Common Gut Research Articles

Salt-dependent Role of Human Gut Commensal Coprococcus comes in Blood Pressure and Inflammation

Introduction: We previously identified the effect of Coprococcus come, a common human gut microflora, on blood pressure regulation due to its metabolism of angiotensin-converting enzyme inhibitors (ACEi). Despite being reported as a butyrate-producer, there are no studies on C. comes in its direct role in hypertension and inflammation. Importantly, C. comes was enriched in the African American hypertensive population, almost three-fourths of whom were found salt sensitive. Therefore, we hypothesized that C. comes increased blood pressure and associated systemic inflammation in a salt-dependent manner. Methods: Once per day for 13 consecutive days, male Dahl salt-sensitive (S) rats (N=7-8/group) were administered 109 CFU of C. comes via oral gavage on both low and high salt diet. Systolic blood pressure, diastolic blood pressure, and mean arterial pressure were recorded on day 13 by radio-telemetry. On day 14, spleen (the key organ in systemic inflammation) and kidney (the key organ in salt hypertension) were collected for analyses of inflammatory markers by real time PCR and flow cytometry. Results: In low salt rats, the administration of C. comes did not significantly change blood pressures, but resulted in immunosuppression in the spleen, as evidenced by decreased inflammatory markers Il6 (0.79 fold, p<0.05) and Il17rc (0.74 fold, p<0.001). In contrast, there were significant increases in the S rats on high salt+ C. comes vs high salt in systolic blood pressure (183.2 vs 179.9 mmHg, p<0.01), diastolic blood pressure (130.5 vs 127.1 mmHg, p<0.01), and mean arterial pressures (156.7 vs 151.8 mmHg, p<0.0001) during nighttime, but not daytime. The administration of C. comes in high salt rats led to increased inflammation in the spleen, as measured by the percentage of CD11b/c+ cells (high salt+ C. comes 2.9% vs high salt 2.1% p<0.05) and CD68+ cells (high salt+ C. comes 0.28% vs high salt 0.22% p<0.05), as well as in the kidney, as measured by inflammatory markers Il1b (4.4 fold, p<0.05), Il17rc (8.8 fold, p<0.05), and Tnf (1.67 fold, p<0.05). Conclusion: C. comes, an ACEi degrader, suppressed splenic inflammation in the male S rats on a low salt diet without impacting blood pressure. However, on high salt diet, C. comes administration resulted in increased splenic and renal inflammation as well as increased blood pressure in the male S rats. These findings support the pathogenic role of C. comes in salt-induced hypertension, providing evidence for targeting C. comes in blood pressure control. This study is funded by NIH R21AG079357 and AHA CDA 852969. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Fates of Commensal Specific, Innate-like CD8 +T cells in the Gut

Abstract Barrier tissues such as the skin and gut are host to a variety of microbes collectively termed the microbiota. To maintain host homeostasis, sufficient exposure to the microbiota is necessary, however, diseases such as Inflammatory Bowel Disease (IBD), have been described as occurring amidst breakdown in the normal communication between host and microbe. Fundamentally, IBD is a disease of aberrant immune activation to the microbiota and epithelial barrier dysfunction. At the skin barrier, we have previously described the H2-M3 restricted, CD8 +T cell response in mice after topical exposure to a commensal microbe that aids in barrier maintenance and epithelial repair. However, the residence of these H2-M3 restricted, commensal specific T cells in the gut, and potential contribution to barrier function in this tissue is unknown. We have now identified H2-M3 restricted CD8 +T cells populating the lamina propria and intraepithelial compartments of both the colon and small intestine following novel commensal exposure. Further, during inflammatory conditions these cells drastically expand and produce pro-inflammatory Type 1 cytokines. Following these discoveries, we have developed novel tetramer reagents to track and interrogate the function of H2-M3 restricted T cell responses to Helicobacter hepaticus, a common gut commensal with known roles in perpetuating colitis in immunocompromised animals. Utilizing these tools, we hope to uncover how these non-classically restricted immune responses to the same commensal under homeostatic or inflammatory conditions differ, to identify potential targets to correct aberrant reactivity to the microbiota during colitis. NIH-Oxford Cambridge Scholars Program

Sunflower plantings reduce a common gut pathogen and increase queen production in common eastern bumblebee colonies.

Community diversity can reduce the prevalence and spread of disease, but certain species may play a disproportionate role in diluting or amplifying pathogens. Flowers act as both sources of nutrition and sites of pathogen transmission, but the effects of specific plant species in shaping bee disease dynamics are not well understood. We evaluated whether plantings of sunflower (Helianthus annuus), whose pollen reduces infection by some pathogens when fed to bees in captivity, lowered pathogen levels and increased reproduction in free-foraging bumblebee colonies (Bombus impatiens). Sunflower abundance reduced the prevalence of a common gut pathogen, Crithidia bombi, and reduced infection intensity, with an order of magnitude lower infection intensity at high sunflower sites compared with sites with little to no sunflower. Sunflower abundance was also positively associated with greater queen production in colonies. Sunflower did not affect prevalence of other detected pathogens. This work demonstrates that a single plant species can drive disease dynamics in foraging B. impatiens, and that sunflower plantings can be used as a tool for mitigating a prevalent pathogen while also increasing reproduction of an agriculturally important bee species.

Membrane Protein Amuc_1100 Derived from Akkermansia muciniphila Facilitates Lipolysis and Browning via Activating the AC3/PKA/HSL Pathway.

Obesity, defined as a disorder of lipid metabolism caused by white fat accumulation, is closely related to the gut microbiota. Akkermansia muciniphila (Akk), one of the most common gut commensals, can reduce fat storage and promote the browning of white adipocytes, alleviating disorders of lipid metabolism. However, which components of Akk produce the effect remain unclear, limiting the application of Akk in the treatment of obesity. Here, we found that the membrane protein Amuc_1100 of Akk decreased formation of lipid droplets and fat accumulation during the differentiation process and stimulated browning in vivo and in vitro. Transcriptomics revealed that Amuc_1100 accelerated lipolysis through upregulation of the AC3/PKA/HSL pathway in 3T3-L1 preadipocytes. Quantitative PCR (qPCR) and Western blotting showed that Amuc_1100 intervention promotes steatolysis and browning of preadipocytes by increasing lipolysis-related genes (AC3/PKA/HSL) and brown adipocyte marker genes (PPARγ, UCP1, and PGC1α) at both the mRNA and protein levels. These findings introduce new insight into the effects of beneficial bacteria and provide new avenues for the treatment of obesity. IMPORTANCE An important intestinal bacterial strain Akkermansia muciniphila contributes to improving carbohydrate and lipid metabolism, thus alleviating obesity symptoms. Here, we find that the Akk membrane protein Amuc_1100 regulates lipid metabolism in 3T3-L1 preadipocytes. Amuc_1100 inhibits lipid adipogenesis and accumulation during the differentiation process of preadipocytes, upregulates the browning-related genes of preadipocytes, and promotes thermogenesis through activation of uncoupling protein-1 (UCP-1), including Acox1 involved in lipid oxidation. Amuc_1100 accelerates lipolysis via the AC3/PKA/HSL pathway, phosphorylating HSL at Ser 660. The experiments illustrated here identify the specific molecules and functional mechanisms of Akk. Therapeutic approaches with Amuc_1100 derived from Akk may help alleviate obesity and metabolic disorders.

A New Fluorescent Probe Tool: ERNathG.

β-d-Glucuronidase (GUS) plays a pivotal role in both clinical treatment assessment and environmental monitoring. Existing tools for GUS detection suffer from (1) poor continuity due to a gap between the optimal pH of the probes and the enzyme and (2) diffusion from the detection site due to lack of an anchoring structure. Here we report a novel GUS pH-matching and endoplasmic reticulum-anchoring strategy for GUS recognition. The new fluorescent probe tool was termed ERNathG, which was designed and synthesized with β-d-glucuronic acid as the GUS-specific recognition site and 4-hydroxy-1,8-naphthalimide as a fluorescence reporting group, with a p-toluene sulfonyl as an anchoring group. This probe enabled the continuous and anchored detection of GUS without pH-adjustment for the related assessment of common cancer cell lines and gut bacteria. The probe's properties are far superior to those of commonly used commercial molecules.

No Evidence of a Genetic Causal Relationship between Ankylosing Spondylitis and Gut Microbiota: A Two-Sample Mendelian Randomization Study

Objective: Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of "parental alleles are randomly assigned to offspring" and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. Results: The random-effects IVW results showed that Bacteroides (p = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621-1.579]), Streptococcus (p = 0.591, OR 95% CI = 1.120 [0.741-1.692]), Proteobacteria (p = 0.522, OR 95% CI = 1.160 [0.737-1.826]), and Lachnospiraceae (p = 0.717, OR 95% CI = 1.073 [0.732-1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. Conclusions: This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation.

The Cyanobacterial "Nutraceutical" Phycocyanobilin Inhibits Cysteine Protease Legumain.

The blue biliprotein phycocyanin, produced by photo-autotrophic cyanobacteria including spirulina (Arthrospira) and marketed as a natural food supplement or "nutraceutical," is reported to have anti-inflammatory, antioxidant, immunomodulatory, and anticancer activity. These diverse biological activities have been specifically attributed to the phycocyanin chromophore, phycocyanobilin (PCB). However, the mechanism of action of PCB and the molecular targets responsible for the beneficial properties of PCB are not well understood. We have developed a procedure to rapidly cleave the PCB pigment from phycocyanin by ethanolysis and then characterized it as an electrophilic natural product that interacts covalently with thiol nucleophiles but lacks any appreciable cytotoxicity or antibacterial activity against common pathogens and gut microbes. We then designed alkyne-bearing PCB probes for use in chemical proteomics target deconvolution studies. Target identification and validation revealed the cysteine protease legumain (also known as asparaginyl endopeptidase, AEP) to be a target of PCB. Inhibition of this target may account for PCB's diverse reported biological activities.

Changes in the microbiota in different intestinal segments of mice with sepsis.

The small intestine, as the main digestion and absorption site of the gastrointestinal tract, is often overlooked in studies, and the overall microbiota does not reflect the makeup of the microbiota in different segments of the intestine. Therefore, we aimed to exclude the influence of routine ICU treatment measures on sepsis patients and observed changes in the diversity and abundance of gut microbiota in different intestinal segments of septic mice. The mice were randomly divided into the CLP6h group and the sham group. The contents of the colon and small intestine of the experimental group and the control group were collected after 6h. After CLP, the number and structure of the gut microbiota in the colon changed most obviously, among which Bacteroidetes had the most significant changes. Akkermansia, D.Firmicutes_bacterium_M10_2, Blautia, Bifidobacterium, Lactobacillus, Candidatus_Arthromitus, and Muribaculaceae were changed in the colon. Lactobacillus, Bifidobacterium, Akkermansia, Blautia, Candidatus_Arthromitus, and Lachnospiraceae_NK4A136_group were changed in the small intestine. Our experiment found that there were different numbers of unique and common gut microbiota in the small intestine and colon after sepsis, and the gut microbiota of the colon changed more drastically after sepsis than the small intestine. Thus, we should focus on protective gut microbiota and mucin-degrading microbes. We hope that these results will provide help for sepsis treatment in the future.

Treatment Resistance in Schizophrenia Is Associated with Attention Deficit/Hyperactivity Disorder and Gut Microbiota: A Genetic Correlation and Mendelian Randomization Study

Introduction: Observational studies highlight associations of common diseases with individual schizophrenia symptoms. However, it is unclear whether these diseases are associated with individual treatment-resistant schizophrenia (TRS). We aimed to explore the genetic associations between common immune diseases, metabolic diseases, psychiatric disorders, gut microbiota and TRS. Methods: Genome-wide association study (GWAS) summary data of European participants (n = ∼456,327) included TRS, 11 psychiatric disorders, 23 immune and metabolic diseases, body mass index, height, and 211 gut microbiota. In this genetic correlation and two-sample Mendelian randomization (MR) study, linkage disequilibrium score (LDSC) regression was applied to infer genetic correlation estimates. Two-sample MR tested potential causal associations of genetic variants associated with common immune diseases, metabolic diseases, psychiatric disorders, and gut microbiota with TRS. Results: LDSC revealed candidate associations between attention deficit/hyperactivity disorder (ADHD), schizophrenia, intestinal infectious diseases, obesity and TRS (genetic correlation range, 0.230–0.702; p < 0.05). Two-sample MR analyses suggested that ADHD was positively associated with TRS (estimate [SE] = 0.204 [0.073], p = 0.005), a finding that remained stable across statistical models. Besides, schizophrenia and genus Barnesiella levels were causally associated with TRS but not consistent across MR approaches. Conclusion: This study reports genetic correlations between ADHD, schizophrenia, intestinal infectious diseases, obesity and TRS. The study also found that genus Barnesiella was associated with TRS. These findings may have clinical implications, highlighting the possible strategy for TRS prevention.

Dietary Fish Meal Level and a Package of Choline, β-Glucan, and Nucleotides Modulate Gut Function, Microbiota, and Health in Atlantic Salmon (Salmo salar, L.).

Steatosis and inflammation have been common gut symptoms in Atlantic salmon fed plant rich diets. Choline has recently been identified as essential for salmon in seawater, and β-glucan and nucleotides are frequently used to prevent inflammation. The study is aimed at documenting whether increased fishmeal (FM) levels (8 levels from 0 to 40%) and supplementation (Suppl) with a mixture of choline (3.0 g/kg), β-glucan (0.5 g/kg), and nucleotides (0.5 g/kg) might reduce the symptoms. Salmon (186 g) were fed for 62 days in 16 saltwater tanks before samples were taken from 12 fish per tank for observation of biochemical, molecular, metabolome, and microbiome indicators of function and health. Steatosis but no inflammation was observed. Lipid digestibility increased and steatosis decreased with increasing FM levels and supplementation, seemingly related to choline level. Blood metabolites confirmed this picture. Genes in intestinal tissue affected by FM levels are mainly involved in metabolic and structural functions. Only a few are immune genes. The supplement reduced these FM effects. In gut digesta, increasing FM levels increased microbial richness and diversity, and changed the composition, but only for unsupplemented diets. An average choline requirement of 3.5 g/kg was indicated for Atlantic salmon at the present life stage and under the present condition.

Effect of Probiotsid-Phyto and UDP Zn on the intestinal microbiome of Cyprinus carpio

The system analysis of the phytobiotic “Probiocid®-Phyto” and zinc ultradispersed particles (Zn UDP) effect on growth dynamics, chemical composition of muscle tissue and structural microbiome of the common carp gut (Cyprinus carpio) was carried out in this article. The use of modern genetic methods of investigation (polymerase chain reaction with specific 16S prokaryotic primers and with Nextera XT protocol adapters and indices) allowed to determine that the main phylogenetic groups entering the intact group gut microbiome are Proteobacteria (40.49 %), Actinobacteria (28.67 %), Firmicutes (19.01 %) and Bacteroidetes (10.28 %). The most significant effect on the carp microbiome was exerted by Zn UDP, which was expressed by an increase in the specific weight of two types – Proteobacteria 66.64 % and Fusobacteria - 31.18 %, while in the bivalent application group the biodiversity of types was represented as follows: 57.08 % – Proteobacteria, 14.17 % – Firmicutes, 11.86 % – Actinobacteria, 7.85 % – Fusobacteria and 7.43 % – Bacteroidetes. The most significant effect of the preparations on the carp productivity was observed when the compared preparations were fed together; in this case, by the end of the experiment, the increase in carp live weight was 18.45 %. The research allows recommending the combined use of “Probiocid®- Phyto” (2 g/kg feed) and Zn UDP (10 mg/kg feed) as growth activators for common carp (Cyprinus carpio).

Effects of glycyrrhizin, stevioside, and sucralose on the growth and metabolism of the omnipresent gut commensal Escherichia coli

The rise in popularity of non-caloric sweeteners (NCS) among obese and diabetic patients is due to their ability to provide a sweet taste without any caloric input. However, NCS consumption may be linked to metabolic disorders. The mechanisms behind these adverse effects are still unclear, which suggests that NCS may alter the metabolic activity of the gut microbiome, leading to enteric environmental perturbation and resulting in physiological anomalies in the host. This study investigates how Escherichia coli, a common gut microbe, reacts to three NCS, two of which come from nature (glycyrrhizin and stevioside) and one that is made artificially (sucralose). To assess the impact of these NCS, this study investigated the growth, gene expression, and metabolic pathways of E. coli under different sweetener loads. Compared to the untreated control, low amounts of glycyrrhizin made E. coli grow faster, while similar amounts of sucralose and stevioside had no or a less noticeable effect. At higher concentrations, these sweeteners slowed down or inhibited the growth of the bacteria. Thus, NCS may have dose-dependent impacts on gut microbes. After treatment with amounts that corresponded to the acceptable daily intake, the expression of key metabolic genes showed altered expression, which may potentially affect their metabolism. At different concentrations of the NCS, there were clear differences in the global metabolomic profile between the control and the different NCS treatments. Under in vitro conditions, glycyrrhizin and sucralose appeared to have a less divergent impact on E. coli growth, gene expression, and metabolism, which may suggest that these are relatively safer sugar substitutes for humans.

Technical versus biological variability in a synthetic human gut community

ABSTRACT Synthetic communities grown in well-controlled conditions are an important tool to decipher the mechanisms driving community dynamics. However, replicate time series of synthetic human gut communities in chemostats are rare, and it is thus still an open question to what extent stochasticity impacts gut community dynamics. Here, we address this question with a synthetic human gut bacterial community using an automated fermentation system that allows for a larger number of biological replicates. We collected six biological replicates for a community initially consisting of five common gut bacterial species that fill different metabolic niches. After an initial 12 hours in batch mode, we switched to chemostat mode and observed the community to stabilize after 2–3 days. Community profiling with 16S rRNA resulted in high variability across replicate vessels and high technical variability, while the variability across replicates was significantly lower for flow cytometric data. Both techniques agree on the decrease in the abundance of Bacteroides thetaiotaomicron, accompanied by an initial increase in Blautia hydrogenotrophica. These changes occurred together with reproducible metabolic shifts, namely a fast depletion of glucose and trehalose concentration in batch followed by a decrease in formic acid and pyruvic acid concentrations within the first 12 hours after the switch to chemostat mode. In conclusion, the observed variability in the synthetic bacterial human gut community, as assessed with 16S rRNA gene sequencing, is largely due to technical variability. The low variability seen in HPLC and flow cytometry data suggests a highly deterministic system.

Gut microbe Lactiplantibacillus plantarum undergoes different evolutionary trajectories between insects and mammals

BackgroundAnimals form complex symbiotic associations with their gut microbes, whose evolution is determined by an intricate network of host and environmental factors. In many insects, such as Drosophila melanogaster, the microbiome is flexible, environmentally determined, and less diverse than in mammals. In contrast, mammals maintain complex multispecies consortia that are able to colonize and persist in the gastrointestinal tract. Understanding the evolutionary and ecological dynamics of gut microbes in different hosts is challenging. This requires disentangling the ecological factors of selection, determining the timescales over which evolution occurs, and elucidating the architecture of such evolutionary patterns.ResultsWe employ experimental evolution to track the pace of the evolution of a common gut commensal, Lactiplantibacillus plantarum, within invertebrate (Drosophila melanogaster) and vertebrate (Mus musculus) hosts and their respective diets. We show that in Drosophila, the nutritional environment dictates microbial evolution, while the host benefits L. plantarum growth only over short ecological timescales. By contrast, in a mammalian animal model, L. plantarum evolution results to be divergent between the host intestine and its diet, both phenotypically (i.e., host-evolved populations show higher adaptation to the host intestinal environment) and genomically. Here, both the emergence of hypermutators and the high persistence of mutated genes within the host’s environment strongly differed from the low variation observed in the host’s nutritional environment alone.ConclusionsOur results demonstrate that L. plantarum evolution diverges between insects and mammals. While the symbiosis between Drosophila and L. plantarum is mainly determined by the host diet, in mammals, the host and its intrinsic factors play a critical role in selection and influence both the phenotypic and genomic evolution of its gut microbes, as well as the outcome of their symbiosis.

Modulating the Gut Microbiota with Alginate Oligosaccharides In Vitro

Alginate oligosaccharides (AOS) are non-digestible carbohydrates from brown kelp. As such, they are dietary fibers and may have prebiotic potential. Therefore, we investigated the capacity of gut bacteria to utilize AOS with single-strain cultures and as a complex bacterial community. Bifidobacterium adolescentis, Lacticaseibacillus casei and Lacticaseibacillus paracasei showed weak growth (relative to unsupplemented medium; p &lt; 0.05) in the presence of AOS and alginate, while strong growth (p &lt; 0.01) was observed for Bacteroides ovatus when grown with alginate as carbohydrate source. Enterococcus faecium and Enterococcus hirae were for the first time reported to be able to grow on AOS. Further, AOS as substrate was investigated in a complex bacterial community with colonic fermentations in an in vitro gut model. The in vitro gut model indicated that AOS increased short-chain fatty acid (SCFA) levels in donors with a low endogenous SCFA production, but not to the same level as inulin. Bacteroides was found to dominate the bacteria community after in vitro gut simulation with alginate as substrate. Further, stimulation of Bacteroides was observed with AOS in the gut model for two out of three donors with the third donor being more resistant to change. Our results allowed the identification of AOS utilizers among common gut species. The results also demonstrated the capacity of AOS to elevate SCFA levels and positively modulate the gut microbiota during in vitro simulated colon fermentations, although some subjects appear to be resilient to perturbation via substrate changes.

Dietary lead modulates the mouse intestinal microbiome: Subacute exposure to lead acetate and lead contaminated soil

The effect of dietary lead on the intestinal microbiome has not been fully elucidated. To determine if there was an association between microflora modulation, predicted functional genes, and Pb exposure, mice were provided diets amended with increasing concentrations of a single lead compound, lead acetate, or a well characterized complex reference soil containing lead, i.e. 6.25–25 mg/kg Pb acetate (PbOAc) or 7.5–30 mg/kg Pb in reference soil SRM 2710a having 0.552 % Pb among other heavy metals such as Cd. Feces and ceca were collected following 9 days of treatment and the microbiome analyzed by 16 S rRNA gene sequencing. Treatment effects on the microbiome were observed in both feces and ceca of mice. Changes in the cecal microbiomes of mice fed Pb as Pb acetate or as a constituent in SRM 2710a were statistically different except for a few exceptions regardless of dietary source. This was accompanied by increased average abundance of functional genes associated with metal resistance, including those related to siderophore synthesis and arsenic and/or mercury detoxification. Akkermansia, a common gut bacterium, was the highest ranked species in control microbiomes whereas Lactobacillus ranked highest in treated mice. Firmicutes/Bacteroidetes ratios in the ceca of SRM 2710a treated mice increased more than with PbOAc, suggestive of changes in gut microbiome metabolism that promotes obesity. Predicted functional gene average abundance related to carbohydrate, lipid, and/or fatty acid biosynthesis and degradation were greater in the cecal microbiome of SRM 2710a treated mice. Bacilli/Clostridia increased in the ceca of PbOAc treated mice and may be indicative of increased risk of host sepsis. Family Deferribacteraceae also was modulated by PbOAc or SRM 2710a possibly impacting inflammatory response. Understanding the relationship between microbiome composition, predicted functional genes, and Pb concentration, especially in soil, may provide new insights into the utility of various remediation methodologies that minimize dysbiosis and modulate health effects, thus assisting in the selection of an optimal treatment for contaminated sites.

The antipsychotic drug olanzapine altered lipid metabolism in the common carp (Cyprinus carpio L.): Insight from the gut microbiota-SCFAs-liver axis

Olanzapine (OLA) is a common drug used to treat schizophrenia and has recently come under increasing scrutiny as an emerging contaminant. However, its impact on lipid metabolism in fish and its mechanisms of action are not well understood. In this study, common carp were exposed to 0, 10, 100, and 250 μM OLA for 60 days. The results indicated that OLA exposure increased weight gain, total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG) and decreased high-density lipoprotein (HDL). In addition, lipids accumulated in the liver of the common carp. To explore the underlying mechanisms of action, gut microbiota, short-chain fatty acids (SCFAs), liver transcripts, and genes related to lipid metabolism were measured. It was discovered that OLA exposure altered the common carp gut microbiota composition and increased the abundance of SCFA-producing bacteria. Correspondingly, this study showed that OLA exposure increased the levels of SCFAs, which are highly relevant to the development of lipid accumulation. Transcriptome sequencing results indicated that OLA exposure could change lipid metabolism signalling pathways, including steroid biosynthesis, the PPAR signalling pathway, asglycerophospholipid metabolism, glycerolipid metabolism, and fatty acid metabolic pathways of the common carp. Additionally, OLA exposure interrupted lipid metabolism by means of significant upregulation of lipid synthesis-related genes, including pparγ, srebp1, and fas. OLA exposure also resulted in significant lipolysis-related gene downregulation, including cpt, lpl, hsl, and pparα. The results of this study indicated that contamination of aquatic environments with OLA alters lipid metabolism in common carp. In addition, the underlying mechanism might be due in part to the modulation of the gut microbiota-SCFA-PPAR signalling pathway.

The multifaceted roles of common gut microbiota in immune checkpoint inhibitor-mediated colitis: From mechanism to clinical application.

With the arrival of the era of tumor immunotherapy, Immune Checkpoint Inhibitors have benefited countless tumor patients. However, the emergence of Immune-Related Adverse Events, especially Immune Checkpoint Inhibitor-Mediated Colitis (IMC), has become an important obstacle to immunotherapy. Therefore, it is very important to clarify the mechanism and influencing factors of IMC. The effect of gut microbiota on IMC is gradually becoming a research hotspot. Gut microbiota from different phyla can affect IMC by regulating innate and acquired immunity of tumor patients in various ways. In this review, we make a systematic and comprehensive introduction of the effect of gut microbiota on IMC. Through understanding the specific effects of gut microbiota on IMC, and then exploring the possibility of reducing IMC by regulating gut microbiota.

Infection by a eukaryotic gut parasite in wild Daphnia sp. associates with a distinct bacterial community.

Host-associated bacterial communities play an important role in host fitness and resistance to diseases. Yet, few studies have investigated tripartite interaction between a host, parasite and host-associated bacterial communities in natural settings. Here, we use 16S rRNA gene amplicon sequencing to compare gut- and body- bacterial communities of wild water fleas belonging to the Daphnia longispina complex, between uninfected hosts and those infected with the common and virulent eukaryotic gut parasite Caullerya mesnili (Family: Ichthyosporea). We report community-level changes in host-associated bacteria with the presence of the parasite infection; namely decreased alpha diversity and increased beta diversity at the site of infection, i.e. host gut (but not host body). We also report decreased abundance of bacterial taxa proposed elsewhere to be beneficial for the host, and an appearance of taxa specifically associated with infected hosts. Our study highlights the host-microbiota-infection link in a natural system and raises questions about the role of host-associated microbiota in natural disease epidemics as well as the functional roles of bacteria specifically associated with infected hosts.

Antimicrobial resistance-Do we share more than companionship with our dogs?

AimsTo investigate and compare antimicrobial resistance genes (ARGs) in faeces from cohabiting dogs and owners.Methods and ResultsDNA from faecal samples from 35 dogs and 35 owners was screened for the presence of 34 clinically relevant ARGs using high throughput qPCR. In total, 24 and 25 different ARGs were present in the dog and owner groups, respectively. The households had a mean of 9.9 ARGs present, with dogs and owners sharing on average 3.3 ARGs. ARGs were shared significantly more in households with dogs over 6 years old (3.5, interquartile range 2.75–5.0) than in households with younger dogs (2.5, interquartile range 2.0–3.0) (p = 0.02). Dogs possessed significantly more mecA and aminoglycoside resistance genes than owners.ConclusionsDogs and owners can act as reservoirs for a broad range of ARGs belonging to several antimicrobial resistance classes. A modest proportion of the same resistance genes were present in both dogs and owners simultaneously, indicating that ARG transmission between the dog and human gut is of minor concern in the absence of antimicrobial selection.Significance and Impact of the StudyThis study provides insight into the common dog and human gut resistomes, contributing to an improved knowledge base in risk assessments regarding ARG transmission between dogs and humans.