Human Microbiome Research Articles

Cultured fecal microbial community and its impact as fecal microbiota transplantation treatment in mice gut inflammation

The fecal microbiome is identical to the gut microbial communities and provides an easy access to the gut microbiome. Therefore, fecal microbial transplantation (FMT) strategies have been used to alter dysbiotic gut microbiomes with healthy fecal microbiota, successfully alleviating various metabolic disorders, such as obesity, type 2 diabetes, and inflammatory bowel disease (IBD). However, the success of FMT treatment is donor-dependent and variations in gut microbes cannot be avoided. This problem may be overcome by using a cultured fecal microbiome. In this study, a human fecal microbiome was cultured using five different media; growth in brain heart infusion (BHI) media resulted in the highest microbial community cell count. The microbiome (16S rRNA) data demonstrated that the cultured microbial communities were similar to that of the original fecal sample. Therefore, the BHI-cultured fecal microbiome was selected for cultured FMT (cFMT). Furthermore, a dextran sodium sulfate (DSS)-induced mice-IBD model was used to confirm the impact of cFMT. Results showed that cFMT effectively alleviated IBD-associated symptoms, including improved gut permeability, restoration of the inflamed gut epithelium, decreased expression of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-1, IL-6, IL-12, and IL-17), and increased expression of anti-inflammatory cytokines (IL-4 and IL-10). Thus, study’s findings suggest that cFMT can be a potential alternative to nFMT.Key points• In vitro fecal microbial communities were grown in a batch culture using five different media.• Fecal microbial transplantation was performed on DSS-treated mice using cultured and normal fecal microbes.• Cultured fecal microbes effectively alleviated IBD-associated symptoms.Graphical

Reconstruction characteristics of gut microbiota from patients with type 1 diabetes affect the phenotypic reproducibility of glucose metabolism in mice.

The human microbiota-associated (HMA) mice model, especially the germ-free (GF)-humanized mice, has been widely used to probe the causal relationships between gut microbiota and human diseases such as type 1 diabetes (T1D). However, most studies have not clarified the extent to which the reconstruction of the human donor microbiota in recipient mice correlates with corresponding phenotypic reproducibility. In this study, we transplanted fecal microbiota from five patients with T1D and four healthy people into GF mice, and microbiota from each donor were transplanted into 10 mice. Mice with similar microbiota structure to the donor exhibited better phenotypic reproducibility. The characteristics of the microbial community assembly of donors also influenced the phenotypic reproducibility in mice, and individuals with a higher proportion of stochastic processes showed more severe disorders. Microbes enriched in patients with T1D had a stronger colonization potential in mice with impaired glucose metabolism, and microbiota functional features related to T1D were better reproduced in these mice. This indicates that assembly traits and colonization efficacy of microbiota influence phenotypic reproducibility in GF-humanized mice. Our findings provide important insights for using HMA mice models to explore links between gut microbiota and human diseases.

Evaluating the potential prebiotic effects of umbu-cajá (Spondias spp.) fruit processing by-product flour on the human intestinal microbiota

This study evaluated the potential prebiotic properties of umbu-cajá (Spondias spp.) fruit processing by-product flour (UCF) on the human intestinal microbiota by monitoring the relative abundance of specific intestinal bacterial populations, microbial metabolic behavior, and antioxidant activity during 48 h of in vitro colonic fermentation using fecal inoculum donated from healthy adult individuals. UCF had a high insoluble fiber content and flavonols, especially quercetin-3-O-glucoside, as the most prevalent phenolic compounds, besides showing antioxidant activity. Medium with UCF increased the relative abundance of Lactobacillus spp./Enterococcus spp., Bifidobacterium spp., and Clostridium histolyticum during the colonic fermentation and decreased the relative abundance of Bacteroides spp./Prevotella spp. and Eubacterium rectale/Clostridium coccoides. Medium with UCF maintained a higher relative abundance of Ruminococcus albus/R. flavefaciens than negative control during the colonic fermentation. UCF stimulated intense metabolic activity of the intestinal microbiota during the colonic fermentation, evidenced by decreased pH values, sugar consumption, and production of several metabolites linked to host health promotion, concomitant with high antioxidant activity. The results characterize UCF as a candidate for prebiotic use and a novel value-added circular ingredient to functionalize foods and nutraceuticals.

The human microbiome in space: parallels between Earth-based dysbiosis, implications for long-duration spaceflight, and possible mitigation strategies.

SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats.

Analysis of genetic signatures of virulence and resistance in foodborne Staphylococcus aureus isolates from Algeria

Staphylococcus aureus, a frequent commensal of the human microbiota, also frequently associated with various infections. This study aimed to genetically characterize foodborne methicillin resistant S. aureus (MRSA) in Oran, Algeria. From a total of 474 food matrices, 30 MRSA strains were isolated and characterized using whole genome sequencing (WGS) and bioinformatics. The genomes were assessed for antimicrobial resistance and virulence genes, sequence and spa types and single nucleotide polymorphism (SNP) to establish their relationship. The prevalence of S. aureus was 34.38% with MRSA accounting for 18.40%. MRSA strains showed high resistance to penicillinG, ampicillin and tetracycline. However, inconsistencies were noted between phenotypic and genotypic resistance for methicillin, aminoglycosides, and phenicolates, with mecA gene identified in three isolates. The isolates revealed eight different sequence types (predominantly ST97 and ST45) and eleven spa types (mainly t230 and t8503), correlating with SNP clusters except for isolates belonging to ST7200.86.66% of isolates harboured at least one enterotoxin gene underscores their potential public health threat. This investigation highlights the genetic heterogeneity among S. aureus regarding virulence and antimicrobial resistance, shedding light into food safety in Algeria and the ease of using WGS approach to rapidly characterize bacterial pathogens in community environments.

Detection of Mycoplasma sp using next-generation DNA sequencing is common on nasal swabs from both healthy and unhealthy pet rabbits (Oryctolagus cuniculus).

Upper respiratory infections are a frequent problem in pet rabbits and rodents, and Mycoplasma pulmonis is 1 of the most common causes of respiratory infections in pet rats. M pulmonis was detected in 1967 in laboratory rabbits via culture of the nares and oropharynx, but overall, Mycoplasma is not commonly identified in the upper airway of rabbits. The objective of this study was to compare the prevalence of Mycoplasma sp detection via next-generation DNA sequencing on nasal swabs obtained from healthy and unhealthy rabbits. The results of nasal swabs from both healthy and unhealthy rabbits submitted for next-generation DNA sequencing from January 2022 to February 2023 were reviewed. Data gathered included signalment, whether or not Mycoplasma sp was detected, and the cell count and relative predominance of Mycoplasma sp compared to other organisms. 91 rabbits met the inclusion criteria, of which 49 were healthy and 42 were unhealthy. Overall, 52 of 91 (57.1%) rabbits were positive and 39 of 91 (42.8%) were negative for Mycoplasma sp. Mycoplasma positivity was significantly (P < .001) more common in healthy rabbits (37/49 [75.5%]) compared to unhealthy rabbits (15/42 [35.7%]). The fact that Mycoplasma positivity was common in both groups of rabbits, and particularly common in rabbits without upper respiratory signs, suggests that Mycoplasma may be normal nasal flora in rabbits. Further research is needed to determine whether Mycoplasma could function as an opportunistic pathogen in rabbits.

Simulated Gastrointestinal Digestion and Fecal Fermentation Characteristics of Exopolysaccharides Synthesized by Schleiferilactobacillus harbinensis Z171.

Exopolysaccharides (EPSs) produced by Lactobacillus have important physiological activities and are commonly used as novel prebiotics. A strain of Lactobacillus with high EPS yield was identified as Schleiferilactobacillus harbinensis (S. harbinensis Z171), which was isolated from Chinese sauerkraut. The objective of this study was to investigate the in vitro simulated digestion and fecal fermentation behavior of the purified exopolysaccharide fraction F-EPS1A from S. harbinensis Z171 and its influence on the human intestinal flora composition. The in vitro digestion results showed that the primary structural characteristics of F-EPS1A, such as morphology, molecular weight, and monosaccharide composition remained stable after saliva and gastrointestinal digestion. Compared with the blank group, the fermentation of F-SPS1A by fecal microbiota decreased the diversity of the bacterial communities, significantly promoted the relative abundance of Bifidobacterium and Faecalibacterium, and decreased the relative abundance of Lachnospiraceae_Clostridium, Fusobacterium, and Oscillospira. Reverse transcription polymerase chain reaction (RT-PCR) analysis also showed that the population of Bifidobacterium markedly increased. Furthermore, the total short-chain fatty acid levels increased significantly, especially for butyric acid. Gas chromatography-mass spectrometry (GC-MS) results showed that F-EPS1A could be fermented by the human gut microbiota to synthesize organic acids and derivative metabolites that are beneficial to gut health. Therefore, these findings suggest that F-EPS1A could be exploited as a potential prebiotic.

Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.

Alzheimer's disease (AD) is a neurodegenerative disorder with limited therapeutic options. Accordingly, new approaches for prevention and treatment are needed. One focus is the human microbiome, the consortium of microorganisms that live in and on us, which contributes to human immune, metabolic, and cognitive development and that may have mechanistic roles in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are recognized as spectrum disorders with complex pathobiology. AD/ADRD onset begins before overt clinical signs, but initiation triggers remain undefined. We posit that disruption of the normal gut microbiome in early life leads to a pathological cascade within septohippocampal and cortical brain circuits. We propose investigation to understand how early-life microbiota changes may lead to hallmark AD pathology in established AD/ADRD models. Specifically, we hypothesize that antibiotic exposure in early life leads to exacerbated AD-like disease endophenotypes that may be amenable to specific microbiological interventions. We propose suitable models for testing these hypotheses.

Causal roles of skin and gut microbiota in skin appendage disorders suggested by genetic study.

There is evidence from observational studies that human microbiota is linked to skin appendage Disorders (SADs). Nevertheless, the causal association between microbiota and SADs is yet to be fully clarified. A comprehensive two-sample Mendelian randomization (MR) was first performed to determine the causal effect of skin and gut microbiota on SADs. A total of 294 skin taxa and 211 gut taxa based on phylum, class, order, family, genus, and ASV level information were identified. Summary data of SADs and eight subtypes (acne vulgaris, hidradenitis suppurativa, alopecia areata, rogenic alopecia, rosacea, rhinophyma, seborrhoeic dermatitis, and pilonidal cyst) were obtained from the FinnGen consortium. We performed bidirectional MR to determine whether the skin and gut microbiota are causally associated with multiple SADs. Furthermore, sensitivity analysis was conducted to examine horizontal pleiotropy and heterogeneity. A total of 65 and 161 causal relationships between genetic liability in the skin and gut microbiota with SADs were identified, respectively. Among these, we separately found 5 and 11 strong causal associations that passed Bonferroni correction in the skin and gut microbiota with SADs. Several skin bacteria, such as Staphylococcus, Streptococcus, and Propionibacterium, were considered associated with multiple SADs. As gut probiotics, Bifidobacteria and Lactobacilli were associated with a protective effect on SAD risk. There was no significant heterogeneity in instrumental variables or horizontal pleiotropy. Our MR analysis unveiled bidirectional causal relationships between SADs and the gut and skin microbiota, and had the potential to offer novel perspectives on the mechanistic of microbiota-facilitated dermatosis.

Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.

Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection.

Native valve endocarditis caused by Corynebacterium striatum without underlying structural heart disease or indwelling cardiovascular medical devices: a case report

BackgroundCorynebacterium striatum (C. striatum) is a gram-positive, anaerobic bacillus found both environmentally and in human skin and nasal mucosa flora. It is reportedly the etiologic agent of community-acquired and nosocomial diseases and is significantly associated with bacteremia and medical endovascular devices. This is the rare case of mitral valve native valve endocarditis (NVE) caused by C. striatum occurring in a young adult without underlying structural heart disease or indwelling cardiovascular medical devices successfully treated with multidisciplinary therapy.Case presentationThe patient was a 28-year-old female with no medical history. She was transferred our hospital due to sudden onset of vertigo and vomit. A computed tomography on day 2 revealed the hydrocephalus due to the cerebellar infarction, and she underwent posterior fossa decompression for cerebellar infarction. An angiography on day 8 revealed a left vertebral artery dissection, which was suspected be the etiology. Afterwards, a sudden fever of 39 degrees developed on day 38. She was diagnosed with aspiration pneumonia and treated with ampicillin/sulbactam but was still febrile at the time of transfer for rehabilitation. Treatment continued with levofloxacin, the patient had no fever decline, and she was readmitted to our hospital. Readmission blood cultures (3/3 sets) revealed C. striatum, and an echocardiogram revealed an 11 mm long mitral valve vegetation, leading to NVE diagnosis. On the sixth illness day, cardiac failure symptoms manifested. Echocardiography revealed mitral valve rupture. She was transferred again on the 11th day of illness, during which time her mitral valve was replaced. C. striatum was detected in the vegetation. Following surgery, she returned to our hospital, and vancomycin administration continued. The patient was discharged after 31 total days of postoperative antimicrobial therapy. The patient experienced no exacerbations thereafter.ConclusionsWe report the rare case of C. striatum mitral valve NVE in a young adult without structural heart disease or indwelling cardiovascular devices.Clinical trial numberNot applicable.

Methodological Guidelines of the Scientific Community for Human Microbiome Research (CHMR) and the Russian Gastroenterology Association (RGA) on the Use of Probiotics, Prebiotics, Synbiotics, Metabiotics and Functional Foods Enriched with Them for the Treatment and Prevention of Gastrointestinal Diseases in Adults and Children

Aim: to optimize outcomes of the treatment and prevention of gastrointestinal diseases in adults and children. Key points. The Methodological Guidelines contain sections on the terminology, classification, mechanisms of action, requirements for sale in the Russian Federation, requirements for proving the efficacy and safety of probiotics, prebiotics, synbiotics and metabiotics, as well as functional foods enriched with them. An overview of relevant data allowing to include these drugs and products in the treatment an d prevention of gastrointestinal diseases in adults and children is presented. Conclusion. The clinical efficacy of probiotics, prebiotics, synbiotics and metabiotics depends on the specificity and quantity of their components, the dosage form, the regimen and duration of treatment. Products and functional foods with proven efficacy and safety are recommended for the treatment and prevention of gastrointestinal diseases in adults and children.

Primary succession of Bifidobacteria drives pathogen resistance in neonatal microbiota assembly

Human microbiota assembly commences at birth, seeded by both maternal and environmental microorganisms. Ecological theory postulates that primary colonizers dictate microbial community assembly outcomes, yet such microbial priority effects in the human gut remain underexplored. Here using longitudinal faecal metagenomics, we characterized neonatal microbiota assembly for a cohort of 1,288 neonates from the UK. We show that the pioneering neonatal gut microbiota can be stratified into one of three distinct community states, each dominated by a single microbial species and influenced by clinical and host factors, such as maternal age, ethnicity and parity. A community state dominated by Enterococcus faecalis displayed stochastic microbiota assembly with persistent high pathogen loads into infancy. In contrast, community states dominated by Bifidobacterium, specifically B. longum and particularly B. breve, exhibited a stable assembly trajectory and long-term pathogen colonization resistance, probably due to strain-specific functional adaptions to a breast milk-rich neonatal diet. Consistent with our human cohort observation, B. breve demonstrated priority effects and conferred pathogen colonization resistance in a germ-free mouse model. Our findings solidify the crucial role of Bifidobacteria as primary colonizers in shaping the microbiota assembly and functions in early life.

Identification and Characterization of Human Breast Milk and Infant Fecal Cultivable Lactobacilli Isolated in Bulgaria: A Pilot Study.

During the last few decades, the main focus of numerous studies has been on the human breast milk microbiota and its influence on the infant intestinal microbiota and overall health. The presence of lactic acid bacteria in breast milk affects both the quantitative and qualitative composition of the infant gut microbiota. The aim of this study was to assess the most frequently detected cultivable rod-shaped lactobacilli, specific for breast milk of healthy Bulgarian women and fecal samples of their infants over the first month of life, in 14 mother-infant tandem pairs. Additionally, we evaluated the strain diversity among the most common isolated species. A total of 68 Gram-positive and catalase-negative strains were subjected to identification using the MALDI-TOF technique. Predominant cultivable populations belonging to the rod-shaped lactic acid bacteria have been identified as Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, Lacticaseibacillus paracasei, and Limosilactobacillus reuteri. Also, we confirmed the presence of Lactiplantibacillus plantarum and Lactobacillus gasseri. Up to 26 isolates were selected as representatives and analyzed by 16S rRNA sequencing for strain identity confirmation and a phylogenetic tree based on 16S rRNA gene sequence was constructed. Comparative analysis by four RAPD primers revealed genetic differences between newly isolated predominant L. rhamnosus strains. This pilot study provides data for the current first report concerning the investigation of the characteristic cultivable lactobacilli isolated from human breast milk and infant feces in Bulgaria.

Human microbiome: Impact of newly approved treatments on C. difficile infection.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. The primary purposes of this review are to provide a brief overview of the microbiome, discuss the most relevant outcome data and key characteristics of each live microbiome agent, and pose questions for consideration going forward as these agents are integrated into clinical practice. The management of Clostridiodes difficile infection (CDI) remains a difficult clinical conundrum, with recurrent CDI occurring in 15% to 35% of patients and causing significant morbidity and decreased quality of life. For patients with frequent CDI recurrences, fecal microbiota transplantation (FMT) has been demonstrated to have significant benefit but also significant risks, and FMT is not approved by the US Food and Drug Administration (FDA) for that indication. FDA has established a new therapeutic class for agents known as live biotherapeutic products (LBPs) that offer significant advantages over FMT, including standardized screening, testing, and manufacturing as well as known quantities of organisms contained within. Two new live microbiome products within this class were recently approved by FDA for prevention of CDI recurrences in adult patients following treatment for recurrent CDI with standard antimicrobial therapy. Both agents had demonstrated efficacy in registry trials in preventing CDI recurrence but differ significantly in a number of characteristics, such as route of administration. Cost as well as logistics are current obstacles to use of these therapies. Live microbiome therapy is a promising solution for patients with recurrent CDI. Future studies should provide further evidence within yet-to-be-evaluated populations not included in registry studies. This along with real-world evidence will inform future use and clinical guideline placement.

MRGM: an enhanced catalog of mouse gut microbial genomes substantially broadening taxonomic and functional landscapes.

Mouse gut microbiome research is pivotal for understanding the human gut microbiome, providing insights into disease modeling, host-microbe interactions, and the dietary influence on the gut microbiome. To enhance the translational value of mouse gut microbiome studies, we need detailed and high-quality catalogs of mouse gut microbial genomes. We introduce the Mouse Reference Gut Microbiome (MRGM), a comprehensive catalog with 42,245 non-redundant mouse gut bacterial genomes across 1,524 species. MRGM marks a 40% increase in the known taxonomic diversity of mouse gut microbes, capturing previously underrepresented lineages through refined genome quality assessment techniques. MRGM not only broadens the taxonomic landscape but also enriches the functional landscape of the mouse gut microbiome. Using deep learning, we have elevated the Gene Ontology annotation rate for mouse gut microbial proteins from 3.2% with orthology to 60%, marking an over 18-fold increase. MRGM supports both DNA- and marker-based taxonomic profiling by providing custom databases, surpassing previous catalogs in performance. Finally, taxonomic and functional comparisons between human and mouse gut microbiota reveal diet-driven divergences in their taxonomic composition and functional enrichment. Overall, our study highlights the value of high-quality microbial genome catalogs in advancing our understanding of the co-evolution between gut microbes and their host.

A unified web cloud computing platform MiMedSurv for microbiome causal mediation analysis with survival responses

In human microbiome studies, mediation analysis has recently been spotlighted as a practical and powerful analytic tool to survey the causal roles of the microbiome as a mediator to explain the observed relationships between a medical treatment/environmental exposure and a human disease. We also note that, in a clinical research, investigators often trace disease progression sequentially in time; as such, time-to-event (e.g., time-to-disease, time-to-cure) responses, known as survival responses, are prevalent as a surrogate variable for human health or disease. In this paper, we introduce a web cloud computing platform, named as microbiome mediation analysis with survival responses (MiMedSurv), for comprehensive microbiome mediation analysis with survival responses on user-friendly web environments. MiMedSurv is an extension of our prior web cloud computing platform, named as microbiome mediation analysis (MiMed), for survival responses. The two main features that are well-distinguished are as follows. First, MiMedSurv conducts some baseline exploratory non-mediational survival analysis, not involving microbiome, to survey the disparity in survival response between medical treatments/environmental exposures. Then, MiMedSurv identifies the mediating roles of the microbiome in various aspects: (i) as a microbial ecosystem using ecological indices (e.g., alpha and beta diversity indices) and (ii) as individual microbial taxa in various hierarchies (e.g., phyla, classes, orders, families, genera, species). To illustrate its use, we survey the mediating roles of the gut microbiome between antibiotic treatment and time-to-type 1 diabetes. MiMedSurv is freely available on our web server (http://mimedsurv.micloud.kr).

Bacterial association with metals enables in vivo monitoring of urogenital microbiota using magnetic resonance imaging

Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here we investigate longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by elevated cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; up to 60-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in the future may enable monitoring of their persistence in the human body for enhanced molecular imaging.

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.

A streamlined culturomics case study for the human gut microbiota research

Bacterial culturomics is a set of techniques to isolate and identify live bacteria from complex microbial ecosystems. Despite its potential to revolutionize microbiome research, bacterial culturomics has significant challenges when applied to human gut microbiome studies due to its labor-intensive nature. Therefore, we established a streamlined culturomics approach with minimal culture conditions for stool sample preincubation. We evaluated the suitability of non-selective medium candidates for maintaining microbial diversity during a 30-day incubation period based on 16S rRNA gene amplicon analysis. Subsequently, we applied four culture conditions (two preincubation media under an aerobic/anaerobic atmosphere) to isolate gut bacteria on a large scale from eight stool samples of healthy humans. We identified 8141 isolates, classified into 263 bacterial species, including 12 novel species candidates. Our analysis of cultivation efficiency revealed that seven days of aerobic and ten days of anaerobic incubation captured approximately 91% and 95% of the identified species within each condition, respectively, with a synergistic effect confirmed when selected preincubation media were combined. Moreover, our culturomics findings expanded the coverage of gut microbial diversity compared to 16S rRNA gene amplicon sequencing results. In conclusion, this study demonstrated the potential of a streamlined culturomics approach for the efficient isolation of gut bacteria from human stool samples. This approach might pave the way for the broader adoption of culturomics in human gut microbiome studies, ultimately leading to a more comprehensive understanding of this complex microbial ecosystem.