Host-microbiota Interactions Research Articles

Fecal let-7b and miR-21 directly modulate the intestinal microbiota, driving chronic inflammation

ABSTRACT Inflammatory bowel diseases (IBD) etiology is multifactorial. Luminal microRNAs (miRNAs) have been suspected to play a role in the promotion of chronic inflammation, but the extent to which fecal miRNAs are interacting with the intestinal ecosystem in a way that contribute to diseases, including IBD, remains unknown. Here, fecal let-7b and miR-21 were found elevated, associated with inflammation, and correlating with multiple bacteria in IBD patients and IL-10–/– mice, model of spontaneous colitis. Using an in vitro microbiota modeling system, we revealed that these two miRNAs can directly modify the composition and function of complex human microbiota, increasing their proinflammatory potential. In vivo investigations revealed that luminal increase of let-7b drastically alters the intestinal microbiota and enhances macrophages’ associated proinflammatory cytokines (TNF, IL-6, and IL-1β). Such proinflammatory effects are resilient and dependent on the bacterial presence. Moreover, we identified that besides impairing the intestinal barrier function, miR-21 increases myeloperoxidase and antimicrobial peptides secretion, causing intestinal dysbiosis. More importantly, in vivo inhibition of let-7b and miR-21 with anti-miRNAs significantly improved the intestinal mucosal barrier function and promoted a healthier host-microbiota interaction in the intestinal lining, which altogether conferred protection against colitis. In summary, we provide evidence of the functional significance of fecal miRNAs in host-microbiota communication, highlighting their therapeutic potential in intestinal inflammation and dysbiosis-related conditions, such as IBD.

Associations of Neonatal Dairy Calf Faecal Microbiota with Inflammatory Markers and Future Performance.

After birth, the immune system is challenged by numerous elements of the extrauterine environment, reflected in fluctuations of inflammatory markers. The concentrations of these markers in the first month of life are associated with the future performance of dairy youngstock. It is thought that bacterial genera colonizing the calf intestinal tract can cause inflammation and thus affect their host's performance via immunomodulation. This study explored how the faecal microbiota of newborn dairy calves were related to inflammatory markers during the first three weeks of life, and if the abundance of specific genera was associated with first-lactation performance. Ninety-five female Holstein calves were studied. Once a week, serum and faecal samples were collected, serum concentrations of serum amyloid A, haptoglobin, tumour necrosis factor-α, and interleukin-6 were measured, and faecal microbiota composition was examined by 16S rRNA gene amplicon sequencing. Faecal Gallibacterium abundance in the first week of age and Collinsella abundance in the second week were negatively associated with inflammatory response as well as with calving-conception interval. Peptostreptococcus abundance in the second week of life was positively associated with inflammatory response and calving-conception interval, and negatively with average daily weight gain. In the third week, Dorea abundance was positively, Bilophila abundance was negatively associated with inflammatory response, and both genera were negatively associated with age at first calving. These bacterial genera may be able to influence the inflammatory response and through this, possibly the future performance of the dairy heifer. Deciphering such microbiota-host interactions can help improve calf management to benefit production and welfare.

Spaceflight alters host-gut microbiota interactions

The ISS rodent habitat has provided crucial insights into the impact of spaceflight on mammals, inducing symptoms characteristic of liver disease, insulin resistance, osteopenia, and myopathy. Although these physiological responses can involve the microbiome on Earth, host-microbiota interactions during spaceflight are still being elucidated. We explore murine gut microbiota and host gene expression in the colon and liver after 29 and 56 days of spaceflight using multiomics. Metagenomics revealed significant changes in 44 microbiome species, including relative reductions in bile acid and butyrate metabolising bacteria like Extibacter muris and Dysosmobacter welbionis. Functional prediction indicate over-representation of fatty acid and bile acid metabolism, extracellular matrix interactions, and antibiotic resistance genes. Host gene expression described corresponding changes to bile acid and energy metabolism, and immune suppression. These changes imply that interactions at the host-gut microbiome interface contribute to spaceflight pathology and that these interactions might critically influence human health and long-duration spaceflight feasibility.

Temporal Dynamics of Copper-Based Nanopesticide Transfer and Subsequent Modulation of the Interplay Between Host and Microbiota Across Trophic Levels.

During agricultural production, significant quantities of copper-based nanopesticides (CBNPs) may be released into terrestrial ecosystems through foliar spraying, thereby posing a potential risk of biological transmission via food chains. Consequently, we investigated the trophic transfer of two commonly available commercial CBNPs, Reap2000 (RP) and HolyCu (HC), in a plant-caterpillar terrestrial food chain and evaluated impacts on host microbiota. Upon foliar exposure (with 4 rounds of spraying, totaling 6.0 mg CBNPs per plant), leaf Cu accumulation levels were 726 ± 180 and 571 ± 121 mg kg-1 for RP and HC, respectively. HC exhibited less penetration through the cuticle compared to RP (RP: 55.5%; HC: 32.8%), possibly due to size exclusion limitations. While caterpillars accumulated higher amounts of RP, HC exhibited a slightly higher trophic transfer factor (TTF; RP: 0.69 ± 0.20; HC: 0.74 ± 0.17, p > 0.05) and was more likely to be transferred through the food chain. The application of RP promoted the dispersal of phyllosphere microbes and perturbed the original host intestinal microbiota, whereas the HC group was largely host-modulated (control: 65%; RP: 94%; HC: 34%). Integrating multiomics analyses and modeling approaches, we elucidated two pathways by which plants exert bottom-up control over caterpillar health. Beyond the direct transmission of phyllosphere microbes, the leaf microbiome recruited upon exposure to CBNPs further influenced the ingestion behavior and intestinal microbiota of caterpillars via altered leaf metabolites. Elevated Proteobacteria abundance benefited caterpillar growth with RP, while the reduction of Proteobacteria with HC increased the risk of lipid metabolism issues and gut disease. The recruited Bacteroidota in the RP phyllosphere proliferated more extensively into the caterpillar gut to enhance stress resistance. Overall, the gut microbes reshaped in RP caterpillars exerted a strong regulatory effect on host health. These findings expand our understanding of the dynamic transmission of host-microbiota interactions with foliar CBNPs exposure, and provide critical insight necessary to ensure the safety and sustainability of nanoenabled agricultural strategies.

Microbiota-Derived Extracellular Vesicle as Emerging Actors in Host Interactions.

The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota-host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions.

A host of issues: pseudoreplication in host-microbiota studies.

Pseudoreplication compromises the validity of research by treating non-independent samples as independent replicates. This review examines the prevalence of pseudoreplication in host-microbiota studies, highlighting the critical need for rigorous experimental design and appropriate statistical analysis. We systematically reviewed 115 manuscripts on host-microbiota interactions. Our analysis revealed that 22% of the papers contained pseudoreplication, primarily due to co-housed organisms, whereas 52% lacked sufficient methodological details. The remaining 26% adequately addressed pseudoreplication through proper experimental design or statistical analysis. The high incidence of pseudoreplication and insufficient information underscores the importance of methodological reporting and statistical rigor to ensure reproducibility of host-microbiota research.

Association of breast milk-derived arachidonic acid-induced infant gut dysbiosis with the onset of atopic dermatitis

ObjectiveThe specific breast milk-derived metabolites that mediate host–microbiota interactions and contribute to the onset of atopic dermatitis (AD) remain unknown and require further investigation.DesignWe enrolled 250 mother–infant pairs and collected...

Multiomics of parkinsonism cynomolgus monkeys highlights significance of metabolites in interaction between host and microbiota

The gut microbiota has been demonstrated to play a significant role in the pathogenesis of Parkinson’s disease (PD). However, conflicting findings regarding specific microbial species have been reported, possibly due to confounding factors within human populations. Herein, our current study investigated the interaction between the gut microbiota and host in a non-human primate (NHP) PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) using a multi-omic approach and a self-controlled design. Our transcriptomic sequencing of peripheral blood leukocytes (PBL) identified key genes involved in pro-inflammatory cytokine dysregulation, mitochondrial function regulation, neuroprotection activation, and neurogenesis associated with PD, such as IL1B, ATP1A3, and SLC5A3. The metabolomic profiles in serum and feces consistently exhibited significant alterations, particularly those closely associated with inflammation, mitochondrial dysfunctions and neurodegeneration in PD, such as TUDCA, ethylmalonic acid, and L-homophenylalanine. Furthermore, fecal metagenome analysis revealed gut dysbiosis associated with PD, characterized by a significant decrease in alpha diversity and altered commensals, particularly species such as Streptococcus, Butyrivibrio, and Clostridium. Additionally, significant correlations were observed between PD-associated microbes and metabolites, such as sphingomyelin and phospholipids. Importantly, PDPC significantly reduced in both PD monkey feces and serum, exhibiting strong correlation with PD-associated genes and microbes, such as SLC5A3 and Butyrivibrio species. Moreover, such multi-omic differential biomarkers were linked to the clinical rating scales of PD monkeys. Our findings provided novel insights into understanding the potential role of key metabolites in the host-microbiota interaction involved in PD pathogenesis.

Involvement of the gut microbiota in the metabolic phenotypes of two sympatric gerbils

Temporal niche partitioning is a crucial strategy for sympatric species to avoid predation and competition for habitat space and food resources. This study investigated the effect of the gut microbiota on the metabolic rhythms of two sympatric gerbil species (Meriones unguiculatus and Meriones meridianus) to test the hypothesis that the oscillatory patterns of microbiota may not fully mirror those of the host's metabolism. Experiment 1 compared the circadian metabolic and gut microbiota rhythms of M. unguiculatus (n = 12) and M. meridianus (n = 12) and measured the subjects' body temperatures and environmental temperature preferences. In Experiment 2.1, six M. meridianus gerbils were treated with antibiotics, and in Experiment 2.2, 21 M. unguiculatus gerbils (seven per treatment) were randomly gavaged with saline or a gut microbiota suspension from either M. unguiculatus or M. meridianus; their metabolic rhythms were subsequently measured. The results showed that the two gerbils had different metabolic phenotypes that determined activity heterogeneity and contributed to their coexistence. The relative abundances of Bacteroidetes, Actinobacteria, and Cyanobacteria in M. meridianus varied rhythmically in parallel with the daily metabolic rate, which was significantly higher at night than during the day. The rhythm of the metabolic rate was not noticeable in M. unguiculatus. However, in M.unguiculatus, the relative abundances of Firmicutes, Bacteroidetes, Proteobacteria, and Verrucomicrobia were significantly higher during the day than at night, while Cyanobacteria exhibited the opposite pattern. Antibiotic treatment significantly weakened the metabolic rhythms of M. meridianus, and the circadian rhythms slowly recovered after stopping antibiotic gavage. However, after transplanting M. meridianus' gut microbiota into M. unguiculatus, the metabolic rate of M. unguiculatus was not significantly different from that of the control groups. Our hypothesis was partly supported: the microbiota was only partially involved in regulating the metabolic rhythms of gerbils, and other factors could compensate for the effect of the gut microbiota on host metabolic rhythms. This finding underscores the complexity of host–microbiota interactions and highlights the need for further exploration into the multifaceted mechanisms governing host metabolic regulation.

E-Cigarette Use, Cigarette Smoking, and Sex are Associated with Nasal Microbiome Dysbiosis.

Previous research suggests that e-cigarettes can alter immune function, including in the nasal mucosa, in unique ways. The respiratory microbiome plays a key role in respiratory host defense, but the effects of e-cigarettes on the respiratory or nasal microbiome, are not well understood. Using 16S rRNA gene sequencing on nasal samples from adult e-cigarette users, smokers, and nonsmokers, we determined that e-cigarette use and cigarette smoking are associated with differential respiratory microbiome dysbiosis and substantial sex-dependent differences in the nasal microbiome, particularly in e-cigarette users. Staphylococcus aureus, a common respiratory pathogen, was more abundant in both e-cigarette users and smokers in comparison with nonsmokers, while Lactobacillus iners, often consider a protective species, was more abundant in smokers but less abundant in e-cigarette users in comparison with nonsmokers. In addition, we identified significant dysbiosis of the nasal microbiome between e-cigarette users and smokers with high versus low serum cotinine levels, an indicator of tobacco product use and toxicant exposure. We also analyzed nasal lavage fluid for immune mediators associated with host-microbiota interactions. Our analysis identified disruption of immune mediators in the nose of e-cigarette users and smokers, which is indicative of disrupted respiratory mucosal immune responses. Taken together, our data identified unique, sex-dependent host immune dysfunction associated with e-cigarette use in the nasal mucosa. More broadly, our data highlight the need for continued inclusion and careful consideration of sex as an important variable in the context of toxicant exposures. This is the first study investigating the effects of e-cigarette use and sex on the nasal microbiome, which is considered an important gatekeeper for protecting the lower respiratory tract from pathogens. We found significant sex, exposure group, and serum cotinine level associated differences in the composition of the nasal microbiome, demonstrating the importance of considering sex in future nasal microbiome studies and warranting further investigation of the mechanisms by which e-cigarette use dysregulates nasal immune homeostasis.

Toll-like receptor 13-mediated signaling protects against the development of colon cancer.

Appropriate host-microbiota interactions are essential for maintaining intestinal homeostasis; hence, an imbalance in these interactions leads to inflammation-associated intestinal diseases. Toll-like receptors (TLRs) recognize microbial ligands and play a key role in host-microbe interactions in health and disease. TLR13 has a well-established function in enhancing host defenses against pathogenic bacteria. However, its role in maintaining intestinal homeostasis and controlling colitis-associated colon cancer (CAC) is largely unknown. This study aimed to investigate the involvement of TLR13-mediated signaling in intestinal homeostasis and colonic tumorigenesis using ex vivo cell and in vivo CAC animal model. Tlr13-deficient mice were prone to dextran sodium sulfate (DSS)-induced colitis. During the early stages of the CAC regimen (AOM/DSS-treated), Tlr13 deficiency led to severe ulcerative colitis. Moreover, Tlr13-deficient mice exhibited increased intestinal permeability, as evidenced by elevated levels of fluorescein isothiocyanate (FITC)-dextran, endotoxins, and bacterial translocation. Enhanced cell survival and proliferation of colonic intestinal cells were observed in Tlr13-deficient mice. A transcriptome analysis revealed that Tlr13 deficiency is associated with substantial changes in gene expression profile of colonic tumor tissue. Tlr13-deficient mice were more susceptible to CAC, with increased production of interleukin (IL)-6, IL-12, and TNF-α cytokines and enhanced STAT3, NF-κB, and MAPK signaling in colon tissues. These findings suggest that TLR13 plays a protective role in maintaining intestinal homeostasis and controlling CAC. Our study provides a novel perspective on intestinal health via TLR13-mediated signaling, which is crucial for deciphering the role of host-microbiota interactions in health and disease.

Understanding the Conundrum of Pancreatic Cancer in the Omics Sciences Era.

Pancreatic cancer (PC) is an increasing cause of cancer-related death, with a dismal prognosis caused by its aggressive biology, the lack of clinical symptoms in the early phases of the disease, and the inefficacy of treatments. PC is characterized by a complex tumor microenvironment. The interaction of its cellular components plays a crucial role in tumor development and progression, contributing to the alteration of metabolism and cellular hyperproliferation, as well as to metastatic evolution and abnormal tumor-associated immunity. Furthermore, in response to intrinsic oncogenic alterations and the influence of the tumor microenvironment, cancer cells undergo a complex oncogene-directed metabolic reprogramming that includes changes in glucose utilization, lipid and amino acid metabolism, redox balance, and activation of recycling and scavenging pathways. The advent of omics sciences is revolutionizing the comprehension of the pathogenetic conundrum of pancreatic carcinogenesis. In particular, metabolomics and genomics has led to a more precise classification of PC into subtypes that show different biological behaviors and responses to treatments. The identification of molecular targets through the pharmacogenomic approach may help to personalize treatments. Novel specific biomarkers have been discovered using proteomics and metabolomics analyses. Radiomics allows for an earlier diagnosis through the computational analysis of imaging. However, the complexity, high expertise required, and costs of the omics approach are the main limitations for its use in clinical practice at present. In addition, the studies of extracellular vesicles (EVs), the use of organoids, the understanding of host-microbiota interactions, and more recently the advent of artificial intelligence are helping to make further steps towards precision and personalized medicine. This present review summarizes the main evidence for the application of omics sciences to the study of PC and the identification of future perspectives.

Ribonuclease 4 functions as an intestinal antimicrobial protein to maintain gut microbiota and metabolite homeostasis

Antimicrobial proteins contribute to host-microbiota interactions and are associated with inflammatory bowel disease (IBD), but our understanding on antimicrobial protein diversity and functions remains incomplete. Ribonuclease 4 (Rnase4) is a potential antimicrobial protein with no known function in the intestines. Here we find that RNASE4 is expressed in intestinal epithelial cells (IEC) including Paneth and goblet cells, and is detectable in human and mouse stool. Results from Rnase4-deficient mice and recombinant protein suggest that Rnase4 kills Parasutterella to modulate intestinal microbiome, thereby enhancing indoleamine-2,3-dioxygenase 1 (IDO1) expression and subsequently kynurenic and xanthurenic acid production in IECs to reduce colitis susceptibility. Furthermore, deceased RNASE4 levels are observed in the intestinal tissues and stool from patients with IBD, correlating with increased stool Parasutterella. Our results thus implicate Rnase4 as an intestinal antimicrobial protein regulating gut microbiota and metabolite homeostasis, and as a potential diagnostic biomarker and therapeutic target for IBD.

Strategies for the development of metalloimmunotherapies.

Metal ions play crucial roles in the regulation of immune pathways. In fact, metallodrugs have a long record of accomplishment as effective treatments for a wide range of diseases. Here we argue that the modulation of interactions of metal ions with molecules and cells involved in the immune system forms the basis of a new class of immunotherapies. By examining how metal ions modulate the innate and adaptive immune systems, as well as host-microbiota interactions, we discuss strategies for the development of such metalloimmunotherapies for the treatment of cancer and other immune-related diseases.

Common dietary emulsifiers promote metabolic disorders and intestinal microbiota dysbiosis in mice

Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota–host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus–bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

Bisphenol S exposure induces intestinal inflammation via altering gut microbiome

Bisphenol S (BPS), a substitute for bisphenol A, is widely used in the manufacture of food packaging materials, raising concern over its toxicity. However, evidence is still lacking on whether gut microbiota involved in BPS induced intestinal inflammation in mammals, as well as its underlying mechanism. Using mouse BPS exposure model, we found intestinal inflammation characterized by shortened colon length, crypt distortion, macrophage accumulation and increased apoptosis. As for gut microbiota, 16s rRNA gene amplicon sequencing showed BPS exposure induced gut dysbiosis, including increased pro-inflammatory microbes such as Ileibacterium, and decreased anti-inflammatory genera such as Lactobacillus, Blautia and Romboutsia. Besides, LC-MS/MS-based untargeted metabolomic analysis indicated BPS impaired both bacteria and host metabolism. Additionally, transcriptome analysis of the intestine revealed abnormal gene expression in intestinal mucosal barrier and inflammation. More importantly, treating mice with antibiotics significantly attenuated BPS-induced gut inflammation via the regulation of both bacterial and host metabolites, indicating the role of gut microbiota. Collectively, BPS exposure induces intestinal inflammation via altering gut microbiota in mouse. This study provides the possibility of madecassic acid, an anti-inflammatory metabolite, to prevent BPS-induced intestinal inflammation and also new insights in understanding host-microbiota interaction in BPS toxicity.

Evidence of size-dependent toxicity of polystyrene nano- and microplastics in sea cucumber Apostichopus japonicus (Selenka, 1867) during the intestinal regeneration

Microplastics are ubiquitous pollutants in the global marine environment. However, few studies have adequately explored the different toxic mechanisms of microplastics (MPs) and nanoplastics (NPs) in aquatic organisms. The sea cucumber, Apostichopus japonicus, is a key organism in the marine benthic ecosystem due to its crucial roles in biogeochemical cycles and food web. This study investigated the bioaccumulation and adverse effects of polystyrene micro- and nanoplastics (PS-M/NPs) of different sizes (20 μm, 1 μm and 80 nm) in the regenerated intestine of A. japonicus using multi-omics analysis. The results showed that after 30-day exposure at the concentration of 0.1 mg L−1, PS-MPs and PS-NPs accumulated to 155.41–175.04 μg g−1 and 337.95 μg g−1, respectively. This excessive accumulation led to increased levels of antioxidases (SOD, CAT, GPx and T-AOC) and reduced activities of immune enzymes (AKP, ACP and T-NOS), indicating oxidative damage and compromised immunity in the regenerated intestine. PS-NPs had more profound negative impacts on cell proliferation and differentiation compared to PS-MPs. Transcriptomic analysis revealed that PS-NPs primarily affected pathways related to cellular components, e.g., ribosome, and oxidative phosphorylation. In comparison, PS-MPs had greater influences on actin-related organization and organic compound metabolism. In the PS-M/NPs-treated groups, differentially expressed metabolites were mainly amino acids, fatty acids, glycerol phospholipid, and purine nucleosides. Additionally, microbial community reconstruction in the regenerated intestine was severely disrupted by the presence of PS-M/NPs. In the PS-NPs group, Burkholderiaceae abundance significantly increased while Rhodobacteraceae abundance decreased. Correlation analyses demonstrated that intestinal regeneration of A. japonicus was closely linked to its enteric microorganisms. These microbiota-host interactions were notably affected by different PS-M/NPs, with PS-NPs exposure causing the most remarkable disruption of mutual symbiosis. The multi-omic approaches used here provide novel insights into the size-dependent toxicity of PS-M/NPs and highlight their detrimental effects on invertebrates in M/NPs-polluted marine benthic ecosystems.

INTESTINAL DYSBIOSIS AND ACNE

Introduction: The balance between intestinal microbiota and skin is essential for health, including acne prevention and understanding these interactions is role for developing targeted acne therapies. Objective: This literature review aims to elucidate the interconnection between the intestinal microbiome and health, focusing on the etiology and intensity of acne, and examining modifications in intestinal microbiota and their effect on acne pathogenesis. Results and discussion: Intestinal dysbiosis, Western diet, Cutibacterium acnes, and microbiota-host interactions are key elements in acne pathogenesis, affecting sebum production and triggering inflammatory responses. The diet, especially the Western one, influences both intestinal microbiota and acne, highlighting the relationship between gastrointestinal and skin health. C. acnes plays a essential role in acne by stimulating sebum production and triggering inflammatory responses in the skin. Conclusion: Intestinal microbiome, skin microbiota, diet, dysbiosis, and C. acnes are key research areas for understanding and treating acne, emphasizing the importance of diet in skin health. Dietary interventions may benefit acne patients, leading to more effective and personalized therapeutic approaches.

Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure

Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.

A mechanistic modelling approach of the host-microbiota interactions to investigate beneficial symbiotic resilience in the human gut.

The health and well-being of a host are deeply influenced by the interactions with its gut microbiota. Contrasted environmental conditions, such as diseases or dietary habits, play a pivotal role in modulating these interactions, impacting microbiota composition and functionality. Such conditions can also lead to transitions from beneficial to detrimental symbiosis, viewed as alternative stable states of the host-microbiota dialogue. This article introduces a novel mathematical model exploring host-microbiota interactions, integrating dynamics of the colonic epithelial crypt, microbial metabolic functions, inflammation sensitivity and colon flows in a transverse section. The model considers metabolic shifts in epithelial cells based on butyrate and hydrogen sulfide concentrations, innate immune pattern recognition receptor activation, microbial oxygen tolerance and the impact of antimicrobial peptides on the microbiota. Using the model, we demonstrated that a high-protein, low-fibre diet exacerbates detrimental interactions and compromises beneficial symbiotic resilience, underscoring a destabilizing effect towards an unhealthy state. Moreover, the proposed model provides essential insights into oxygen levels, fibre and protein breakdown, and basic mechanisms of innate immunity in the colon and offers a crucial understanding of factors influencing the colon environment.