Comparing microbial communities in mucilage and seawater samples: Metagenomic insights into mucilage formation in the Marmara Sea.

Marine environments are subject to various naturally occurring phenomena, including marine snow and mucilage. In 2021, the rapid emergence of mucilage in the Marmara Sea raised concerns about its environmental impact. This study investigates the microbial communities in mucilage and seawater samples from the Marmara Sea using metagenomic-scale comparative analyses. The results indicate significant differences in microbial composition and diversity, with mucilage samples showing higher levels of polysaccharide biosynthesis-related enzymes. Over 50% of reads in mucilage samples remained unclassified (dark matter), highlighting unknown microbial taxa. Clean seawater was characterized by a higher presence of Euryarchaeota, Proteobacteria, and Rhodothermaeota, while Chlamydiae and Fusobacteria were dominant in mucilage. The study underscores the necessity for comprehensive metagenomic analyses to understand microbial roles in mucilage formation and persistence. Early detection of microbial shifts could serve as a warning system for mucilage outbreaks, aiding in the development of management strategies.

The comprehensive evaluation of oral and fecal microbiota in patients with acromegaly.

PURPOSE: The alteration of the microbiota in the mouth and gut could potentially play a role in the pathogenesis of various diseases, and conversely, these diseases may have an influence on the composition of the gut microbiota. Acromegaly disease can potentially affect physiological processes in the mouth and gut. The present study was designed to investigate the relationship between acromegaly and the oral and gut microbiota, as data on this topic are scarce. METHODS: This was a multicenter, cross-sectional study. Our study included individuals diagnosed with acromegaly (who were treated and followed up, and also as an another group of patients with newly diagnosed acromegaly) and healthy participants. All three groups were assessed and compared based on age, sex, serum IGF-1, body mass index BMI as well as their stool and oral microbiota We collected demographic information from the patients, collected fecal and oral samples, performed DNA isolation followed by 16 S rRNA sequencing, and then performed bioinformatic analysis. We also analyzed the oral and fecal samples with respect to medical and surgical treatment and disease control status, specific treatments received for acromegaly, presence of comorbidities, hypopituitarism status, presence of intestinal polyps. RESULTS: One hundred and three patients with acromegaly, 15 newly diagnosed patients with acromegaly without comorbidities and 34 healthy controls were included in the study. The Firmicutes/Bacteroidetes ratio was significantly lower in patients with acromegaly who received treatment (medical and/or surgical) than in healthy controls. In addition, a significant difference was found in the fecal and oral microbiota of patients with acromegaly with disease control compared to healthy controls. Furthermore, a significant difference was found in the fecal and oral microbiota of patients with acromegaly without disease control. Nevertheless, it was not possible to establish a clear relationship between disease control status, the presence of intestinal polyps, the presence of type 2 diabetes and the composition of the oral and gut microbiota in acromegalic patients who had received different forms of treatment. CONCLUSION: Patients with acromegaly show distinct gut microbiota profiles, and it is evident that factors beyond the GH/IGF-1 axis play a role in shaping the gut microbiota of individuals with acromegaly.

A Shotgun Metagenomics Investigation into Labeling Inaccuracies in Widely Sold Probiotic Supplements in the USA.

While probiotics are generally considered safe, concerns persist regarding the accuracy of labels on these supplements and their potential contribution to the spread of antibiotic resistance genes. Given that probiotics are predominantly ingested with a view towards obtaining particular health benefits. The objective of this study is to assess the composition of 50 widely available probiotic supplements in the USA using shotgun metagenome sequencing. The study also determines the potential resistome profile, and the functional characteristics of these products. This study finds that 67% of products does not contain any labeling inaccuracies. Antimicrobial Resistance Genes (ARGs) are identified in several products, particularly Bacillus-based products carrying between 10 and 56 genes. The risk posed by the presence of these ARGs requires further study. Functional analysis reveals differences in metabolic profiles among probiotic supplements, indicating the importance of strain-level selection for personalized probiotics. This study provides updated and comprehensive analysis to evaluate a snapshot of the USA market. The study demonstrates that label inaccuracies occur on approximately one third of popular dietary supplement products sold in the USA, supporting the need for improved approaches to marketing and quality control. Further, the risk of antibiotic resistance, especially in Bacillus-based formulations, should be assessed.

Clonal spread of trimethoprim-sulfamethoxazole-resistant Stenotrophomonas maltophilia isolates in a tertiary hospital.

Aim: The aims of this study were to: (i) determine antibiotic susceptibility of clinical Stenotrophomonas maltophilia isolates, (ii) investigate the presence of different classes of integrons and sul genes responsible for sulphonamide resistance, (iii) assess the molecular epidemiology of the isolates by determining their clonal relatedness, and (iv) investigate the potential sources of infection by collecting environmental samples when necessary. Methods: 99 S. maltophilia isolates from clinical specimens of hospitalized patients were screened by PCR for sul1, sul2, sul3 genes, and integron-associated integrase genes: intI1, intI2, and intI3. PFGE was used to determine the clonal relatedness of the isolates. Results: Susceptibility rates for trimethoprim-sulfamethoxazole, levofloxacin, and ceftazidime were 90.9%, 91.9%, and 53.5% respectively. All trimethoprim-sulfamethoxazole-resistant isolates were positive for intI1 and sul1. PFGE analysis revealed that 24 of the isolates were clonally related, clustering in seven different clones. Five of the nine trimethoprim-sulfamethoxazole-resistant isolates were clonally related. The first isolate in this clone was from a wound sample of a patient in the infectious diseases clinic, and the other four were isolated from the bronchoalveolar lavage samples of patients in the thoracic surgery unit. The patient with the first isolate neither underwent bronchoscopy nor stayed in the thoracic surgery unit. Although clustering was observed in bronchoalveolar lavage samples, no S. maltophilia growth was detected in environmental samples. Conclusion: The findings demonstrated that the sul1 gene carried by class 1 integrons plays an important role in trimethoprim-sulfamethoxazole resistance in S. maltophilia isolates. PFGE analysis revealed a high degree of genetic diversity. However, detection of clonally related isolates suggests the acquisition from a common source and/or cross-transmission of this microorganism between the patients.

Modulation of the skin and gut microbiome by psoriasis treatment: a comprehensive systematic review.

The microbiome is intricately linked to the development of psoriasis, serving as both a potential cause and consequence of the psoriatic process. In recent years, there has been growing interest among psoriasis researchers in exploring how psoriasis treatments affect the skin and gut microbiome. However, a comprehensive evaluation of the impact of modern treatment approaches on the microbiome has yet to be conducted. In this systematic review, we analyze studies investigating alterations in the skin and gut microbiome resulting from psoriasis treatment, aiming to understand how current therapies influence the role of the microbiome in psoriasis development. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed and Scopus databases were searched for eligible studies from the inception dates until July 5, 2023. Study selection, data extraction, and risk of bias assessment were carried out by three overlapping pairs of reviewers, resolving any disagreements through consensus. Our analysis of various treatments, including biologics, conventional medications, phototherapy, and probiotics, reveals significant shifts in microbial diversity and abundance. Importantly, favorable treatment outcomes are associated with microbiota alterations that approach those observed in healthy individuals. While the studies reviewed exhibit varying degrees of bias, underscoring the need for further research, this review supports the potential of microbiome modulation as both a preventive and therapeutic strategy for psoriasis patients. The findings underscore the importance of personalized therapeutic approaches, recognizing the profound impact of treatment on the microbiome. They also highlight the promise of probiotics, prebiotics, and dietary interventions in psoriasis management.

A Multicenter Randomized Controlled Trial of Microbiome-Based Artificial Intelligence-Assisted Personalized Diet vs Low-Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols Diet: A Novel Approach for the Management of Irritable Bowel Syndrome.

INTRODUCTION: Personalized management strategies are pivotal in addressing irritable bowel syndrome (IBS). This multicenter randomized controlled trial focuses on comparing the efficacy of a microbiome-based artificial intelligence-assisted personalized diet (PD) with a low-fermentable oligosaccharides, disaccharides, monosaccharides, and polyols diet (FODMAP) for IBS management. METHODS: One hundred twenty-one patients participated, with 70 assigned to the PD group and 51 to the FODMAP diet group. IBS subtypes, demographics, symptom severity (IBS-SSS), anxiety, depression, and quality of life (IBS-QOL) were evaluated. Both interventions spanned 6 weeks. The trial's primary outcome was the within-individual difference in IBS-SSS compared between intervention groups. RESULTS: For the primary outcome, there was a change in IBS-SSS of -112.7 for those in the PD group vs -99.9 for those in the FODMAP diet group ( P = 0.29). Significant improvement occurred in IBS-SSS scores ( P < 0.001), frequency ( P < 0.001), abdominal distension ( P < 0.001), and life interference ( P < 0.001) in both groups. In addition, there were significant improvements in anxiety levels and IBS-QOL scores for both groups ( P < 0.001). Importantly, PD was effective in reducing IBS SSS scores across all IBS subtypes IBS-Constipation (IBS-C; P < 0.001), IBS-Diarrhea (IBS-D; P = 0.01), and IBS-Mixed (IBS-M; P < 0.001) while FODMAP diet exhibited comparable improvements in IBS-C ( P = 0.004) and IBS-M ( P < 0.001). PD intervention significantly improved IBS-QOL scores for all subtypes (IBS-C [ P < 0.001], IBS-D [ P < 0.001], and IBS-M [ P = 0.008]) while the FODMAP diet did so for the IBS-C ( P = 0.004) and IBS-D ( P = 0.022). Notably, PD intervention led to significant microbiome diversity shifts ( P < 0.05) and taxa alterations compared with FODMAP diet. DISCUSSION: The artificial intelligence-assisted PD emerges as a promising approach for comprehensive IBS management. With its ability to address individual variation, the PD approach demonstrates significant symptom relief, enhanced QOL, and notable diversity shifts in the gut microbiome, making it a valuable strategy in the evolving landscape of IBS care.

16S rRNA sequencing reveals microbiota differences in orthopedic implants between aseptic loosening and prosthetic joint infection cases.

Prosthetic joint infection (PJI) and aseptic loosening (AL) are common complications of total joint arthroplasty. An accumulation of evidence indicates the presence of microbial communities on prosthetic implants, but the overall microbial profile is unclear. In this study, we aimed to investigate the differences in the microbial composition of prosthetic implants obtained from PJI and AL patients using the 16S rRNA sequencing method. Patients who underwent revision hip, knee, or shoulder arthroplasty caused by PJI (n = 20) or AL (n = 10) were enrolled in the study. 16S rRNA sequencing targeting the V3-V4 region was performed on the microbial specimens collected from synovial fluid, periprosthetic deep-tissue, and biofilm during the revision surgery. The sequenced raw data were analysed for microbial composition and ecological and differential abundance analyses using bioinformatics tools. The AL group had relatively balanced and higher diversity, with Staphylococcus, Streptococcus, and Veillonella being prominent. In the PJI group, Staphylococcus and Pseudomonas were predominant, especially in deep-tissue samples and biofilm samples, respectively. The differential abundance analysis identified 15 and 2 distinctive taxa in the AL and PJI groups, respectively. Our findings provided preliminary insights supporting the existence of periprosthetic microbiota in orthopedic implants and explaining the differences in microbial composition between the AL and PJI groups.

A toolbox of machine learning software to support microbiome analysis.

The human microbiome has become an area of intense research due to its potential impact on human health. However, the analysis and interpretation of this data have proven to be challenging due to its complexity and high dimensionality. Machine learning (ML) algorithms can process vast amounts of data to uncover informative patterns and relationships within the data, even with limited prior knowledge. Therefore, there has been a rapid growth in the development of software specifically designed for the analysis and interpretation of microbiome data using ML techniques. These software incorporate a wide range of ML algorithms for clustering, classification, regression, or feature selection, to identify microbial patterns and relationships within the data and generate predictive models. This rapid development with a constant need for new developments and integration of new features require efforts into compile, catalog and classify these tools to create infrastructures and services with easy, transparent, and trustable standards. Here we review the state-of-the-art for ML tools applied in human microbiome studies, performed as part of the COST Action ML4Microbiome activities. This scoping review focuses on ML based software and framework resources currently available for the analysis of microbiome data in humans. The aim is to support microbiologists and biomedical scientists to go deeper into specialized resources that integrate ML techniques and facilitate future benchmarking to create standards for the analysis of microbiome data. The software resources are organized based on the type of analysis they were developed for and the ML techniques they implement. A description of each software with examples of usage is provided including comments about pitfalls and lacks in the usage of software based on ML methods in relation to microbiome data that need to be considered by developers and users. This review represents an extensive compilation to date, offering valuable insights and guidance for researchers interested in leveraging ML approaches for microbiome analysis.

The role of the Mediterranean diet in modulating the gut microbiome: A review of current evidence.

The Mediterranean diet (MedDiet) is recognized as one of the United Nations Educational, Scientific and Cultural Organization Intangible Cultural Heritage assets associated with lower rates of cardiometabolic diseases; lower prevalence of cancer, Alzheimer's disease, depression, and onset of inflammatory bowel disease; and more generally low-grade inflammation and mortality risks. Beyond being an input source of beneficial micronutrients, it recently has been discovered that the MedDiet plays a role in a more complex human microbiome-mediated mechanism. An interesting hypothesis suggests a bidirectional relationship between the MedDiet and the gut microbiome, where gut microbiota assembly and biosynthetic capacity are responsive to the diet; in return, the microbiome-reachable nutrients shape and modulate the microbiome toward a characteristic probiotic state. It can be speculated that that primary health benefits of the MedDiet exerted via the gut microbiome are mediated by the bioactive compounds transformed by the microbiome. Furthermore, it is possible that additional probiotic properties of the organisms promoted by diet adherence have secondary benefits. As more detailed omic-based studies take place, more evidence on the MedDiet as a core generic probiotic microbiome modulation strategy surface. However, individual-specific microbiome compositions might impose personal variations on the diet outcome. Therefore, a prospective strategy of a fine-tuned precision nutrition approach might deliver optimized benefits of the MedDiet.

Potential associations between alterations in gut microbiome and obesity-related traits after the bariatric surgery.

BACKGROUND: This study aimed to examine the effects of both obesity and bariatric surgery on gut microbiome, dietary intake, as well as metabolic and inflammatory parameters. METHODS: All participants (15 with morbid obesity who had bariatric surgery, 8 with morbid obesity and 11 non-obese) were followed up for a 6-month period with interviews at baseline (M0), at the end of 3 (M3) and 6 months (M6). Dietary assessment was done, and blood and faecal samples were collected. RESULTS: Dietary energy and nutrient intakes as well as serum glucose levels, total cholesterol, low-density lipoprotein (LDL)-cholesterol and high sensitivity C-reactive protein (hs-CRP) levels decreased after surgery (p < 0.05, for each). Participants with morbid obesity had higher levels of Firmicutes and lower levels of Bacteroidetes at M0 compared to non-obese participants. The abundances of Bacteroidetes increased (p = 0.02), whereas that of Firmicutes decreased (p > 0.05) after the surgery, leading to a significant decrease in Firmicutes/Bacteroidetes ratio (p = 0.01). At sub-phylum level, the abundances of Lactobacillus and Bifidobacterium decreased, whereas those of Akkermansia increased after the surgery (p < 0.01, for each). Although participants who were morbidly obese had a distinct profile according to ß-diversity indices at M0, it became similar with the profile of non-obese participants (p > 0.05) at M3 and M6. Similarly, α-diversity indices were lower in subjects with morbid obesity at M0, but became similar to levels in non-obese controls at M6. CONCLUSION: This study confirmed that bariatric surgery has substantial impacts on gut microbiome's composition and diversity, as well as anthropometrical measurements and biochemical parameters, which were associated with the alterations in dietary intake patterns.

A comparative study of the clonal diversity and virulence characteristics of uropathogenic Escherichia coli isolated from Australian and Turkish (Turkey) children and adults with urinary tract infections.

Introduction: The virulence-associated gene (VAG) repertoire and clonal organization of uropathogenic Escherichia coli (UPEC) strains is influenced by host demographic, geographic locale, and the setting of urinary tract infection (UTI). Nevertheless, a direct comparison of these features among Australian and Turkish UPEC remains unexplored. Accordingly, this study investigated the clonal composition and virulence characteristics of a collection of UPEC isolated from Australian and Turkish UTI patients. Methods: A total of 715 UPEC strains isolated from Australian (n=361) and Turkish (n=354) children and adults with hospital (HA)- and community-acquired (CA)-UTIs were included in this study. Typing of the strains using RAPD-PCR and PhPlate fingerprinting grouped all strains into 25 clonal groups (CGs). CG representatives were phylogrouped and screened for the presence of 18 VAGs associated with extraintestinal pathogenic E. coli. Results: Turkish UPEC strains were characterized by high clonal diversity and predominance of the phylogroup D, while few distinct clonal groups with phylogenetic group B2 backgrounds dominated among the Australian strains. Twelve identical CGs were shared between ≥1 patient group from either country. Australian strains, particularly those isolated from children with HA-UTI, showed higher virulence potential than their Turkish counterparts, carrying significantly more genes associated with adhesion, iron acquisition and capsule biosynthesis. Conclusions: This study identified identical CGs of UPEC causing HA- and CA-UTIs among Australian and Turkish UTI patients. These CGs frequently carried VAGs associated with adhesion, iron acquisition, immune evasion, and toxin production, which may contribute to their ability to disseminate internationally and to cause UTI.

Efficacy of AI-Assisted Personalized Microbiome Modulation by Diet in Functional Constipation: A Randomized Controlled Trial.

Background: Currently, medications and behavioral modifications have limited success in the treatment of functional constipation (FC). An individualized diet based on microbiome analysis may improve symptoms in FC. In the present study, we aimed to investigate the impacts of microbiome modulation on chronic constipation. Methods: Between December 2020−December 2021, 50 patients fulfilling the Rome IV criteria for functional constipation were randomized into two groups. The control group received sodium picosulfate plus conventional treatments (i.e., laxatives, enemas, increased fiber, and fluid intake). The study group underwent microbiome analysis and received an individualized diet with the assistance of a soft computing system (Enbiosis Biotechnology®, Sariyer, Istanbul). Differences in patient assessment constipation−quality of life (PAC-QoL) scores and complete bowel movements per week (CBMpW) were compared between groups after 6-weeks of intervention. Results: The mean age of the overall cohort (n = 45) was 31.5 ± 10.2 years, with 88.9% female predominance. The customized diet developed for subjects in the study arm resulted in a 2.5-fold increase in CBMpW after 6-weeks (1.7 vs. 4.3). The proportion of the study group patients with CBMpW > 3 was 83% at the end of the study, and the satisfaction score was increased 4-fold from the baseline (3.1 to 10.7 points). More than 50% improvement in PAC-QoL scores was observed in 88% of the study cohort compared to 40% in the control group (p = 0.001). Conclusion: The AI-assisted customized diet based on individual microbiome analysis performed significantly better compared to conventional therapy based on patient-reported outcomes in the treatment of functional constipation.

Artificial intelligence-based personalized diet: A pilot clinical study for irritable bowel syndrome.

We enrolled consecutive IBS-M patients (n = 25) according to Rome IV criteria. Fecal samples were obtained from all patients twice (pre-and post-intervention) and high-throughput 16S rRNA sequencing was performed. Six weeks of personalized nutrition diet (n = 14) for group 1 and a standard IBS diet (n = 11) for group 2 were followed. AI-based diet was designed based on optimizing a personalized nutritional strategy by an algorithm regarding individual gut microbiome features. The IBS-SSS evaluation for pre- and post-intervention exhibited significant improvement (p < .02 and p < .001 for the standard IBS diet and personalized nutrition groups, respectively). While the IBS-SSS evaluation changed to moderate from severe in 78% (11 out of 14) of the personalized nutrition group, no such change was observed in the standard IBS diet group. A statistically significant increase in the Faecalibacterium genus was observed in the personalized nutrition group (p = .04). Bacteroides and putatively probiotic genus Propionibacterium were increased in the personalized nutrition group. The change (delta) values in IBS-SSS scores (before-after) in personalized nutrition and standard IBS diet groups are significantly higher in the personalized nutrition group. AI-based personalized microbiome modulation through diet significantly improves IBS-related symptoms in patients with IBS-M. Further large-scale, randomized placebo-controlled trials with long-term follow-up (durability) are needed.

SERS-based sensor with a machine learning based effective feature extraction technique for fast detection of colistin-resistant Klebsiella pneumoniae.

Colistin-resistant Klebsiella pneumoniae (ColR-Kp) causes high mortality rates since colistin is used as the last-line antibiotic against multi-drug resistant Gram-negative bacteria. To reduce infections and mortality rates caused by ColR-Kp fast and reliable detection techniques are vital. In this study, we used a label-free surface-enhanced Raman scattering (SERS)-based sensor with machine learning algorithms to discriminate colistin-resistant and susceptible strains of K. pneumoniae. A total of 16 K. pneumoniae strains were incubated in tryptic soy broth (TSB) for 4 h. Collected SERS spectra of ColR-Kp and colistin susceptible K. pneumoniae (ColS-Kp) have shown some spectral differences that hard to discriminate by the naked eye. To extract discriminative features from the dataset, autoencoder and principal component analysis (PCA) that extract features in a non-linear and linear manner, respectively were performed. Extracted features were fed into the support vector machine (SVM) classifier to discriminate K. pneumoniae strains. Classifier performance was evaluated by using features extracted by each feature extraction techniques. Classification results of SVM classifier with extracted features by an autoencoder (autoencoder-SVM) has shown better performance than SVM classifier with extracted features by PCA (PCA-SVM). The accuracy, sensitivity, specificity, and area under curve (AUC) value of the autoencoder-SVM model were found as 94%, 94.2%, 93.8%, and 0.98, respectively. Furthermore, the autoencoder-SVM model has demonstrated statistically significantly better classifier performance than PCA-SVM in terms of accuracy and AUC values. These results illustrate that non-linear features can be more discriminative than linear ones to determine SERS spectral data of antibiotic-resistant and susceptible bacteria. Our methodological approach enables rapid and high accuracy detection of ColR-Kp and ColS-Kp, suggesting that this can be a promising tool to limit colistin resistance.

Acromegaly is associated with a distinct oral and gut microbiota.

PURPOSE: Our aim was to investigate the changes in the composition of oral and gut microbiota in patients with newly diagnosed acromegaly and their relationship with IGF-1 levels. METHODS: Oral and fecal samples were collected from patients with newly diagnosed acromegaly without comorbidities and from healthy controls. The composition of the microbiota was analyzed. The general characteristics, oral and stool samples of the patients and healthy control subjects were compared. The changes in microbiota composition in both habitats, their correlations and associations with IGF-1 were statistically observed using machine learning models. RESULTS: Fifteen patients with newly diagnosed acromegaly without comorbidities and 15 healthy controls were included in the study. There was good agreement between fecal and oral microbiota in patients with acromegaly (p = 0.03). Oral microbiota diversity was significantly increased in patients with acromegaly (p < 0.01). In the fecal microbiota, the Firmicutes/Bacteroidetes ratio was lower in patients with acromegaly than in healthy controls (p = 0.011). Application of the transfer learned model to the pattern of microbiota allowed us to identify the patients with acromegaly with perfect accuracy. CONCLUSIONS: Patients with acromegaly have their own oral and gut microbiota even if they do not have acromegaly-related complications. Moreover, the excess IGF-1 levels could be correctly predicted based on the pattern of the microbiome.

Stratification of the Gut Microbiota Composition Landscape across the Alzheimer's Disease Continuum in a Turkish Cohort.

Alzheimer's disease (AD) is a heterogeneous disorder that spans a continuum with multiple phases, including preclinical, mild cognitive impairment, and dementia. Unlike for most other chronic diseases, human studies reporting on AD gut microbiota in the literature are very limited. With the scarcity of approved drugs for AD therapies, the rational and precise modulation of gut microbiota composition using diet and other tools is a promising approach to the management of AD. Such an approach could be personalized if an AD continuum can first be deconstructed into multiple strata based on specific microbiota features by using single or multiomics techniques. However, stratification of AD gut microbiota has not been systematically investigated before, leaving an important research gap for gut microbiota-based therapeutic approaches. Here, we analyze 16S rRNA amplicon sequencing of stool samples from 27 patients with mild cognitive impairment, 47 patients with AD, and 51 nondemented control subjects by using tools compatible with the compositional nature of microbiota. To stratify the AD gut microbiota community, we applied four machine learning techniques, including partitioning around the medoid clustering and fitting a probabilistic Dirichlet mixture model, the latent Dirichlet allocation model, and we performed topological data analysis for population-scale microbiome stratification based on the Mapper algorithm. These four distinct techniques all converge on Prevotella and Bacteroides stratification of the gut microbiota across the AD continuum, while some methods provided fine-scale resolution in stratifying the community landscape. Finally, we demonstrate that the signature taxa and neuropsychometric parameters together robustly classify the groups. Our results provide a framework for precision nutrition approaches aiming to modulate the AD gut microbiota. IMPORTANCE The prevalence of AD worldwide is estimated to reach 131 million by 2050. Most disease-modifying treatments and drug trials have failed, due partly to the heterogeneous and complex nature of the disease. Recent studies demonstrated that gut dybiosis can influence normal brain function through the so-called "gut-brain axis." Modulation of the gut microbiota, therefore, has drawn strong interest in the clinic in the management of the disease. However, there is unmet need for microbiota-informed stratification of AD clinical cohorts for intervention studies aiming to modulate the gut microbiota. Our study fills in this gap and draws attention to the need for microbiota stratification as the first step for microbiota-based therapy. We demonstrate that while Prevotella and Bacteroides clusters are the consensus partitions, the newly developed probabilistic methods can provide fine-scale resolution in partitioning the AD gut microbiome landscape.

Temporal overexpression of IL-22 and Reg3γ differentially impacts the severity of experimental autoimmune encephalomyelitis.

IL-22 is an alpha-helical cytokine which belongs to the IL-10 family of cytokines. IL-22 is produced by RORγt+ innate and adaptive lymphocytes, including ILC3, γδ T, iNKT, Th17 and Th22 cells and some granulocytes. IL-22 receptor is expressed primarily by non-haematopoietic cells. IL-22 is critical for barrier immunity at the mucosal surfaces in the steady state and during infection. Although IL-22 knockout mice were previously shown to develop experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis (MS), how temporal IL-22 manipulation in adult mice would affect EAE course has not been studied previously. In this study, we overexpressed IL-22 via hydrodynamic gene delivery or blocked it via neutralizing antibodies in C57BL/6 mice to explore the therapeutic impact of IL-22 modulation on the EAE course. IL-22 overexpression significantly decreased EAE scores and demyelination, and reduced infiltration of IFN-γ+IL-17A+Th17 cells into the central nervous system (CNS). The neutralization of IL-22 did not alter the EAE pathology significantly. We show that IL-22-mediated protection is independent of Reg3γ, an epithelial cell-derived antimicrobial peptide induced by IL-22. Thus, overexpression of Reg3γ significantly exacerbated EAE scores, demyelination and infiltration of IFN-γ+IL-17A+ and IL-17A+GM-CSF+Th17 cells to CNS. We also show that Reg3γ may inhibit IL-2-mediated STAT5 signalling and impair expansion of Treg cells in vivo and in vitro. Finally, Reg3γ overexpression dramatically impacted intestinal microbiota during EAE. Our results provide novel insight into the role of IL-22 and IL-22-induced antimicrobial peptide Reg3γ in the pathogenesis of CNS inflammation in a murine model of MS.

Gut microbiota in patients with newly diagnosed acromegaly: a pilot cross-sectional study.

PURPOSE: Microbiota has crucial biological importance for human well-being. Bidirectional interaction exists between microbiota and the host, and there have been no studies investigating this interaction in patients with acromegaly. We aimed to analyze the composition of microbiota in patients with newly diagnosed acromegaly. METHOD: Stool samples were obtained from the patients with newly diagnosed acromegaly in the Endocrinology Clinic of Erciyes University Medical School. The composition of microbiota was analyzed, and the results were compared to healthy volunteers matched to the patients in terms of age, gender and body mass index. RESULTS: Seven patients (three male, four female) with a mean age of 48 ± 17.6 years were included in the study. The stool analysis revealed a significantly lower bacterial diversity in the patients with acromegaly. Bacteroidetes phylum was predominating in the patient group, and Firmicutes/Bacteroidetes ratio was altered significantly. Bifidobacterium, Collinsella, Bacteroides, Butyricimonas, Clostridium, Oscillospira, and Dialister were predominating in the control group. CONCLUSION: The gut microbiota is significantly altered in patients with newly diagnosed acromegaly. Further prospective studies are needed to elucidate the causative relationship between acromegaly, colorectal pathologies, and microbial alterations.

Statistical and Machine Learning Techniques in Human Microbiome Studies: Contemporary Challenges and Solutions.

The human microbiome has emerged as a central research topic in human biology and biomedicine. Current microbiome studies generate high-throughput omics data across different body sites, populations, and life stages. Many of the challenges in microbiome research are similar to other high-throughput studies, the quantitative analyses need to address the heterogeneity of data, specific statistical properties, and the remarkable variation in microbiome composition across individuals and body sites. This has led to a broad spectrum of statistical and machine learning challenges that range from study design, data processing, and standardization to analysis, modeling, cross-study comparison, prediction, data science ecosystems, and reproducible reporting. Nevertheless, although many statistics and machine learning approaches and tools have been developed, new techniques are needed to deal with emerging applications and the vast heterogeneity of microbiome data. We review and discuss emerging applications of statistical and machine learning techniques in human microbiome studies and introduce the COST Action CA18131 "ML4Microbiome" that brings together microbiome researchers and machine learning experts to address current challenges such as standardization of analysis pipelines for reproducibility of data analysis results, benchmarking, improvement, or development of existing and new tools and ontologies.

Effect of essential oil supplementation to diet on meat quality, fatty acid composition, performance parameters and intestinal microbiota of Japanese quails.

The effect of essential oil (EO) supplementation on carcass characteristics of Japanese quails and interactions between ingredients and intestinal morphology were investigated in this study. A total of 250 quails were fed different diet: D1, basal diet (BD); D2, BD plus palmarosa oil (PO; 100 µg/kg diet); D3, BD plus lemon myrtle oil (LMO; 100 µg/kg diet); D4, BD plus α-Tops (mixture of α-terpineol, cineole and terpinene-4-ol; 100 µg/kg diet); and D5, BD plus cyclodextrin. Overall growth performance was determined at multiple time points during 35 days of experiment. Carcass characteristics (fatty acid, pH and colour), intestinal morphology and the expression levels of meat quality-related genes including the insulin-like growth factor (IGF-1), myogenin and avian uncoupling protein (avUCP) were examined at the end of the trial. Additionally, intestinal microbiome of quails was studied by next-generation sequencing-based culture-independent analysis. Although the inclusion of EOs into the diet had no effect on the growth performance of quails and the microbial profile, the significant changes in pH24 and colour (a*) of the quail's breast muscle (p < .05) in the group receiving PO were observed. Additionally, oleic acid content in the breast muscle was significantly higher in the EOs supplemented groups (p < .01). Quails fed the PO supplemented diet had higher villus and relatively rich in oleic acid. The expression levels of IGF-1 and myogenin genes in quail's muscle were not affected, but the expression of avUCP gene was significantly lower in quails fed with LMO and α-Tops (p < .05). The results demonstrated variable effects of these treatments on intestinal morphology. Taken together, dietary inclusion of EOs is found to be beneficial and hence can be recommended for improving the quality of poultry meat.