Host-microbe Interactions Research Articles

Gut microbiota-mediated hsa_circ_0126925 targets BCAA metabolic enzyme BCAT2 to exacerbate colorectal cancer progression.

Recent evidence indicates that a high-fat diet (HFD) can promote tumor development, especially colorectal cancer (CRC), by influencing the microbiota. Regulatory circular RNAs (circRNAs) play an important role in modulating host-microbe interactions; however, the specific mechanisms by which circRNAs influence cancer progression by regulating these interactions remain unclear. Here, we report that consumption of a HFD modulates the microbiota by specifically upregulating the expression of the noncoding RNA hsa_circ_0126925 (herein referred to as circ_0126925) in CRC. Acting as a scaffold, circ_0126925 hinders the recruitment of the E3 ubiquitin ligase tripartite motif-containing protein 21 (TRIM21) to branched-chain amino acid transaminase 2 (BCAT2), leading to reduced degradation of BCAT2. This reduction in targeted degradation of BCAT2 can protect tumours from limited branched-chain amino acids (BCAAs) interference by improving the metabolism of BCAAs in CRC. Taken together, these data demonstrate that circ_0126925 plays a critical role in promoting the progression of CRC by maintaining BCAA metabolism and provide insight into the functions and crosstalk of circ_0126925 in host-microbe interactions in CRC. Implications: This study preliminarily confirms that circRNAs do indeed respond to microbiota/microbial metabolites, providing further evidence for the potential development of circRNAs as diagnostic tools and/or therapeutic agents to alleviate microbiome related pathology in humans.

Investigating the Translational Value of Periprosthetic Joint Infection Models to Determine the Risk and Severity of Staphylococcal Biofilms.

With the advent of antibiotic-eluting polymeric materials for targeting recalcitrant infections, using preclinical models to study biofilms are crucial for improving the treatment efficacy in periprosthetic joint infections. The stratification of risk and severity of infections is needed to develop an effective clinical dosing framework with better treatment outcomes. We use in vivo and in vitro implant-associated infection models to demonstrate that methicillin-sensitive and resistant Staphylococcus aureus (MSSA and MRSA) have model-dependent distinct implant and peri-implant tissue colonization patterns. The maturity of biofilms and the location (implant vs tissue) were found to influence the antibiotic susceptibility evolution profiles of MSSA and MRSA, and the models could capture the differing host-microbe interactions in vivo. Gene expression studies revealed the molecular heterogeneity of colonizing bacterial populations. The comparison and stratification of the risk and severity of infection across different preclinical models provided in this study can guide clinical dosing to prevent or treat PJI effectively.

326 Modulation of microbe-host interaction in rosacea during topical ivermectin treatment

326 Modulation of microbe-host interaction in rosacea during topical ivermectin treatment

A Diazeniumdiolate Signal in Pseudomonas syringae Upregulates Virulence Factors and Promotes Survival in Plants.

Pseudomonas syringae infects a wide variety of crops. The mangotoxin-generating operon (mgo) is conserved across many P. syringae strains and is responsible for producing an extracellular chemical signal, leudiazen. Disruption of the mgoA gene in P. syringae pv. syringae (Pss) UMAF0158 alleviated tomato chlorosis caused by this bacterium. We showed that deletion of the entire mgo reduced Pss UMAF0158 population in tomato leaflets. Leudiazen restored the signaling activity of the deletion mutant at a concentration as low as 10 nM. Both the diazeniumdiolate and isobutyl groups of leudiazen are critical for this potent signaling activity. Transcriptional analysis showed that mgo and leudiazen induce the expression of mangotoxin biosynthetic operon as well as an uncharacterized gene cluster, RS17235-RS17245. We found that this cluster enhances the survival of Pss UMAF0158 in planta and is widely distributed in P. syringae strains. Our results demonstrate that mgo plays prominent roles in the virulence and growth of P. syringae. The mgo and mgo-like signaling systems in different bacteria likely regulate diverse microbe-host interactions. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

A Review on Microengineering of Epithelial Barriers for Biomedical and Pharmaceutical Research.

Epithelial tissue forms a barrier around the human body and visceral organs, providing protection, permeation, sensation, and secretion. It is vital for our sustenance as it protects the tissue from harm and injury by restricting the entry of foreign bodies inside. Furthermore, it is a strong barrier to drugs, nutrients, and other essential deliverables. This layer also houses a large consortium of microbes, which thrive in tandem with human tissue, providing several health benefits. Moreover, the complex interplay of the microbiome with the barrier tissue is poorly understood. Therefore, replicating these barrier tissues on microdevices to generate physiological and pathophysiological models has been a huge interest for researchers over the last few decades. The artificially engineered reconstruction of these epithelial cellular barriers on microdevices could help underpin the host-microbe interaction, generating a physiological understanding of the tissue, tissue remodeling, receptor-based selective diffusion, drug testing, and others. In addition, these devices could reduce the burden of animal sacrifices for similar research and minimize the failure rate in drug discovery due to the use of primary human cells and others. This review discusses the nature of the epithelial barrier at different tissue sites, the recent developments in creating engineered barrier models, and their applications in pathophysiology, host-microbe interactions, drug discovery, and cytotoxicity. The review aims to provide know-how and knowledge behind engineered epithelial barrier tissue to bioengineers, biotechnologists, and scientists in allied fields.

MicroRNA399s and strigolactones mediate systemic phosphate signaling between dodder‐connected host plants and control association of host plants with rhizosphere microbes

Summary A dodder (Cuscuta) often simultaneously parasitizes two or more adjacent hosts. Phosphate (Pi) deficiency is a common stress for plants, and plants often interact with soil microbes, including arbuscular mycorrhizal fungi (AMF), to cope with Pi stress. Little is known about whether dodder transmits Pi deficiency‐induced systemic signals between different hosts. In this study, dodder‐connected plant clusters, each composed of two tobacco (Nicotiana tabacum) plants connected by a dodder, were established, and in each cluster, one of the two tobacco plants was treated with Pi starvation. AMF colonization efficiency, rhizosphere bacterial community, and transcriptome were analyzed in the other dodder‐connected Pi‐replete tobacco plant to study the functions of interplant Pi signals. We found that dodder transfers Pi starvation‐induced systemic signals between host plants, resulting in enhanced AMF colonization, changes of rhizosphere bacterial communities, and alteration of transcriptomes in the roots of Pi‐replete plants. Importantly, genetic analyses indicated that microRNA399s (miR399s) and strigolactones suppress the systemic Pi signals and negatively affect AMF colonization in the Pi‐replete plants. These findings provide new insight into the ecological role of dodder in mediating host–host and host–microbe interactions and highlight the importance of strigolactone and miR399 pathways in systemic Pi signaling.

Gut Microbiota and Tryptophan Metabolism in Pathogenesis of Ischemic Stroke: A Potential Role for Food Homologous Plants

ScopeThe intestinal flora is involved in the maintenance of human health and the development of diseases, and is closely related to the brain. As an essential amino acid, tryptophan (TRP) participates in a variety of physiological functions in the body and affects the growth and health of the human body. TRP catabolites produced by the gut microbiota are important signaling molecules for microbial communities and host–microbe interactions, and play an important role in maintaining health and disease pathogenesis.Methods and resultsThe review first demonstrates the evidence of TRP metabolism in stroke and the relationship between gut microbiota and TRP metabolism. Furthermore, the review reveals that food homologous plants (FHP) bioactive compounds have been shown to regulate various metabolic pathways of the gut microbiota, including the biosynthesis of valine, leucine, isoleucine, and vitamin B6 metabolism. The most notable metabolic alteration is in TRP metabolism.ConclusionThe interaction between gut microbiota and TRP metabolism offers a plausible explanation for the notable bioactivities of FHP in the treatment of ischemic stroke (IS). This review enhances the comprehension of the underlying mechanisms associated with the bioactivity of FHP on IS.

The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice.

Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by inborn errors of cytotoxicity. Patients with biallelic PRF1 null mutations (encoding perforin) usually develop excessive immune cell activation, hypercytokinemia, and life-threateningimmunopathology in the first 6 months of life, often without an apparent infectious trigger. In contrast, perforin-deficient (PKO) mice only develop HLH after systemic infection with lymphocytic choriomeningitis virus (LCMV). We hypothesized that restricted microbe-immune cell interactions due to specific pathogen-free (SPF) housing might explain the need for this specific viral trigger in PKO mice. To investigate the influence of a "wild" microbiome in PKO mice, we fostered PKO newborns with Wildling microbiota ('PKO-Wildlings') and monitored them for signs of HLH. PKO-Wildlings survived long-term without spontaneous disease. Also, systemic infection with vaccinia virus did not reach the threshold of immune activation required to trigger HLH in PKO-Wildlings. Interestingly, after infection with LCMV, PKO-Wildlings developed an altered HLH pattern. This included lower IFN-γ serum levels along with improved IFN-γ-driven anemia, but more elevated levels of IL-17 and increased liver inflammation compared with PKO-SPF mice. Thus, wild microbiota alone is not sufficient to trigger HLH in PKO mice, but host-microbe interactions shape inflammatory cytokine patterns, thereby influencing manifestations of HLH immunopathology.

Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway: a potential therapeutic approach for neurodegenerative diseases.

The interaction between the gut microbiota and cyclic adenosine monophosphate (cAMP)- protein kinase A (PKA) signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut-brain axis. The gut microbiota influences the cAMP-PKA signaling pathway through its metabolites, which activates the vagus nerve and modulates the immune and neuroendocrine systems. Conversely, alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota, creating a dynamic network of microbial-host interactions. This reciprocal regulation affects neurodevelopment, neurotransmitter control, and behavioral traits, thus playing a role in the modulation of neurological diseases. The coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation, mitochondrial dysfunction, abnormal energy metabolism, microglial activation, oxidative stress, and neurotransmitter release, which collectively influence the onset and progression of neurological diseases. This study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway, along with its implications for potential therapeutic interventions in neurological diseases. Recent pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional disorders. This can be achieved through various methods such as dietary modifications, probiotic supplements, Chinese herbal extracts, combinations of Chinese herbs, and innovative dosage forms. These findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

An integrated microbiome- and metabolome-genome-wide association study reveals the role of heritable ruminal microbial carbohydrate metabolism in lactation performance in Holstein dairy cows

BackgroundDespite the growing number of studies investigating the connection between host genetics and the rumen microbiota, there remains a dearth of systematic research exploring the composition, function, and metabolic traits of highly heritable rumen microbiota influenced by host genetics. Furthermore, the impact of these highly heritable subsets on lactation performance in cows remains unknown. To address this gap, we collected and analyzed whole-genome resequencing data, rumen metagenomes, rumen metabolomes and short-chain fatty acids (SCFAs) content, and lactation performance phenotypes from a cohort of 304 dairy cows.ResultsThe results indicated that the proportions of highly heritable subsets (h2 ≥ 0.2) of the rumen microbial composition (55%), function (39% KEGG and 28% CAZy), and metabolites (18%) decreased sequentially. Moreover, the highly heritable microbes can increase energy-corrected milk (ECM) production by reducing the rumen acetate/propionate ratio, according to the structural equation model (SEM) analysis (CFI = 0.898). Furthermore, the highly heritable enzymes involved in the SCFA synthesis metabolic pathway can promote the synthesis of propionate and inhibit the acetate synthesis. Next, the same significant SNP variants were used to integrate information from genome-wide association studies (GWASs), microbiome-GWASs, metabolome-GWASs, and microbiome-wide association studies (mWASs). The identified single nucleotide polymorphisms (SNPs) of rs43470227 and rs43472732 on SLC30A9 (Zn2+ transport) (P < 0.05/nSNPs) can affect the abundance of rumen microbes such as Prevotella_sp., Prevotella_sp._E15-22, Prevotella_sp._E13-27, which have the oligosaccharide-degradation enzymes genes, including the GH10, GH13, GH43, GH95, and GH115 families. The identified SNPs of chr25:11,177 on 5s_rRNA (small ribosomal RNA) (P < 0.05/nSNPs) were linked to ECM, the abundance alteration of Pseudobutyrivibrio_sp. (a genus that was also showed to be linked to the ECM production via the mWASs analysis), GH24 (lysozyme), and 9,10,13-TriHOME (linoleic acid metabolism). Moreover, ECM, and the abundances of Pseudobutyrivibrio sp., GH24, and 9,10,13-TRIHOME were significantly greater in the GG genotype than in the AG genotype at chr25:11,177 (P < 0.05). By further the SEM analysis, GH24 was positively correlated with Pseudobutyrivibrio sp., which was positively correlated with 9,10,13-triHOME and subsequently positively correlated with ECM (CFI = 0.942).ConclusionOur comprehensive study revealed the distinct heritability patterns of rumen microbial composition, function, and metabolism. Additionally, we shed light on the influence of host SNP variants on the rumen microbes with carbohydrate metabolism and their subsequent effects on lactation performance. Collectively, these findings offer compelling evidence for the host-microbe interactions, wherein cows actively modulate their rumen microbiota through SNP variants to regulate their own lactation performance.C1VA69ck9huqCRa2wNrTKWVideo

Stability in fecal metabolites amid a diverse gut microbiome composition: a one-month longitudinal study of variability in healthy individuals

ABSTRACT An extensive network of microbial-host interactions exists in the gut, making the gut microbiome a complex ecosystem to untangle. The microbial composition and the fecal metabolites are important readouts to investigate intricate microbiota-diet-host interplay. However, this ecosystem is dynamic, and it is of interest to understand the degree and timescale of changes occurring in the gut microbiota, during disease as well as in healthy individuals. Cross-sectional study design is often used to investigate the microbiome, but this design provides a static snapshot and cannot provide evidence on the dynamic nature of the gut microbiome. Longitudinal studies are better suited to extrapolate causation in a study or assess changes over time. This study investigates longitudinal change in the gut microbiome and fecal metabolites in 14 healthy individuals with weekly sampling over a period of one-month (four time points), to elucidate the temporal changes occurring in the gut microbiome composition and fecal metabolites. Utilizing 16S rRNA amplicon sequencing for microbiome analysis and NMR spectroscopy for fecal metabolite characterization, we assessed the stability of these two types of measurable parameters in fecal samples during the period of one month. Our results show that the gut microbiome display large variations between healthy individuals, but relatively lower within-individual variations, which makes it possible to uniquely identify individuals. The fecal metabolites showed higher stability over time compared to the microbiome and exhibited consistently smaller variations both within and between individuals. This relative higher stability of the fecal metabolites suggests a balanced, consistent output even amid individual’s differences in microbial composition and they can provide a viable complementary readout to better understand the microbiome activity.

Emergence of dauer larvae in Caenorhabditis elegans disrupts continuity of host-microbiome interactions.

Nematodes are common in most terrestrial environments, where populations are often known to undergo cycles of boom and bust. Useful in such scenarios, nematodes present developmental programs of diapause, giving rise to stress-resistant larvae and enabling dispersal in search of new resources. Best studied in Caenorhabditis elegans, stress resistant dauer larvae emerge under adverse conditions, primarily starvation, and migrate to new niches where they can resume development and reproduce. C. elegans is a bacterivore but has been shown to harbor a persistent and characteristic gut microbiome. While much is known about the gut microbiome of reproducing C. elegans, what dauers harbor is yet unknown. This is of interest, as dauers are those that would enable transmission of microbes between nematode generations and geographical sites, maintaining continuity of host-microbe interactions. Using culture-dependent as well as sequencing-based approaches we examined the gut microbiomes of dauers emerging following population growth on ten different natural-like microbially diverse environments as well as on two defined communities of known gut commensals and found that dauers were largely devoid of gut bacteria. These results suggest that host gut-microbiome interactions in C. elegans are not continuous across successive generations and may reduce the likelihood of long-term worm-microbe coevolution.

Bacteroides uniformis ameliorates pro-inflammatory diet-exacerbated colitis by targeting endoplasmic reticulum stress-mediated ferroptosis

IntroductionA pro-inflammatory diet is positively associated with the risk and progression of inflammatory bowel diseases (IBD). Recently, ferroptosis has been observed in patients with different dietary patterns-associated intestinal inflammation, while the mechanisms underlying the effects of a pro-inflammatory diet and whether it mediates ferroptosis are unknown. ObjectivesThis study aims to elucidate the mechanisms underlying pro-inflammatory diet-mediated colitis and explore potential intervention strategies. MethodsMice were fed a dietary inflammatory index-based pro-inflammatory diet for 12 weeks. Subsequently, colitis was chemically induced using 2.5 % dextran sulfate sodium. The body weight, pathological score, immune response and mucosal barrier function were evaluated to assess intestinal inflammation. Intestine tissue transcriptomics, fecal microbiome analysis and serum metabolomics were applied to identify diet–microbe–host interactions. Additionally, the dietary inflammatory index (DII) scores and intestinal specimens of 32 patients with Crohn’s disease were evaluated. The biological functions of Bacteroides uniformis were observed in vitro and in vivo. ResultsPro-inflammatory diet induces low-grade intestinal inflammation in mice and exacerbates colitis by activating glutathione peroxidase 4-associated ferroptosis in the endoplasmic reticulum stress-mediated pathway. These effects are reversed by ferrostatin-1 treatment. Additionally, the pro-inflammatory diet triggers colitis by modulating the gut microbiota and metabolites. Notably, supplementation with B. uniformis improves the pro-inflammatory diet-aggravated colitis by inhibiting endoplasmic reticulum stress-mediated ferroptosis. Moreover, B. uniformis is non-enterotoxigenic and non-enteroinvasive in co-cultures with intestinal epithelial cells. ConclusionsPro-inflammatory diet drives colitis by targeting endoplasmic reticulum stress-mediated ferroptosis, possibly in a gut microbiota-dependent manner. Pro-inflammatory diet restriction and microbial-based therapies may be effective strategies for preventing and treating IBD.

Undernutrition disrupts jejunal and ileal microbiota and epithelial tissue homeostasis in a pregnant sheep model

Nutrition consistently affects microbe-host interactions in the gastrointestinal tract. This study aimed to unravel how undernutrition reshapes the microbial composition and the homeostasis of epithelium in the jejunum and ileum. Sixteen late-gestation Hu-sheep were randomly assigned to the control group (n = 8, 100% ad libitum feeding levels) or the undernutrition group (n = 8, which received 30% ad libitum feeding levels). After 15-d treatment, all ewes were slaughtered, and jejunal and ileal digesta and epithelium samples were collected for 16S rRNA gene sequencing and transcriptome sequencing, respectively. Results indicated that undernutrition decreased the jejunal and ileal tissue weights (P = 0.005 and P = 0.022) and the levels of volatile fatty acids (P = 0.019 and P = 0.007) and microbial protein levels (P = 0.019 and P = 0.031) in jejunal and ileal digesta. The relative abundance of acetate producing microbiota, including Clostridia UCG-014 norank, Ruminococcus, [Ruminococcus] gauvreauii, and Lachnospiraceae_Blautia, were significantly reduced (P < 0.05) in the jejunum and ileum. Undernutrition up-regulated (P < 0.05) the expression of genes involved in amino acid synthesis and fatty acid oxidation, but down-regulated (P < 0.05) the expression of genes associated with amino acid degradation, fatty acid synthesis, and extracellular structures in jejunal and ileal epithelium. In the jejunal epithelium, genes associated with extracellular matrix-receptor interactions, cell growth, and immune response were down-regulated (P < 0.05) upon undernutrition. Taken together, undernutrition changed the microbial community in the jejunum and ileum, which altered the fermentation mode and the production of volatile fatty acids and microbial protein. These affected the energy and protein system in the epithelium and reprogrammed substance metabolism and extracellular structures, which probably further influenced cell growth and immune response. These insights provide a foundation for completely clarifying the crosstalk between small intestinal microbiota and the host.

Early-life Upper Airway Microbiota are Associated with Decreased Lower Respiratory Tract Infections

Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. To gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics, we sequenced and analyzed nasal (n=229) and oral (n=210) microbiomes with associated health/environmental data from our Wisconsin Infant Study Cohort at age 24-months. Participants with early-life lower respiratory tract infection (LRTI) were more likely to be formula-fed, attend daycare, and experience wheezing. Shotgun metagenomic sequencing with detection of viral and bacterial respiratory pathogens revealed nasal microbiome composition to associate with prior LRTI – namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M. catarrhalis, suggesting interbacterial competition impacts nasal pathogen colonization. This work advances understanding of protective host-microbial interactions occurring in airway microbiomes that alter infection susceptibility in early-life.

Wheat straw and alfalfa hay alone or combined in a high-concentrate diet alters microbial-host interaction in the rumen of lambs

The inclusion of various forages in a normal forage-to-concentrate ratio has widely been reported to reveal the changes that occur in the foregut tissues. However, the mechanism by which the wheat straw, alfalfa hay, or both alter the orchestrated crosstalk of microbiome and host-transcriptome in the rumen of lambs fed a high-concentrate diet is elusive. Sixty-three Hulunbuir lambs were randomly allotted to 3 dietary groups, and each dietary group had 3 pens with 7 lambs. The lambs were fed high-concentrate diets (70%) supplemented with either 30% wheat straw (30S), a mixture of 15% alfalfa hay and 15% wheat straw (30M), or 30% alfalfa hay (30A) over a 2-week adaptation period and a 12-week formal trial. Compared with the 30S and 30A groups, the 30M group had greater (P < 0.05) levels of plasma glucagon-like peptide (GLP-2), interleukin-2 (IL-2). Humoral immunity showed a tendency to increase in the 30M group, as evidenced by the greater levels of plasma immunoglobulins (Ig) A and IgG (P > 0.05). The 16S rRNA result showed that the abundance of Lachnospiraceae (NK3A20 group and unclassified), Olsenella, Shuttleworthia, and Succiniclasticum were enriched in the 30M group. Meanwhile, the abundances of Ruminococcaceae NK4A214 and prevetolla_7 were enriched in 30S and 30A, respectively. The RNA-seq identified 35 shared differentially expressed genes (DEGs) between the “30S vs. 30M” and “30S vs. 30A,” enriched in lipid metabolism pathways, including glycerophospholipid and arachidonic acid metabolism. The weighted gene co-expression network analysis results revealed that the expression of genes in the darkred (194 genes) and darkgreen (134 genes) modules showed a strong positive correlation with phenotypic traits and bacterial genera, respectively. The genes in the darkgreen module were involved in carbohydrate, lipid, and amino acid metabolism and showed a wide range of associations with Prevotella_7, Shuttleworthia, and Succiniclasticum, indicating that ruminal microbes might act as a vital driver in the microbiome-host interaction, likely through fermentation of end-products or metabolites. In conclusion, the results indicate that microbiome enrichment in response to feeding wheat straw and alfalfa hay might drive microbiome-host crosstalk to regulate rumen function in lambs fed a high-concentrate diet.

Segatella clades adopt distinct roles within a single individual’s gut

Segatella is a prevalent genus within individuals’ gut microbiomes worldwide, especially in non-Western populations. Although metagenomic assembly and genome isolation have shed light on its genetic diversity, the lack of available isolates from this genus has resulted in a limited understanding of how members’ genetic diversity translates into phenotypic diversity. Within the confines of a single gut microbiome, we have isolated 63 strains from diverse lineages of Segatella. We performed comparative analyses that exposed differences in cellular morphologies, preferences in polysaccharide utilization, yield of short-chain fatty acids, and antibiotic resistance across isolates. We further show that exposure to Segatella isolates either evokes strong or muted transcriptional responses in human intestinal epithelial cells. Our study exposes large phenotypic differences within related Segatella isolates, extending this to host-microbe interactions.

Gut microbiota: a crucial player in the combat against tuberculosis.

The mammalian gastrointestinal tract quickly becomes densely populated with foreign microorganisms shortly after birth, thereby establishing a lifelong presence of a microbial community. These commensal gut microbiota serve various functions, such as providing nutrients, processing ingested compounds, maintaining gut homeostasis, and shaping the intestinal structure in the host. Dysbiosis, which is characterized by an imbalance in the microbial community, is closely linked to numerous human ailments and has recently emerged as a key factor in health prognosis. Tuberculosis (TB), a highly contagious and potentially fatal disease, presents a pressing need for improved methods of prevention, diagnosis, and treatment strategies. Thus, we aim to explore the latest developments on how the host's immune defenses, inflammatory responses, metabolic pathways, and nutritional status collectively impact the host's susceptibility to or resilience against Mycobacterium tuberculosis infection. The review addresses how the fluctuations in the gut microbiota not only affect the equilibrium of these physiological processes but also indirectly influence the host's capacity to resist M. tuberculosis. This work highlights the central role of the gut microbiota in the host-microbe interactions and provides novel insights for the advancement of preventative and therapeutic approaches against tuberculosis.

Trace antibiotic exposure affects murine gut microbiota and metabolism

Gut microbiota is important for host metabolism regulation. Antibiotic exposure disturbs this regulation by affecting the microbiome. Trace levels of antibiotics in water have been widely reported and the impact on gut microbiota remains understudied. We provide evidence of trace antibiotic exposure affecting the host's gut microbiota using a mouse model exposed to trace amounts of azithromycin (AZI) or ciprofloxacin (CIP) in drinking water. AZI exposure in males changed the distribution of gram-positive (Firmicutes and Bacteroidetes) and gram-negative (Proteobacteria, Fusobacteria, and Verrucomicrobia) bacteria at an early age. Both AZI and CIP resulted in abnormal microbiota maturation. Additionally, the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and propionate, in females is affected. Serum hormone and metabolome levels shifted after trace antibiotic exposure. AZI and CIP exposure broadly disrupted original host-microbe interaction relationships between the gut microbiota and SCFAs or serum metabolites. In this study, we demonstrated that trace antibiotic exposure was associated with extensive gut microbiota and metabolism perturbation in mice and that the potential health risks in susceptible populations should be considered.

Microbial and Transcriptomic Landscape Associated With Neutrophil Extracellular Traps in Perianal Fistulizing Crohn's Disease.

Perianal fistulizing Crohn's disease (pfCD) poses significant healing challenges, closely associated with neutrophil extracellular traps (NETs). This study aimed to investigate the microbe-host interactions influencing NETs in pfCD. From January 2019 to July 2022, patients with pfCD were screened at Ren Ji Hospital. Patients in remission following comprehensive treatment were recruited. We documented clinical characteristics, medication regimens, healing outcomes, and infliximab levels in fistula tissues. NET positivity was confirmed by positive results in citrullinated histone H3 (CitH3) enzyme-linked immunosorbent assay (ELISA) and dual immunofluorescence staining for myeloperoxidase and CitH3. Microbial and transcriptomic profiles from fistula tissues, obtained during surgery, were analyzed using 16S rRNA gene sequencing and RNA sequencing. Differences in microbiome and transcriptomic profiles were evaluated, and their relationships were assessed using Mantel's and Spearman's coefficients. Significant differences in microbial communities were found between groups (P = .007). Representatively differential microbes such as Prevotella bivia, Streptococcus gordonii, and Bacteroides dorei were enriched in NETs-positive fistulas (P < .05). Functional analysis of microbes revealed reduced ubiquinol biosynthesis and butanoate production in NETs-negative fistulas (P < .05). Transcriptomic analysis indicated increased neutrophil and monocyte infiltration in NETs-positive fistulas, associated with pathways involving bacterial response, neutrophil chemotaxis, secretory processes, and peptidase activity (P < .05). Species prevalent in NETs-positive fistulas correlated positively with immune responses and wound healing pathways, whereas bacteria in NETs-negative fistulas correlated negatively. NETs were negatively associated with tissue infliximab levels (P = .001) and healing outcomes (P = .025). Our findings reveal unique microbial and transcriptomic signatures associated with NETs in pfCD, highlighting their profound influence on clinical outcomes.