Antimicrobial Activity of Metals and Metalloids.

Competition shapes evolution. Toxic metals and metalloids have exerted selective pressure on life since the rise of the first organisms on the Earth, which has led to the evolution and acquisition of resistance mechanisms against them, as well as mechanisms to weaponize them. Microorganisms exploit antimicrobial metals and metalloids to gain competitive advantage over other members of microbial communities. This exerts a strong selective pressure that drives evolution of resistance. This review describes, with a focus on arsenic and copper, how microorganisms exploit metals and metalloids for predation and how metal- and metalloid-dependent predation may have been a driving force for evolution of microbial resistance against metals and metalloids.

Fungi and bacteria in the beds of rural and urban infants correlate with later risk of atopic diseases.

INTRODUCTION: Rural children have a lower risk of asthma and atopic diseases than urban children. However, whether indoor microbiota in non-farming rural homes provides protection is unclear. METHODS: Here, we examine if microbes in the beds of rural and urban infants are associated with later development of atopic diseases. We studied fungi and bacteria in the beds of 6-month-old infants (n = 514) in association with the risk of asthma, allergic rhinitis, eczema and aeroallergen sensitization at 6 years of age in the prospective COPSAC2010 cohort. RESULTS: Both fungal and bacterial diversity were lower in the beds of children, who later developed allergic rhinitis (-0.22 [-0.43,-0.01], padj = .04 and -.24 [-0.42,-0.05], padj = .01 respectively) and lower bacterial richness was discovered in beds of children later developing asthma (-41.34 [-76.95,-5.73], padj = .02) or allergic rhinitis (-45.65 [-81.19,-10.10], padj = .01). Interestingly, higher fungal diversity and richness were discovered in the beds of children developing eczema (0.23 [0.02,0.43], padj = .03 and 29.21 [1.59,56.83], padj = .04 respectively). We defined a limited set of fungal and bacterial genera that predicted rural/urban environment. Some rural-associated bacterial genera such as Romboutsia and Bacillus and fungal genera Spegazzinia and Physcia were also associated with reduced risk of diseases, including eczema. These fungal and bacterial fingerprints predicting the living environment were associated with asthma and allergic rhinitis, but not eczema, with rural compositions being protective. The bed dust bacteria mediated 27% of the protective association of a rural living environment for allergic rhinitis (p = .04). CONCLUSIONS: Bed dust microbes can be differentially associated with airway- and skin-related diseases. The differing bed dust microbiota between rural and urban infants may influence their later risk of asthma and allergic rhinitis.

Watching Videos of Colonoscopies and Receiving Interpretations Reduce Pain and Anxiety While Increasing the Satisfaction of Patients.

BACKGROUND: Pain associated with colonoscopies is a major barrier to patients participating in colorectal cancer screenings. While sedation and analgesia are used to reduce pain during the procedure, they are associated with increased complications and costs. Thus, it is necessary to identity novel techniques to relieve pain in a safe and cost-effective way. AIMS: To test whether watching real-time videos of colonoscopies while receiving detailed interpretations of the procedures reduces pain and anxiety and increases a patient's satisfaction. METHODS: Patients were randomized into three groups including a group who watched real-time videos of their colonoscopies (Group A), a group who watched real-time videos of their colonoscopies while receiving detailed interpretations of the procedures from the endoscopists (Group B), and a group who did not receive either method (Group C). RESULTS: Pain and anxiety scores were significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) lower in Groups A and B compared to Group C. Additionally, significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) increased satisfaction was observed in Groups A and B compared to Group C. There were no statistically significant differences observed in the pain and anxiety scores when comparing Groups A and B. However, the overall satisfaction score was significantly ([Formula: see text]) higher in Group B compared to Group A. CONCLUSIONS: Real-time videos of colonoscopies as well as videos along with detailed interpretations of the procedures decrease pain and anxiety while improving satisfaction in patients undergoing colonoscopies without sedation. Videos combined with interpretations lead to a greater increase in patient satisfaction.

Papio spp. Colon microbiome and its link to obesity in pregnancy.

INTRODUCTION: Gut microbial communities are critical players in the pathogenesis of obesity. Pregnancy is associated with increased bacterial load and changes in gut bacterial diversity. Sparse data exist regarding composition of gut microbial communities in obesity combined with pregnancy. MATERIAL AND METHODS: Banked tissues were collected under sterile conditions during necropsy, from three non-obese (nOb) and four obese (Ob) near-term pregnant baboons. Sequences were assigned taxonomy using the Ribosomal Database Project classifier. Microbiome abundance and its difference between distinct groups were assessed by a nonparametric test. RESULTS: Three families predominated in both the nOb and Ob colonic microbiome: Prevotellaceae (25.98% and 32.71% respectively), Ruminococcaceae (12.96% and 7.48%), and Lachnospiraceae (8.78% and 11.74%). Seven families of the colon microbiome displayed differences between Ob and nOb groups. CONCLUSION: Changes in gut microbiome in pregnant obese animals open the venue for dietary manipulation in pregnancy.

A role for copper in protozoan grazing - two billion years selecting for bacterial copper resistance.

The Great Oxidation Event resulted in integration of soft metals in a wide range of biochemical processes including, in our opinion, killing of bacteria by protozoa. Compared to pressure from anthropologic copper contamination, little is known on impacts of protozoan predation on maintenance of copper resistance determinants in bacteria. To evaluate the role of copper and other soft metals in predatory mechanisms of protozoa, we examined survival of bacteria mutated in different transition metal efflux or uptake systems in the social amoeba Dictyostelium discoideum. Our data demonstrated a strong correlation between the presence of copper/zinc efflux as well as iron/manganese uptake, and bacterial survival in amoebae. The growth of protozoa, in turn, was dependent on bacterial copper sensitivity. The phagocytosis of bacteria induced upregulation of Dictyostelium genes encoding the copper uptake transporter p80 and a triad of Cu(I)-translocating PIB -type ATPases. Accumulated Cu(I) in Dictyostelium was monitored using a copper biosensor bacterial strain. Altogether, our data demonstrate that Cu(I) is ultimately involved in protozoan predation of bacteria, supporting our hypothesis that protozoan grazing selected for the presence of copper resistance determinants for about two billion years.

Bacterial resistance to arsenic protects against protist killing.

Protists kill their bacterial prey using toxic metals such as copper. Here we hypothesize that the metalloid arsenic has a similar role. To test this hypothesis, we examined intracellular survival of Escherichia coli (E. coli) in the amoeba Dictyostelium discoideum (D. discoideum). Deletion of the E. coli ars operon led to significantly lower intracellular survival compared to wild type E. coli. This suggests that protists use arsenic to poison bacterial cells in the phagosome, similar to their use of copper. In response to copper and arsenic poisoning by protists, there is selection for acquisition of arsenic and copper resistance genes in the bacterial prey to avoid killing. In agreement with this hypothesis, both copper and arsenic resistance determinants are widespread in many bacterial taxa and environments, and they are often found together on plasmids. A role for heavy metals and arsenic in the ancient predator-prey relationship between protists and bacteria could explain the widespread presence of metal resistance determinants in pristine environments.

Clinical study on the relationship between liver cirrhosis, ascites, and hyponatremia.

BACKGROUND: Cirrhosis is a common liver disease, and ascites is one of the common clinical conditions. However, the clinical manifestations of ascites combined with hyponatremia as a high-risk condition and its relationship to patient prognosis have not been fully studied. AIM: To explore the clinical manifestations, prognostic factors, and relationships of ascites with hyponatremia in patients with cirrhosis to provide better diagnostic and treatment strategies. METHODS: In this study, we retrospectively analyzed the clinical data of 150 patients diagnosed with cirrhosis and ascites between 2017 and 2022. Patients were divided into two groups: ascites combined with hyponatremia group and ascites group. We compared the general characteristics, degree of hyponatremia, complications, treatment, and prognosis between the two groups. RESULTS: In the study results, patients in the ascites combined with hyponatremia group showed an older average age (58.2 ± 8.9 years), 64.4% were male, and had a significantly longer hospitalization time (12.7 ± 5.3 d). Hyponatremia was more severe in this group, with a mean serum sodium concentration of 128.5 ± 4.3 mmol/L, which was significantly different from the ascites group of 137.6 ± 2.1 mmol/L. Patients with ascites and hyponatremia were more likely to develop hepatic encephalopathy (56.2% vs 39.0%), renal impairment (45.2% vs 28.6%) and infection (37.0% vs 23.4%). Regarding treatment, this group more frequently used diuretics (80.8% vs 62.3%) and salt supplements (60.3% vs 38.9%). Multiple logistic regression analysis identified older age [Odds ratio (OR) = 1.06, P = 0.025] and male gender (OR = 1.72, P = 0.020) as risk factors for hyponatremia combined with ascites. Overall, patients with ascites and hyponatremia present a clear high-risk status, accompanied by severe complications and poor prognosis. CONCLUSION: In patients with cirrhosis, ascites with hyponatremia is a high-risk condition that is often associated with severe complications.

Cyanidin-3-O-glucoside alleviates ethanol-induced liver injury by promoting mitophagy in a Gao-binge mouse model of alcohol-associated liver disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is a leading cause of liver disease-related deaths worldwide. Unfortunately, approved medications for the treatment of this condition are quite limited. One promising candidate is the anthocyanin, Cyanidin-3-O-glucoside (C3G), which has been reported to protect mice against hepatic lipid accumulation, as well as fibrosis in different animal models. However, the specific effects and mechanisms of C3G on ALD remain to be investigated. EXPERIMENTAL APPROACH: In this report, a Gao-binge mouse model of ALD was used to investigate the effects of C3G on ethanol-induced liver injury. The mechanisms of these C3G effects were assessed using AML12 hepatocytes. RESULTS: C3G administration ameliorated ethanol-induced liver injury by suppressing hepatic oxidative stress, as well as through reducing hepatic lipid accumulation and inflammation. Mechanistically, C3G activated the AMPK pathway and enhanced mitophagy to eliminate damaged mitochondria, thus reducing mitochondria-derived reactive oxidative species in ethanol-challenged hepatocytes. CONCLUSIONS: The results of this study indicate that mitophagy plays a potentially important role underlying the hepatoprotective action of C3G, as demonstrated in a Gao-binge mouse model of ALD. Accordingly, C3G may serve as a promising, new therapeutic drug candidate for use in ALD.

Interspecific interactions facilitate keystone species in a multispecies biofilm that promotes plant growth.

Microorganisms colonizing plant roots co-exist in complex, spatially structured multispecies biofilm communities. However, little is known about microbial interactions and the underlying spatial organization within biofilm communities established on plant roots. Here, a well-established four-species biofilm model (Stenotrophomonas rhizophila, Paenibacillus amylolyticus, Microbacterium oxydans, and Xanthomonas retroflexus, termed as SPMX) was applied to Arabidopsis roots to study the impact of multispecies biofilm on plant growth and the community spatial dynamics on the roots. SPMX co-culture notably promoted root development and plant biomass. Co-cultured SPMX increased root colonization and formed multispecies biofilms, structurally different from those formed by monocultures. By combining 16S rRNA gene amplicon sequencing and fluorescence in situ hybridization with confocal laser scanning microscopy, we found that the composition and spatial organization of the four-species biofilm significantly changed over time. Monoculture P. amylolyticus colonized plant roots poorly, but its population and root colonization were highly enhanced when residing in the four-species biofilm. Exclusion of P. amylolyticus from the community reduced overall biofilm production and root colonization of the three species, resulting in the loss of the plant growth-promoting effects. Combined with spatial analysis, this led to identification of P. amylolyticus as a keystone species. Our findings highlight that weak root colonizers may benefit from mutualistic interactions in complex communities and hereby become important keystone species impacting community spatial organization and function. This work expands the knowledge on spatial organization uncovering interspecific interactions in multispecies biofilm communities on plant roots, beneficial for harnessing microbial mutualism promoting plant growth.

Co-localization of antibiotic resistance genes is widespread in the infant gut microbiome and associates with an immature gut microbial composition.

BACKGROUND: In environmental bacteria, the selective advantage of antibiotic resistance genes (ARGs) can be increased through co-localization with genes such as other ARGs, biocide resistance genes, metal resistance genes, and virulence genes (VGs). The gut microbiome of infants has been shown to contain numerous ARGs, however, co-localization related to ARGs is unknown during early life despite frequent exposures to biocides and metals from an early age. RESULTS: We conducted a comprehensive analysis of genetic co-localization of resistance genes in a cohort of 662 Danish children and examined the association between such co-localization and environmental factors as well as gut microbial maturation. Our study showed that co-localization of ARGs with other resistance and virulence genes is common in the early gut microbiome and is associated with gut bacteria that are indicative of low maturity. Statistical models showed that co-localization occurred mainly in the phylum Proteobacteria independent of high ARG content and contig length. We evaluated the stochasticity of co-localization occurrence using enrichment scores. The most common forms of co-localization involved tetracycline and fluoroquinolone resistance genes, and, on plasmids, co-localization predominantly occurred in the form of class 1 integrons. Antibiotic use caused a short-term increase in mobile ARGs, while non-mobile ARGs showed no significant change. Finally, we found that a high abundance of VGs was associated with low gut microbial maturity and that VGs showed even higher potential for mobility than ARGs. CONCLUSIONS: We found that the phenomenon of co-localization between ARGs and other resistance and VGs was prevalent in the gut at the beginning of life. It reveals the diversity that sustains antibiotic resistance and therefore indirectly emphasizes the need to apply caution in the use of antimicrobial agents in clinical practice, animal husbandry, and daily life to mitigate the escalation of resistance. Video Abstract.

Differential responses of the gut microbiome and resistome to antibiotic exposures in infants and adults.

Despite their crucial importance for human health, there is still relatively limited knowledge on how the gut resistome changes or responds to antibiotic treatment across ages, especially in the latter case. Here, we use fecal metagenomic data from 662 Danish infants and 217 young adults to fill this gap. The gut resistomes are characterized by a bimodal distribution driven by E. coli composition. The typical profile of the gut resistome differs significantly between adults and infants, with the latter distinguished by higher gene and plasmid abundances. However, the predominant antibiotic resistance genes (ARGs) are the same. Antibiotic treatment reduces bacterial diversity and increased ARG and plasmid abundances in both cohorts, especially core ARGs. The effects of antibiotic treatments on the gut microbiome last longer in adults than in infants, and different antibiotics are associated with distinct impacts. Overall, this study broadens our current understanding of gut resistome dynamics and the impact of antibiotic treatment across age groups.

Metagenomic evidence for co-occurrence of antibiotic, biocide and metal resistance genes in pigs.

Antibiotic-resistant pathogens constitute an escalating public health concern. Hence a better understanding of the underlying processes responsible for this expansion is urgently needed. Co-selection of heavy metal/biocide and antibiotic resistance genes (ARGs) has been suggested as one potential mechanism promoting the proliferation of antimicrobial resistance (AMR). This paper aims to elucidate this interplay and exploit differences in antibiotic usage to infer patterns of co-selection by the non-antibiotic factors metals and biocides in the context of pig farming. We examined 278 gut metagenomes from pigs with continuous antibiotic exposure, only at weaning and at no exposure. Metals as growth promoters and biocides as disinfectants are currently used with little restrictions in stock farming. The pigs under continuous antibiotic exposure displayed the highest co-occurrence of ARGs and other genetic elements while the pigs under limited use of antibiotics still showed abundant co-occurrences. Pathogens belonging to Enterobacteriaceae displayed increased co-occurrence phenomena, suggesting that this maintenance is not a random selection process from a mobilized pool but pertains to specific phylogenetic clades. These results suggest that metals and biocides displayed strong selective pressures on ARGs exerted by intensive farming, regardless of the current use of antibiotics.

Identification of potential serum exosomal microRNAs involved in acinar-ductal metaplasia that is a precursor of pancreatic cancer associated with chronic pancreatitis.

BACKGROUNDS: Due to difficulty in early diagnosis of chronic pancreatitis (CP), it is urgent to find novel biomarkers to detect CP. Exosomal microRNAs (Exo-miRNAs) located in the serum may be potential diagnostic and therapeutic targets for CP. OBJECTIVE: To identify differentially expressed Exo-miRNAs (DE-Exo-miRNAs) in the serum of CP patients, we performed a bioinformatics analysis. METHODS: The dataset GSE128508 was downloaded from the Gene Expression Omnibus (GEO) database. The analysis was carried out using BRB-ArrayTools and significance analysis of microarrays (SAM). The target genes of DE-S-Exo-miRNAs were predicted by miRWalk databases. Further gene ontology (GO) term and Kyoto Encyclopedia of Genomes (KEGG) pathway analyses were performed with plug-in ClueGO in Cytoscape software 3.7.0. Subsequently, the interaction regulatory network between encoded proteins of target genes was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and analyzed using plug-in Molecular Complex Detection (MCODE) and cytoHubba in Cytoscape software 3.7.0. RESULTS: We identified 227 DE-Exo-miRNAs in the serum. Further analysis using the miRWalk database identified 5164 target genes of these miRNAs. The protein-protein interaction (PPI) regulatory network of 1912 potential target genes for hub 10 up-regulated miRNAs with high degrees and one down-regulated miRNAs were constructed using the STRING database and Cytoscape software. The functional analysis using Cytoscape software tool highlighted that target genes involved in pancreatic cancer. Acinar-ductal metaplasia (ADM) in the inflammatory environment of CP is a precursor of pancreatic cancer. Subsequently, we constructed a network of target genes associated with ADM and their miRNAs. CONCLUSIONS: Exo-miRNAs in the serum as well as their target genes may be promising targets for the early diagnosis and treatment of CP. In addition, we identified potential Exo-miRNAs involved in ADM that is a precursor of pancreatic cancer associated with CP.

Emergent bacterial community properties induce enhanced drought tolerance in Arabidopsis.

Drought severely restricts plant production and global warming is further increasing drought stress for crops. Much information reveals the ability of individual microbes affecting plant stress tolerance. However, the effects of emergent bacterial community properties on plant drought tolerance remain largely unexplored. Here, we inoculated Arabidopsis plants in vivo with a four-species bacterial consortium (Stenotrophomonas rhizophila, Xanthomonas retroflexus, Microbacterium oxydans, and Paenibacillus amylolyticus, termed as SPMX), which is able to synergistically produce more biofilm biomass together than the sum of the four single-strain cultures, to investigate its effects on plant performance and rhizo-microbiota during drought. We found that SPMX remarkably improved Arabidopsis survival post 21-day drought whereas no drought-tolerant effect was observed when subjected to the individual strains, revealing emergent properties of the SPMX consortium as the underlying cause of the induced drought tolerance. The enhanced drought tolerance was associated with sustained chlorophyll content and endogenous abscisic acid (ABA) signaling. Furthermore, our data showed that the addition of SPMX helped to stabilize the diversity and structure of root-associated microbiomes, which potentially benefits plant health under drought. These SPMX-induced changes jointly confer an increased drought tolerance to plants. Our work may inform future efforts to engineer the emergent bacterial community properties to improve plant tolerance to drought.

The infant gut resistome associates with E. coli, environmental exposures, gut microbiome maturity, and asthma-associated bacterial composition.

Antimicrobial resistance (AMR) is an accelerating global threat, yet the nature of AMR in the gut microbiome and how AMR is acquired during early life remain largely unknown. In a cohort of 662 Danish children, we characterized the antibiotic resistance genes (ARGs) acquired during the first year of life and assessed the impacts of diverse environmental exposures on ARG load. Our study reveals a clear bimodal distribution of ARG richness that is driven by the composition of the gut microbiome, especially E. coli. ARG profiles were significantly affected by various environmental factors. Among these factors, the importance of antibiotics diminished with time since treatment. Finally, ARG load and ARG clusters were also associated with the maturity of the gut microbiome and a bacterial composition associated with increased risk of asthma. These findings broaden our understanding of AMR in early life and have critical implications for efforts to mitigate its spread.

Co-selection of antibiotic resistance genes, and mobile genetic elements in the presence of heavy metals in poultry farm environments.

Environmental selection of antibiotic resistance genes (ARGs) is considered to be caused by antibiotic or metal residues, frequently used in livestock. In this study we examined three commercial poultry farms to correlate the co-occurrence patterns of antibiotic and metal residues to the presence of ARGs. We quantified 283 ARGs, 12 mobile genetic elements (MGEs), 49 targeted antibiotics, 7 heavy metals and sequenced 16S rRNA genes. The abundance and type of ARG were significantly enriched in manure while soil harbored the most diverse bacterial community. Procrustes analysis displayed significant correlations between ARGs/MGEs and the microbiome. Cadmium (Cd), arsenic (As), zinc (Zn), copper (Cu) and lead (Pb) were responsible for a majority of positive correlations to ARGs when compared to antibiotics. Integrons and transposons co-occurred with ARGs corresponding to 9 classes of antibiotics, especially Class1 integrase intI-1LC. Redundancy analysis (RDA) and Variance partitioning analysis (VPA) showed that antibiotics, metals, MGEs and bacteria explain solely 0.7%, 5.7%, 12.4%, and 21.9% of variances of ARGs in the microbial community, respectively. These results suggested that bacterial composition and horizontal gene transfer were the major factors shaping the composition of ARGs; Metals had a bigger effect on ARG profile than detected antibiotics in this study.

Efficient Production of Pyruvate Using Metabolically Engineered Lactococcus lactis.

Microbial production of commodity chemicals has gained increasing attention and most of the focus has been on reducing the production cost. Selecting a suitable microorganism, which can grow rapidly on cheap feedstocks, is of key importance when developing an economically feasible bioprocess. We chose Lactococcus lactis, a well-characterized lactic acid bacterium, as our microbial host to produce pyruvate, which is a commodity chemical with various important applications. Here we report the engineering of Lactococcus lactis into becoming an efficient microbial platform for producing pyruvate. The strain obtained, FS1076 (MG1363 Δ3 ldh Δpta ΔadhE Δals), was able to produce pyruvate as the sole product. Since all the competitive pathways had been knocked out, we achieved growth-coupled production of pyruvate with high yield. More than 80 percent of the carbon flux was directed toward pyruvate, and a final titer of 54.6 g/L was obtained using a fed-batch fermentation setup. By introducing lactose catabolism into FS1076, we obtained the strain FS1080, which was able to generate pyruvate from lactose. We then demonstrated the potential of FS1080 for valorizing lactose contained in dairy side-streams, by achieving a high titer (40.1 g/L) and high yield (78.6%) of pyruvate using residual whey permeate (RWP) as substrate. The results obtained, show that the L. lactis platform is well-suited for transforming lactose in dairy waste into food-grade pyruvate, and the yields obtained are the highest reported in the literature. These results demonstrate that it is possible to achieve sustainable bioconversion of waste products from the dairy industry (RWP) to valuable products.

The microbiome of captive hamadryas baboons.

BACKGROUND: The hamadryas baboon (Papio hamadryas) is a highly social primate that lives in complex multilevel societies exhibiting a wide range of group behaviors akin to humans. In contrast to the widely studied human microbiome, there is a paucity of information on the host-associated microbiomes of nonhuman primates (NHPs). Here, our goal was to understand the microbial composition throughout different body sites of cohabiting baboons. RESULTS: We analyzed 170 oral, oropharyngeal, cervical, uterine, vaginal, nasal and rectal samples from 16 hamadryas baboons via 16S rRNA gene sequencing. Additionally, raw Miseq sequencing data from 1041 comparable publicly available samples from the human oral cavity, gut and vagina were reanalyzed using the same pipeline. We compared the baboon and human microbiome of the oral cavity, gut and vagina, showing that the baboon microbiome is distinct from the human. Baboon cohabitants share similar microbial profiles in their cervix, uterus, vagina, and gut. The oral cavity, gut and vagina shared more bacterial amplicon sequence variants (ASVs) in group living baboons than in humans. The shared ASVs had significantly positive correlations between most body sites, suggesting a potential bacterial exchange throughout the body. No significant differences in gut microbiome composition were detected within the maternity line and between maternity lines, suggesting that the offspring gut microbiota is shaped primarily through bacterial exchange among cohabitants. Finally, Lactobacillus was not so predominant in baboon vagina as in the human vagina but was the most abundant genus in the baboon gut. CONCLUSIONS: This study is the first to provide comprehensive analyses of the baboon microbiota across different body sites. We contrast this to human body sites and find substantially different microbiomes. This group of cohabitating baboons generally showed higher microbial diversity and remarkable similarities between body sites than were observed in humans. These data and findings from one group of baboons can form the basis of future microbiome studies in baboons and be used as a reference in research where the microbiome is expected to impact human modeling with baboons.

Environmental shaping of the bacterial and fungal community in infant bed dust and correlations with the airway microbiota.

BACKGROUND: From early life, children are exposed to a multitude of environmental exposures, which may be of crucial importance for healthy development. Here, the environmental microbiota may be of particular interest as it represents the interface between environmental factors and the child. As infants in modern societies spend a considerable amount of time indoors, we hypothesize that the indoor bed dust microbiota might be an important factor for the child and for the early colonization of the airway microbiome. To explore this hypothesis, we analyzed the influence of environmental exposures on 577 dust samples from the beds of infants together with 542 airway samples from the Copenhagen Prospective Studies on Asthma in Childhood2010 cohort. RESULTS: Both bacterial and fungal community was profiled from the bed dust. Bacterial and fungal diversity in the bed dust was positively correlated with each other. Bacterial bed dust microbiota was influenced by multiple environmental factors, such as type of home (house or apartment), living environment (rural or urban), sex of siblings, and presence of pets (cat and/or dog), whereas fungal bed dust microbiota was majorly influenced by the type of home (house or apartment) and sampling season. We further observed minor correlation between bed dust and airway microbiota compositions among infants. We also analyzed the transfer of microbiota from bed dust to the airway, but we did not find evidence of transfer of individual taxa. CONCLUSIONS: Current study explores the influence of environmental factors on bed dust microbiota (both bacterial and fungal) and its correlation with airway microbiota (bacterial) in early life using high-throughput sequencing. Our findings demonstrate that bed dust microbiota is influenced by multiple environmental exposures and could represent an interface between environment and child. Video Abstract.

Heavy metal exposure causes changes in the metabolic health-associated gut microbiome and metabolites.

BACKGROUND: Exposure to arsenic and cadmium is common. Epidemiological and animal studies have suggested that exposure to these two heavy metals can cause metabolic health problems, including type 2 diabetes (T2DM). It has been hypothesized that T2DM could be mediated through the gut microbiome and the metabolites it produces. Although many studies have investigated the association between the gut microbiome and T2DM, few have focused on the connection to arsenic and cadmium. RESULTS: We applied 16S rRNA gene amplicon sequencing and untargeted LC-MS/MS metabolomics to examine the changes in the gut microbiome and metabolite profiles of exposed mice to relevant levels of cadmium and arsenic in the drinking water over two weeks. Cadmium chloride (Cd) exposure significantly changed the mice gut microbiome and resulted in a significantly lower microbial diversity whereas sodium arsenite (As) caused a non-significant decrease in microbial diversity. For Cd and As treatment respectively, we identified 5 and 2 phyla with significant changes and 42 and 24 genera. Bacterial genera that were observed to decline upon both treatments, included several butyrate-producers. Both As and Cd treatment perturbed the metabolome significantly, with 50 ppm Cd compound exposure having the greatest effect when compared to 50 ppm As compound exposure. Two unidentified features were differentially abundant in the As group, while 33 features changed in the Cd group. Differential abundance analysis of all bile acid associated molecular components showed differences under both treatments. Finally, integrative network analysis via bipartite correlation networks suggested that several genera, including the metabolically important Blautia, Eisenbergiella, Clostridium_XlVa, etc. declined in numbers of metabolite interactions. CONCLUSIONS: These results demonstrated that As and Cd exposure caused significant changes to the gut microbiome and metabolome by affecting bile acids, amino acids and taxa associated with metabolic health.