Gut Flora Research Articles

Gut Check: Microbiota and Obesity in Mice Exposed to Polystyrene Microspheres.

Gut microbes appeared to play a role in the obesity outcomes observed in mice fed manufactured polystyrene microspheres.

Comparative transcriptional analyses of the striatum in the chronic social defeat stress model in C57BL/6J male mice and the gut microbiota-dysbiosis model in Kumming mice

Depression is a complex disorder with multiple contributing factors, and chronic stress has previously been recognized as a major causative factor, while gut microbes have also been found to be involved in depression recently. However, gene expression in depression models with different etiologies is unclear. Here, we compared the transcriptomes of the striatum in chronic social defeat stress (CSDS) model of C57BL/6J male mice and fecal microbiota transplant (FMT) model of Kumming male mice. We found that the proportion of shared differentially expressed genes (DEGs) between the two models was only 24 %. The specific DEGs of FMT model were enriched in immune and inflammatory, and are associated with changes in vascular and ciliated ependymal cells. The specific DEGs of CSDS model were enriched in neuron and synapse. The results of network analysis suggested the expression patterns and biological function of depressive-like behaviors-related modules in the two models are different. Further, the alternative splicing events of CSDS are more than FMT. Our results suggested models of depression induced by different etiologies differ significantly in gene expression and biological function. Our study also suggested us to pay attention to the characteristics of models of depression of different etiologies and provided a more comprehensive understanding of the heterogeneity of depression.

Association between seizure reduction during ketogenic diet treatment of epilepsy and changes in circulatory metabolites and gut microbiota composition

The ketogenic diet (KD) is a high fat, sufficient protein, and low carbohydrate dietary therapy for drug-resistant epilepsy. The underlying mechanisms of action of the KD remain unclear. In mice, the microbiota is necessary for the anti-seizure effect and specific microbes influence circulatory levels of metabolites that are linked to seizure reduction. However, it remains unclear which changes are linked to seizure reduction in patients with epilepsy. We analysed the serum metabolome of children with drug-resistant epilepsy (n=14) before and after three months on KD. Metabolomic changes were correlated to the gut microbiome and treatment outcome, i.e., seizure reduction. In this prospective observational study, we uncovered associations between microbial species and serum metabolites that correlated with seizure reduction. Plasmalogens were most strongly linked to seizure reduction and had significant positive correlations with several gut microbes (e.g., Faecalibacterium prausnitzii, Alistipes communis, Alistipes shahii, and Christensenella minuta) while significant negative correlations were found for five strains of Escherichia coli. Infant-type Bifidobacteria correlated negatively with other metabolites associated with seizure reduction. The microbes and metabolites identified here may contribute to the therapeutic effect of the KD in children with drug-resistant epilepsy. Several of these metabolites (e.g., plasmalogens) play important roles in neurobiology and may influence seizures. Based on our findings, anti-seizure therapeutic strategies could be developed involving the targeted manipulation of the gut microbiota and/or its metabolites. This study was supported by the Swedish Brain Foundation, Margarethahemmet Society, Sunnerdahls Handikappfond, Stockholm County Council Research Funds, and Linnea & Josef Carlssons Foundation.

Unraveling the causation of flatulence on silver pomfret after starvation aquaculture involved in intestinal microbiota structure, enzyme, and histology

During periods of starvation aquaculture, silver pomfret often suffer from flatulence and lateral flapping, which prevents them from refeeding and dying. Despite existing research on this phenomenon, the understanding of the associated changes in the intestine remains limited. This study aimed to investigate flatulence in silver pomfret during starvation. We conducted a comprehensive analysis of the enzymatic activity, histology, and microbial communities in the gut. Through the examination of 28 samples, we found that the trigger for flatulence under starvation does not appear to be enzyme activity but rather gut microbes. During periods of food deprivation, the fish often ingest air bubbles, leading to an increased proportion of aerobic bacteria. We observed a notable shift in the β - diversity of the intestinal microbial community in flatulent fish, accompanied by a significant decrease in network stability. A marked enrichment in functional microbes was noted, which contributed to increased activities related to CO2 production. In conclusion, this study provides novel insights into the mechanism of flatulence in silver pomfret during starvation stress, highlighting the role of microbial composition. These findings have significant implications for improving aquaculture practices by addressing microbial management.

Metagenomic analysis reveals effects of gut microbiome in response to neoadjuvant chemoradiotherapy in advanced rectal cancer

Neoadjuvant chemoradiotherapy can enhance survival rate of patients with advanced rectal cancer, but its effectiveness varies considerably. Previous studies have indicated that gut microbes may serve as biomarkers for predicting treatment efficacy. However, the specific roles of the gut microbiome in patients who have good response to nCRT remains unclear. In this study, shotgun metagenomic sequencing technology was used to analyze the fecal microbiome of patients with varying responses to nCRT. Our findings revealed that beneficial intestinal bacteria and genes from different metabolic pathways (carbohydrate metabolism, amino acid metabolism, and sulfur metabolism) were significantly enriched in patients with good response. Additionally, causal relationship in which microbial-derived GDP-D-rhamnose and butyrate could influence the response to nCRT was clarified. Our results offered new insights into the different response to nCRT, and provided valuable reference points for improving the effectiveness of nCRT in patients with advanced colorectal cancer.

The gut microbiome in patients with Cushing’s disease affects depression- and anxiety-like behavior in mice

BackgroundDepression and anxiety significantly impact the quality of life in individuals with Cushing’s disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.ResultsThe gut bacterial phenotype of patients with Cushing’s disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2–14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing’s disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing’s disease with different levels of depression and anxiety.ConclusionsIn summary, this research enhances our current understanding of how gut microbes in patients with Cushing’s disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches.5dhu2eBu8fQWFpV1_knqDYVideo

Altered intestinal microbiota and fecal metabolites in patients with latent and active pulmonary tuberculosis.

Pulmonary tuberculosis (PTB) is the main cause of infection-related mortality and the most common infectious disease that develops resistance to antibiotics. Gut microbiota and their associated metabolites are assumed to induce and influence the development of PTB. However, the alterations of gut microbiota and metabolites in TB patients is currently unclear. Fecal samples were collected from 13 PTB patients, 13 LTBI patients, and 13 healthy controls (HC). 16S rRNA sequencing and metabolomics were used to analyze the changes in the intestinal microbiota and the composition of fecal metabolites in groups. Our findings indicated that the α-diversity of the gut microbiota in patients with PTB and LTBI decreases compared to HC, and at the phylum level, the relative abundance of Firmicutes decreases and the relative abundance of Bacteroides increases. And six genera were notably enriched in PTB patients and four in LTBI patients. Metabolomic analysis showed alterations in metabolite levels, such as short-chain fatty acids and amino acids. we comprehensively explored the changes in the gut microbes and fecal metabolites in patients with PTB and LTBI from the perspective of the gut microbiota, which may provide potential diagnostic biomarkers and therapeutic targets for TB diagnosis and treatment.

MicroRNA-specific targets for neuronal plasticity, neurotransmitters, neurotrophic factors, and gut microbes in the pathogenesis and therapeutics of depression

Depression is of great concern because of the huge burden, and it is impacted by various epigenetic modifications, e.g., histone modification, covalent modifications in DNA, and silencing mechanisms of non-coding protein genes, e.g., microRNAs (miRNAs). MiRNAs are a class of endogenous non-coding RNAs. Alternations in specific miRNAs have been observed both in depressive patients and experimental animals. Also, miRNAs are highly expressed in the central nervous system and can be delivered to different tissues via tissue-specific exosomes. However, the mechanism of miRNAs' involvement in the pathological process of depression is not well understood. Therefore, we summarized and discussed the role of miRNAs in depression. Conclusively, miRNAs are involved in the pathology of depression by causing structural and functional changes in synapses, mediating neuronal regeneration, differentiation, and apoptosis, regulating the gut microbes and the expression of various neurotransmitters and BDNF, and mediating inflammatory and immune responses. Moreover, miRNAs can predict the efficacy of antidepressant medications and explain the mechanism of action of antidepressant drugs and aerobic exercise to prevent and assist in treating depression.

Lactobacillus plantarum LP104 improved intestinal and brain inflammation by modulating TLR4 pathway and gut flora in alcohol liver injury mice

In this study, Lactobacillus plantarum LP104 (LP104) originating from kimchi was treated to C57BL/6N mice fed a chronic-plus-single-binge ethanol diet for ten days, aiming to evaluate the effects of the probiotics on intestinal and brain inflammation in the alcohol-induced liver injury model. Dietary supplementation with LP104 significantly reduced the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in alcoholic hepatic injury mice. The 16S rDNA sequencing results inferred that LP104 modulated the intestinal microbiota by depleting inflammation-related bacterial genera Proteobacteria and enriching Lactobacillus and Roseburia. Furthermore, LP104 intervention attenuated alcohol-induced gut inflammation by the TLR4 signaling pathway, which regulated the expressions of intestinal tight junction proteins such as ZO-1, Claudin-1 and Occludin. Subsequently, LP104 intake exerted neuroprotection by restoring neurotrophic factor levels and the blood-brain barrier (BBB) function to decrease lipopolysaccharide (LPS) levels in the serum. The western blotting results suggested LP104 ameliorated alcohol-induced brain inflammation by inhibiting the LPS/TLR4 signaling pathway in mice. Spearman's correlation analysis demonstrated that differential intestinal bacterial taxa were connected with the expressions of inflammation-related proteins in both gut and brain of alcohol liver injury mice.

Fucosylated chondroitin sulfate alleviates diet-induced obesity by modulating intestinal lipid metabolism and colonic microflora

Fucosylated chondroitin sulfate from Pearsonothuria graeffei (FCS-Pg), a natural macromolecular polysaccharide, has been proven to prevent obesity, but its underlying molecular mechanism is still unclear. C57BL/6 J mice fed on high fat diet (HFD) were administered FCS-Pg lasting for ten weeks. The results demonstrated that FCS-Pg supplementation reduced body weight with dosage manner compared with HFD group. The expressions of intestinal lipid synthesis related proteins such as cluster of differentiation 36 (CD36) in FCS-Pg group were lower than those in the HFD group. Compared with the normal group, HFD caused gut microbiota disorder in the colon. FCS-Pg supplementation at high dosage restored the gut microbiota composition with higher abundance of Alistipes and Bacteroidetes and lower abundance of Colidextribacter, Bilophila and Firmicutes compared with HFD group. Moreover, FCS-Pg decreased the expression of proteins involved in triglyceride synthesis such as glycerol 3-phosphate dehydrogenase 1 (GPD1) and increased the expression of proteins involved in lipolysis and thermogenesis such as adipose triglyceride lipase (ATGL) and uncoupling protein 1 (UCP1) in the white adipose tissue (WAT) compared with HFD group. In conclusion, our study suggested that FCS-Pg significantly prevented obesity and improved WAT function in HFD-fed mice by regulating intestinal lipid metabolism and microflora composition.

Probiotic post feed restriction supplementation on realimentation performances, carcass characteristic, gut morphology and gut microbes of broiler chicken

Probiotic post feed restriction supplementation on realimentation performances, carcass characteristic, gut morphology and gut microbes of broiler chicken

Can early gut microbiota screening reduce the incidence of cognitive impairment? A Mendelian randomization study.

Background: Gastrointestinal symptoms are now detected early in the clinical course of many dementia patients, and studies of the microbiome-gut-brain axis have confirmed bidirectional interactions between the gut and the brain. However, the causal relationship between gut microbiota and cognitive impairment has not been fully established. Therefore, this study conducted a bidirectional Mendelian randomization study to elucidate the potential causal relationship of gut microbiota to cognitive impairment. Objective: Using Mendelian randomization to identify gut flora with a genetic causal effect on the development of cognitive impairment. Methods: This study utilized publicly available genome-wide association study summary data to perform MR analysis, with gut microbiota as the exposure and various cognitive function indicators as well as scores for Alzheimer's disease as outcomes. This study selected single nucleotide polymorphisms as instrumental variables based on p-values, F-statistics, and r2. Bidirectional Mendelian randomization was conducted using methods such as inverse variance weighted, MR-Egger, simple mode, and weighted mode to assess the causal relationship. Concurrently, this study carried out Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis to identify potential heterogeneity and horizontal pleiotropy. Results: This study identified a total of 31 gut microbes that have a causal relationship with cognitive impairment, which include 1 phylum, 4 classes, 3 orders, 2 families, and 21 genera. Conclusions: This study unveiled specific gut microbiota associated with cognitive impairment, offering new insights and approaches for the prevention and treatment of cognitive impairment through gut microbiota such as Bifidobacterium and Ruminococcus gnavus group.

Probiotics by Modulating Gut-Brain Axis Together With Brivaracetam Mitigate Seizure Progression, Behavioral Incongruities, and Prevented Neurodegeneration in Pentylenetetrazole-Kindled Mice.

The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications. In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non-treated animals. Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ-induced neuropsychiatric disturbances such as anxiety and depressive-like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network-driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3). Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti-seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug-resistant seizures.

Multifrequency-STD NMR unveils the first Michaelis complex of an intramolecular trans-sialidase from Ruminococcus gnavus

RgNanH is an intramolecular trans-sialidase expressed by the human gut symbiont Ruminococcus gnavus, to utilise intestinal sialylated mucin glycan epitopes. Its catalytic domain, belonging to glycoside hydrolase GH33 family, cleaves off terminal sialic acid residues from mucins, releasing 2,7-anhydro-Neu5Ac which is then used as metabolic substrate by R. gnavus to proliferate in the mucosal environment. RgNanH is one of the three intramolecular trans-sialidases (IT-sialidases) characterised to date, and the first from a gut commensal organism. Here, saturation transfer difference NMR (STD NMR) in combination with computational techniques (molecular docking and CORCEMA-ST) were used to elucidate the specificity, kinetics and relative affinity of RgNanH for sialoglycans and 2,7-anhydro-Neu5Ac. We propose the first 3D model for the Michaelis complex of an IT-sialidase. This confirms the sialic acid to be the main recognition element for the interaction in the enzymatic cleft and highlights the crucial role of Trp698 to make CH-π stacking with the galactose residue of the substrate 3′-sialyllactose. The same contact is shown not to be possible for 6′-sialyllactose, due to geometrical constrains of the α-2,6 linkage. Indeed 6′-sialyllactose is not a substrate, even though it is shown to bind to RgNanH by STD NMR. These findings corroborate the role of Trp698 for the α-2,3 specificity of trans-sialidases. In this structural study, the use of Differential Epitope Mapping STD NMR (DEEP-STD NMR) approach allowed the validation of the proposed 3D models in solution. These structural approaches are shown to be instrumental in shedding light on the molecular mechanisms underpinning enzymatic reactions in the absence of enzyme-substrate X-ray structures.

Environmental endocrine disrupting chemical-DEHP exposure-provoked biotoxicity about microbiota-gut-mammary axis in lactating mice via multi-omics technologies

Plastics, pervasive in humans and nature, often contain Di (2-ethylhexyl) phthalate (DEHP) that enhance plastic’s elasticity. However, DEHP is an environmental endocrine disruptor, affecting organisms upon exposure. Understanding mammary gland development in lactating females is crucial for offspring nourishment and dairy production. Employing multi-omics technology, this study aimed to uncover DEHP’s impact on the microbial–gut–mammary axis. Forty mice were exposed to varying DEHP doses for 18 d. We performed 16S sequencing, metabolomics, mammary tissue observation, and gene expression profiling. Results revealed DEHP’s influence on microbial diversity, with increased Lactobacillus abundance and reduced Proteobacteria, alongside colonic inflammation. Elevated GMP and adenosine 5′-monophosphate levels in the bloodstream were noted, while ascorbic acid, glycitein, and others decreased. MEHP, a DEHP metabolite, damaged mammary tissues, inhibiting ERK1/2 phosphorylation, triggering apoptosis and ferroptosis. These findings unveil potential therapeutic targets for DEHP-induced chronic toxicity in humans and animals, aiding dairy livestock health and human well-being. This study underscores the importance of understanding the adverse effects of DEHP exposure on mammalian systems.

The Role of Gut Microbioma in Human Health: Exploring the Impact on Metabolism, Immunity, and Neurological Disorders

Abstract: The human microbiota has been progressively accepted for its role in sustaining overall health and well-being. The gut microflora vigorously communicates with the host metabolic system that exert influence on the progression, maturation, immune cells development and immune homeostasis maintenance. For the proper functioning of the immune system a diversified and steady gut microflora is needed, while “Dysbiosis” or an imbalance in the gut microbioma will lead to autoimmune and inflammatory diseases. The gut microbiota provides shape to our immune response and contribute to host protection against pathogen or bacterium through mechanisms such as the transformation of pro- inflammatory cytokine production, regulatory T-cell inductor and by intestinal mucosaql barrier. In addition to gut microbiota can affect our neurological function and play a key role in the pathogenesis of psychological disorders such as autism, depression, anxiety, Parkinson and Alzheimer’s disease. Gut microbiota can regulate neurological disorders by supplementing them with fecal transplantation, probiotics and antibiotics. An important parameter to consider gut microbioma disorder is Firmicutes/ Bacteroidetes.

Influence of gender, age, and body mass index on the gut microbiota of individuals from South China.

The symbiotic gut microbiota is pivotal for human health, with its composition linked to various diseases and metabolic disorders. Despite its significance, there remains a gap in systematically evaluating how host phenotypes, such as gender, age, and body mass index (BMI), influence gut microbiota. We conducted an analysis of the gut microbiota of 185 Chinese adults based on whole-metagenome shotgun sequencing of fecal samples. Our investigation focused on assessing the effects of gender, age, and BMI on gut microbiota across three levels: diversity, gene/phylogenetic composition, and functional composition. Our findings suggest that these phenotypes have a minor impact on shaping the gut microbiome compared to enterotypes, they do not correlate significantly within- or between-sample diversity. We identified a substantial number of phenotype-associated genes and metagenomic linkage groups (MLGs), indicating variations in gut microflora composition. Specifically, we observed a decline in beneficial Firmicutes microbes, such as Eubacterium, Roseburia, Faecalibacterium and Ruminococcus spp., in both older individuals and those with higher BMI, while potentially harmful microbes like Erysipelotrichaceae, Subdoligranulum and Streptococcus spp. increased with age. Additionally, Blautia and Dorea spp. were found to increase with BMI, aligning with prior research. Surprisingly, individuals who were older or overweight exhibited a lack of Bacteroidetes, a dominant phylum in the human gut microbiota that includes opportunistic pathogens, while certain species of the well-known probiotics Bifidobacterium were enriched in these groups, suggesting a complex interplay of these bacteria warranting further investigation. Regarding gender, several gender-associated MLGs from Bacteroides, Parabacteroides, Clostridium and Akkermansia were enriched in females. Functional analysis revealed a multitude of phenotype-associated KEGG orthologs (KOs). Our study underscores the influence of gender, age, and BMI on gut metagenomes, affecting both phylogenetic and functional composition. However, further investigation is needed to elucidate the precise roles of these bacteria, including both pathogens and probiotics.

Development of a Limosilactobacillus reuteri therapeutic delivery platform with reduced colonization potential.

Bacterial biotherapeutic delivery vehicles have the potential to treat a variety of diseases. This approach obviates the need to purify the recombinant effector molecule, allows delivery of therapeutics in situ via oral or intranasal administration, and protects the effector molecule during gastrointestinal transit. Lactic acid bacteria have been broadly developed as therapeutic delivery vehicles though risks associated with the colonization of a genetically modified microorganism have so-far not been addressed. Here, we present an engineered Limosilactobacillus reuteri strain with reduced colonization potential. We applied a dual-recombineering scheme for efficient barcoding and generated mutants in genes encoding five previously characterized and four uncharacterized putative adhesins. Compared with the wild type, none of the mutants were reduced in their ability to survive gastrointestinal transit in mice. CmbA was identified as a key protein in L. reuteri adhesion to HT-29 and enteroid cells. The nonuple mutant, a single strain with all nine genes encoding adhesins inactivated, had reduced capacity to adhere to enteroid monolayers. The nonuple mutant producing murine IFN-β was equally effective as its wild-type counterpart in mitigating radiation toxicity in mice. Thus, this work established a novel therapeutic delivery platform that lays a foundation for its application in other microbial therapeutic delivery candidates and furthers the progress of the L. reuteri delivery system towards human use.IMPORTANCEOne major advantage to leverage gut microbes that have co-evolved with the vertebrate host is that evolution already has taken care of the difficult task to optimize survival within a complex ecosystem. The availability of the ecological niche will support colonization. However, long-term colonization of a recombinant microbe may not be desirable. Therefore, strategies need to be developed to overcome this potential safety concern. In this work, we developed a single strain in which we inactivated the encoding sortase, and eight genes encoding characterized/putative adhesins. Each individual mutant was characterized for growth and adhesion to epithelial cells. On enteroid cells, the nonuple mutant has a reduced adhesion potential compared with the wild-type strain. In a model of total-body irradiation, the nonuple strain engineered to release murine interferon-β performed comparable to a derivative of the wild-type strain that releases interferon-β. This work is an important step toward the application of recombinant L. reuteri in humans.

GutMGene v2.0: an updated comprehensive database for target genes of gut microbes and microbial metabolites.

The gut microbiota is essential for various physiological functions in the host, primarily through the metabolites it produces. To support researchers in uncovering how gut microbiota contributes to host homeostasis, we launched the gutMGene database in 2022. In this updated version, we conducted an extensive review of previous papers and incorporated new papers to extract associations among gut microbes, their metabolites, and host genes, carefully classifying these as causal or correlational. Additionally, we performed metabolic reconstructions for representative gut microbial genomes from both human and mouse. gutMGene v2.0 features an upgraded web interface, providing users with improved accessibility and functionality. This upgraded version is freely available at http://bio-computing.hrbmu.edu.cn/gutmgene. We believe that this new version will greatly advance research in the gut microbiota field by offering a comprehensive resource.

Gut heavy metal and antibiotic resistome of humans living in the high Arctic.

Contaminants, such as heavy metals (HMs), accumulate in the Arctic environment and the food web. The diet of the Indigenous Peoples of North Greenland includes locally sourced foods that are central to their nutritional, cultural, and societal health but these foods also contain high concentrations of heavy metals. While bacteria play an essential role in the metabolism of xenobiotics, there are limited studies on the impact of heavy metals on the human gut microbiome, and it is so far unknown if and how Arctic environmental contaminants impact the gut microbes of humans living in and off the Arctic environment. Using a multiomics approach including amplicon, metagenome, and metatranscriptome sequencing, we identified and assembled a near-complete (NC) genome of a mercury-resistant bacterial strain from the human gut microbiome, which expressed genes known to reduce mercury toxicity. At the overall ecological level studied through α- and β-diversity, there was no significant effect of heavy metals on the gut microbiota. Through the assembly of a high number of NC metagenome-assembled genomes (MAGs) of human gut microbes, we observed an almost complete overlap between heavy metal-resistant strains and antibiotic-resistant strains in which resistance genes were all located on the same genetic elements.