomatic index was lower in fish fed 100% DMM and 50% WMM when compared to fish fed the control diet (100% FM). Whole-body proximate and amino acid compositions were not statistically different between treatments, while essential fatty acids, including linolenic, eicosapentaenoic acid, and homo-a-linolenic, were lower in fish fed 100% DMM. Plasma parameters (total protein, alanine aminotransferase, alkaline phosphatase, and total iron-binding capacity), hepatic peroxide, and antioxidant enzymes were not significantly affected by dietary substitutions, whereas plasma immunoglobulin M showed significantly higher levels in fish fed 50% DMM and 100% DMM when compared to fish fed the control diet (100% FM). The inclusion of mealworm meals significantly impacted the overall microbiome composition but not the richness and evenness of the salmon digesta microbiomes compared to control. The most common genus in all treatments was Pseudomonas, which has been previously shown to have both commensal and pathogenic members. The relative expressions of growth (IGF-I) and protein synthesis (TIPRL) were not significantly different between the treatments, whereas immunoglobulin genes (IgM, IgD, and IgT) were significantly upregulated in fish fed the DMM diets when compared to fish fed the control diet. Overall, this study suggests that the mealworm meals tested could be suitable alternatives to fishmeal in the diet of Atlantic salmon.

Experiences of discrimination are associated with microbiome and transcriptome alterations in the gut.

Discrimination is a recognized psychosocial stressor that has been linked to various negative health outcomes. This study explored the impact of discrimination on gut health, specifically focusing on microbiome changes, predicted metagenomic differences, transcriptomic profiles, and the potential for using a multi-omic approach to predict discrimination to identify discrimination status for an individual. Methods: We conducted a comprehensive investigation involving male and premenopausal female participants, using the Everyday Discrimination Scale to classify them into either high or low discrimination. Multiple questionnaires were administered to evaluate participants' physiological, psychological, and perceived stressors. Two diet questionnaires were also administered. Stool samples were collected for microbiome analysis and RNA sequencing. Microbial composition changes were analyzed using the Shannon index and Chao1 richness estimator for alpha diversity and the Aitchison distance metric for beta diversity. Differential abundance was evaluated using MaAsLin2, followed by metatranscriptomics sequencing and annotation. A multi-omic approach utilizing random forest was used to assess the predictability of discrimination. The study results showed that high discrimination was linked to higher gut microbiome species richness (Chao1, p = 0.02) and significant beta diversity differences (p = 0.04). Prevotella and Ruminococcaceae were both less abundant in the high discrimination group. High discrimination participants also reported higher levels of depression, anxiety, perceived stress, early life adversity, visceral sensitivity, and neuroticism than those in the low discrimination group. Gene expression analysis revealed distinctive patterns, with significant changes in genes associated with environmental sensing (two-component system) and metabolic pathways. In a plot comparing gene transcription to DNA content, certain genes showed higher expression levels in participants who experienced both high and low levels of discrimination. Our random forest classifier demonstrated the capability to accurately differentiate individuals with high and low discrimination in our training cohort (AUC = 0.91). These findings illuminate the substantial impact of discrimination on gut health, encompassing microbiome composition, gene expression, and functional pathways. These findings suggest that discrimination is associated with internal biological changes that can be associated with negative health outcomes, opening research to examine novel pathways that can be used to mitigate the negative health effects of discrimination.

Altered composition of the Indonesian gut microbiome and heavy metal resistance genes abundance in response to heavy metal exposure

Altered composition of the Indonesian gut microbiome and heavy metal resistance genes abundance in response to heavy metal exposure

Altered composition of the Indonesian gut microbiome and heavy metal resistance genes abundance in response to heavy metal exposure

Altered composition of the Indonesian gut microbiome and heavy metal resistance genes abundance in response to heavy metal exposure

The tumoral microbiome of pancreatic intraductal papillary mucinous neoplasm: A single-center retrospective cohort study.

Pancreatic intraductal papillary mucinous neoplasm (IPMN) is one of the most common precancerous lesions of pancreatic carcinoma. Studies have found that the tumoral microbiome has an important influence on pancreatic carcinoma. However, the tumoral microbiome of IPMNs has rarely been explored. Tumoral microbiome gene sequencing was carried out using 16 specimens of IPMN and 45 specimens of IPMN with associated invasive carcinoma (IPMN-IC) by 2bRAD sequencing for microbiome. The profile of the tumoral microbiome was summarized. Associations of the tumoral microbiome with disease grade, histological subtype, and prognosis were analyzed. A total of 598 species of microbes were identified, comprising 228 genera, 109 families, 60 orders, 29 classes, 14 phyla, and 2 kingdoms. The genus Pseudomonas was detected more frequently and had higher relative abundance in IPMN-ICs; Alcaligenes faecalis was detected with higher relative abundance in IPMNs. Bifidobacterium pseudolongum had a higher relative abundance in the IPMN-IC group, regardless of histological subtype. Moreover, among patients with IPMN-ICs, those with a high relative abundance of B.pseudolongum had better overall survival than those with a low relative abundance. Patients who were positive for Staphylococcus aureus or Mycolicibacillus koreensis had shorter survival. The presence of S.aureus was an independent risk factor for poor prognosis. There are enriching tumoral microbes in IPMN. The tumoral microbiome of IPMN is different from that of IPMN-IC.

Noninvasive sampling of the small intestinal chyme for microbiome, metabolome and antimicrobial resistance genes in dogs, a proof of concept

BackgroundThe gastrointestinal microbiome and metabolome vary greatly throughout the different segments of the gastrointestinal tract, however current knowledge of gastrointestinal microbiome and metabolome in health and disease is limited to fecal samples due to ease of sampling. The engineered Small Intestinal MicroBiome Aspiration (SIMBA™) capsule allows specific sampling of the small intestine in humans. We aimed to determine whether administration of SIMBA™ capsules to healthy beagle dogs could reliably and safely sample the small intestinal microbiome and metabolome when compared to their fecal microbiome and metabolome.ResultsEleven beagle dogs were used for the study. Median transit time of capsules was 29.93 h (range: 23.83–77.88). Alpha diversity, as measured by the Simpson diversity, was significantly different (P = 0.048). Shannon diversity was not different (P = 0.114). Beta diversity results showed a significant difference between capsule and fecal samples regarding Bray–Curtis, weighted and unweighted unifrac (P = 0.002) and ANOSIM distance metric s (R = 0.59, P = 0.002). In addition to observing a statistically significant difference in the microbial composition of capsules and feces, distinct variation in the metabolite profiles was seen between the sample types. Heat map analysis showed 16 compounds that were significantly different between the 2 sampling modes (adj-P value ranged between 0.004 and 0.036) with 10 metabolites more abundant in the capsule than in the feces and 6 metabolites more abundant in the feces compared to the capsules.ConclusionsThe engineered Small Intestinal MicroBiome Aspiration (SIMBA™) capsule was easy and safe to administer to dogs. Microbiome and metabolome analysis from the capsule samples were significantly different than that of the fecal samples and were like previously published small intestinal microbiome and metabolome composition.Graphical abstract

An accurate aging clock developed from large-scale gut microbiome and human gene expression data

Accurate measurement of the biological markers of the aging process could provide an "aging clock" measuring predicted longevity and enable the quantification of the effects of specific lifestyle choices on healthy aging. Using machine learning techniques, we demonstrate that chronological age can be predicted accurately from (1) the expression level of human genes in capillary blood and (2) the expression level of microbial genes in stool samples. The latter uses a very large metatranscriptomic dataset, stool samples from 90,303 individuals, which arguably results in a higher quality microbiome-aging model than prior work. Our analysis suggests associations between biological age and lifestyle/health factors, e.g., people on a paleo diet or with IBS tend to have higher model-predicted ages and people on a vegetarian diet tend to have lower model-predicted ages. We delineate the key pathways of systems-level biological decline based on the age-specific features of our model.