Distinct Microbiome Profiles Research Articles

Tumor microbiome differences in early-onset versus average-onset pancreatic adenocarcinoma.

4016 Background: The rise in early-onset gastrointestinal cancers includes an increased risk of pancreatic adenocarcinoma (PDAC), but the underlying pathogenesis is incompletely understood. The tumor microbiome is an increasing focus of research given its impact on tumor pathogenesis and outcomes. We evaluated microbiome profiles in resected specimens from early-onset PDAC (eoPDAC) and average-onset PDAC (aoPDAC). Methods: PDAC specimens were selected consecutively from Cleveland Clinic and Roswell Park Cancer Institute biorepositories and categorized on age at diagnosis ( < 50 years defined as eoPDAC, and > 50 years as aoPDAC). The tissue microbiome was characterized using shotgun metagenomic sequencing. Alpha diversity, denoting the richness and evenness of microbial species within a specific sample, was compared using the Wilcoxon rank-sum test. The differential test of Beta-diversity distances (Bray Curtis distance), representing microbial taxonomic differences between the specimens was performed using Permutational MANOVA. All p-values were adjusted for multiple testing. Results: The study comprised 44 individuals with resected PDAC (24 eoPDAC and 20 aoPDAC). After quality checks, 63 tissue specimens were selected for analysis (13 tumor and 10 adjacent normal specimens for eoPDAC, 20 each of tumor and adjacent normal specimens for aoPDAC). eoPDAC tumor demonstrated significantly higher alpha diversity compared to adjacent normal tissue (P = 0.02) and aoPDAC (P = 0.0062) while aoPDAC did not (tumor vs normal alpha diversity P = 0.31). Beta diversity analysis demonstrated significantly different diversity of genera between all the groups (P < 0.05). Consistent with this finding, the majority of the species - 259/302 (85.8%) in eo vs aoPDAC comparison and 262/366 (71.6%) for eoPDAC vs normal comparison did not overlap. Differential abundance analysis revealed a significant variation of tumor microbiome in eoPDAC vs aoPDAC (P < 0.05). Prevalent bacterial genera (tumor specimens) are listed in the Table. eoPDAC tumor tissues were enriched in Enterobacter, Neisseria,and Escherichia genera, while aoPDAC tumor tissues were enriched in Klebsiella and Bacillus genera. Conclusions: eoPDAC has a distinct microbiome profile compared to aoPDAC. The correlation with several microbial genera associated with pancreatic diseases is a significant finding and warrants further exploration. This is relevant considering the rising incidence of eoPDAC of unknown etiology, and ongoing efforts to develop microbiome-based biomarkers for screening and treatment. [Table: see text]

Traditional Chinese herbal formulas modulate gut microbiome and improve insomnia in patients with distinct syndrome types: insights from an interventional clinical study.

Traditional Chinese medicine (TCM) comprising herbal formulas has been used for millennia to treat various diseases, such as insomnia, based on distinct syndrome types. Although TCM has been proposed to be effective in insomnia through gut microbiota modulation in animal models, human studies remain limited. Therefore, this study employs machine learning and integrative network techniques to elucidate the role of the gut microbiome in the efficacies of two TCM formulas - center-supplementing and qi-boosting decoction (CSQBD) and spleen-tonifying and yin heat-clearing decoction (STYHCD) - in treating insomnia patients diagnosed with spleen qi deficiency and spleen qi deficiency with stomach heat. Sixty-three insomnia patients with these two specific TCM syndromes were enrolled and treated with CSQBD or STYHCD for 4 weeks. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) every 2 weeks. In addition, variations in gut microbiota were evaluated through 16S rRNA gene sequencing. Stress and inflammatory markers were measured pre- and post-treatment. At baseline, patients exhibiting only spleen qi deficiency showed slightly lesser severe insomnia, lower IFN-α levels, and higher cortisol levels than those with spleen qi deficiency with stomach heat. Both TCM syndromes displayed distinct gut microbiome profiles despite baseline adjustment of PSQI, ISI, and IFN-α scores. The nested stratified 10-fold cross-validated random forest classifier showed that patients with spleen qi deficiency had a higher abundance of Bifidobacterium longum than those with spleen qi deficiency with stomach heat, negatively associated with plasma IFN-α concentration. Both CSQBD and STYHCD treatments significantly improved sleep quality within 2 weeks, which lasted throughout the study. Moreover, the gut microbiome and inflammatory markers were significantly altered post-treatment. The longitudinal integrative network analysis revealed interconnections between sleep quality, gut microbes, such as Phascolarctobacterium and Ruminococcaceae, and inflammatory markers. This study reveals distinct microbiome profiles associated with different TCM syndrome types and underscores the link between the gut microbiome and efficacies of Chinese herbal formulas in improving insomnia. These findings deepen our understanding of the gut-brain axis in relation to insomnia and pave the way for precision treatment approaches leveraging TCM herbal remedies.

Specific Microbiome Signature Dynamics Could Predict Aging Continuum and Cognitive Impairment in Older Adults

The global population is aging, facing a substantial burden of age-related disorders, including cognitive impairment (CI), Alzheimer's disease (AD), and related dementias (ADRD). The lack of effective strategies for preventing and treating these conditions can be attributed to our incomplete understanding of the biology of aging. Emerging evidence strongly suggests that the gut microbiome plays a pivotal role in aging and its association with cognitive decline and ADRD. Yet, the transformations occurring within the microbiome during the aging continuum remain insuffciently studied. We have addressed these significant knowledge gaps by analysing samples and data from 176 older adults participating in the multi-site Microbiome in Aging Gut and Brain (MiaGB) consortium. Whole-genome metagenomic analysis unveiled distinct microbiome profiles among three aging categories: (i) 60-69 (n=62), (ii) 70-79 (n=78), and (iii) 80+ (n=36), spanning from phyla to species-level phylogeny. Notably, in older adults, changes in the microbiome were observed with respect to the aging continuum and cognitive impairment (CI). The abundance of Lachnospiraceae, Eggerthellaceae, Dorea, Blautia, and Eggerthella decreased, while Veillonellaceae increased in the gut of older adults with CI but not within the aging continuum. Interestingly, only Proteobacteria, Firmicutes, Candidatus melainabacteria, Coriobactericeae, Ruminococcaceae, Anerostipe hadrus, and Collinsella aerofaciens decreased, while Bacteroidetes, Bacteroidiceae, and Bacteroides uniformis increased within the aging continuum but were not impacted in CI sub-groups. However, both Ruminococcus torques and Streptococcus thermophilus decreased with aging continuum and CI. These results indicate unique microbiome changes specific to the aging continuum, as well as distinct changes with CI, independent of age. Thus, they not only hold promise as prognostic markers for assessing the risk of cognitive decline and dementia in older adults but also pave the way for designing precision microbiome interventions to mitigate the risks posed by these debilitating public health issues. We thank the Ed and Ethel Moore Alzheimer’s Disease Research Program, Florida Department of Health (22A17), National Institutes of Health, National Institute of Aging (R56AG069676, R56AG064075, RF1AG071762, R21AG072379, U01AG076928), and Department of Defense (W81XWH-18-PRARP AZ180098) for funding support. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Microbiome variations among age classes and diets of captive Asian elephants (Elephas maximus) in Thailand using full-length 16S rRNA nanopore sequencing

Asian elephant (Elephas maximus) is the national symbol of Thailand and linked to Thai history and culture for centuries. The elephant welfare improvement is one of the major components to achieve sustainable captive management. Microbiome inhabiting digestive tracts have been shown with symbiotic relations to host health. This work provided high-resolution microbiome profiles of 32 captive elephants at a species level by utilizing full-length 16S rRNA gene nanopore sequencing. Eleven common uncultured bacterial species were found across elephants fed with solid food including uncultured bacterium Rikenellaceae RC9 gut group, Kiritimatiellae WCHB1-41, Phascolarctobacterium, Oscillospiraceae NK4A214 group, Christensenellaceae R-7 group, Oribacterium, Oscillospirales UCG-010, Lachnospiraceae, Bacteroidales F082, uncultured rumen Rikenellaceae RC9 gut group, and Lachnospiraceae AC2044 group. We observed microbiome shifts along the age classes of baby (0–2 years), juvenile (2–10 years), and adult (> 10 years). Interestingly, we found distinct microbiome profiles among adult elephants fed with a local palm, Caryota urens, as a supplement. Potential beneficial microbes have been revealed according to the age classes and feed diets. The retrieved microbiome data could be provided as good baseline microbial profiles for monitoring elephant health, suggesting further studies towards dietary selection suitable for each age class and the use of local supplementary diets.

Assessment of bacterial and viral gut communities in healthy and tumoral colorectal tissue using RNA and DNA deep sequencing.

Colorectal cancer (CRC) is known to present a distinct microbiome profile compared to healthy mucosa. Non-targeted deep-sequencing strategies enable nowadays full microbiome characterization up to species level. We aimed to analyze both bacterial and viral communities in CRC using these strategies. We analyzed bacterial and viral communities using both DNA and RNA deep-sequencing (Novaseq) in colorectal tissue specimens from 10 CRC patients and 10 matched control patients. Following taxonomy classification using Kraken 2, different metrics for alpha and beta diversities as well as relative and differential abundance were calculated to compare tumoral and healthy samples. No viral differences were identified between tissue types, but bacterial species Polynucleobacter necessarius had a highly increased presence for DNA in tumors (p = 0.001). RNA analyses showed that bacterial species Arabia massiliensis had a highly decreased transcription in tumors (p = 0.002) while Fusobacterium nucleatum transcription was highly increased in tumors (p = 0.002). Sequencing of both DNA and RNA enables a wider perspective of micriobiome profiles. Lack of RNA transcription (Polynucleobacter necessarius) casts doubt on possible role of a microorganism in CRC. The association of F. nucleatum mainly with transcription, may provide further insights on its role in CRC. Joint assessment of the metagenome (DNA) and the metatranscriptome (RNA) at the species level provided a huge coverage for both bacteria and virus and identifies differential specific bacterial species as tumor associated.

The female upper reproductive tract harbors endogenous microbial profiles.

The female reproductive tract harbours unique microbial communities (known as microbiota) which have been associated with reproductive functions in health and disease. While endometrial microbiome studies have shown that the uterus possesses higher bacterial diversity and richness compared to the vagina, the knowledge regarding the composition of the Fallopian tubes (FT) is lacking, especially in fertile women without any underlying conditions. To address this gap, our study included 19 patients who underwent abdominal hysterectomy for benign uterine pathology, and 5 women who underwent tubal ligation as a permanent contraceptive method at Hospital Clínico Universitario Virgen de la Arrixaca (HCUVA). We analyzed the microbiome of samples collected from the FT and endometrium using 16S rRNA gene sequencing. Our findings revealed distinct microbiome profiles in the endometrial and FT samples, indicating that the upper reproductive tract harbors an endogenous microbiome. However, these two sites also shared some similarities, with 69% of the detected taxa Being common to both. Interestingly, we identified seventeen bacterial taxa exclusively present in the FT samples, including the genera Enhydrobacter, Granulicatella, Haemophilus, Rhizobium, Alistipes, and Paracoccus, among others. On the other hand, 10 bacterial taxa were only found in the endometrium, including the genera Klebsiella, Olsenella, Oscillibacter and Veillonella (FDR <0.05). Furthermore, our study highlighted the influence of the endometrial collection method on the findings. Samples obtained transcervically showed a dominance of the genus Lactobacillus, which may indicate potential vaginal contamination. In contrast, uterine samples obtained through hysterescopy revealed higher abundance of the genera Acinetobacter, Arthrobacter, Coprococcus, Methylobacterium, Prevotella, Roseburia, Staphylococcus, and Streptococcus. Although the upper reproductive tract appears to have a low microbial biomass, our results suggest that the endometrial and FT microbiome is unique to each individual. In fact, samples obtained from the same individual showed more microbial similarity between the endometrium and FT compared to samples from different women. Understanding the composition of the female upper reproductive microbiome provides valuable insights into the natural microenvironment where processes such as oocyte fertilization, embryo development and implantation occur. This knowledge can improve in vitro fertilization and embryo culture conditions for the treatment of infertility.

The relationships between microbiome diversity and epidemiology in domestic species of malaria-mediated mosquitoes of Korea

Microbiota in the mosquito plays an important role in their behavior and vector competence. The composition of their microbiome is strongly influenced by the environment, especially their habitat. The microbiome profiles of adult female Anopheles sinensis mosquitoes from malaria hyperendemic and hypoendemic areas in Republic of Korea were compared using 16S rRNA Illumina sequencing. In different epidemiology groups, the alpha and beta diversity analyses were significant. The major bacterial phylum was Proteobacteria. The most abundant species in the microbiome of hyperendemic mosquitoes were the genera Staphylococcus, Erwinia, Serratia, and Pantoea. Notably, a distinct microbiome profile characterized by the dominance of Pseudomonas synxantha was identified in the hypoendemic area, suggesting a potential correlation between the microbiome profiles and the incidence of malaria cases.

Distinct microbiome profiles in convergent wisdom tooth impactions.

Long-term retention of impacted third molars (wisdom teeth) is associated with plaque stagnation and the development of caries on the adjacent surface of the neighboring second molar. While caries and tooth loss are common outcomes of impaction, there is currently insufficient evidence to support the pre-emptive removal of asymptomatic wisdom teeth. Emerging evidence suggests that convergently growing impactions are associated with caries. We have therefore investigated the composition of dental plaque on the distal surface of the mandibular second molar at various impaction angles. We have compared the microbiome of these surfaces at four impaction angulations using short-read sequencing of the bacterial 16S rRNA gene: two convergent (horizontal and mesial) and two divergent (distal and vertical) angulations, and in cases where the wisdom tooth is missing. Horizontal angulations exhibited lower microbial diversity than mesial impactions. Amplicon Sequence Variants (ASVs) associated with Veillonella were significantly more abundant at impactions with angulations toward the midline. Using machine learning, a random forest classifier trained to distinguish microbiome profiles was used to predict the native angulations for a subset of samples, with samples from the two convergent impactions estimated with the greatest accuracy. Differences in microbial diversity were apparent between caries-associated convergent (horizontal and mesial) impacted wisdom teeth, as well as greater abundances of Veillonella ASVs at horizontal impactions.

Gastrointestinal symptoms have a minor impact on autism spectrum disorder and associations with gut microbiota and short-chain fatty acids.

Children with autism spectrum disorder (ASD) experience gastrointestinal (GI) issues more frequently and severely than children who are typically developing (TD). The connections between gastrointestinal problems, microbiota, and short-chain fatty acids (SCFAs) in ASD are still being debated. We enrolled 90 children, 45 of whom were diagnosed with ASD, and examined the impact of GI disorders on ASD. The six-item GI Severity Index questionnaire was used to evaluate gastrointestinal symptoms, while the Social Responsiveness Scale was used to evaluate autism symptoms. Further, the Children’s Sleep Habits Questionnaire and the Children’s Eating Behavior Questionnaire are used to assess sleep and eating disorders in children. We assessed fecal microbiota by 16S rRNA gene sequencing, and SCFA concentrations by gas chromatography/mass spectrometry. The results revealed that children with ASD exhibited a high rate of gastrointestinal issues (78%), as well as higher rates of social impairment and poor sleeping habits, compared to TD children. However, GI disturbances have a minor impact on autism. In addition, the levels of propionic acid, butyric acid, and valeric acid were significantly higher in the ASD group. Besides, the ASD, TD, and GI subgroups possessed distinct microbiome profiles. These findings suggest that gastrointestinal disturbances have no discernible effect on the core symptoms of autism. Although autism may not cause an increase in GI symptoms directly, alterations in metabolites, such as SCFAs, may cause GI symptoms.

Microbiome profile of soil and rhizosphere plants growing in traditional oil mining land in Wonocolo, Bojonegoro, Indonesia

Traditional oil mining poses negative effects on the environment through pollution with crude oil. One of the traditional mining sites in Wonocolo, Bojonegoro, Indonesia was reported to contaminate the surrounding area with a high level of crude oil. Therefore, this study aims to examine the microbiome profiles of contaminated soil and the rhizosphere of naturalized plants growing at the sites. It was conducted in Wonocolo, Bojonegoro to obtain an insight into the possible remediation efforts of using indigenous hydrocarbon-degrading bacteria and naturalized plants as in situ remediation agents. The results showed that the soil located close to the oil well-contained a high level of crude oil at 24.8%, and exhibited a distinct microbiome profile compared to those located further which had lower crude oil contamination of 14.15, 10.89, and 4.9%. Soil with the highest level of crude oil contamination had a comparatively higher relative abundance of assA, an anaerobic alkene-degrading gene. Meanwhile, the rhizosphere of the two naturalized plants, Muntingia calabura, and Pennisetum purpureum, exhibited indifferent microbiome profiles compared to the soil. They were found to contain less abundant hydrocarbon-degrading genes, such as C230, PAH-RHD-GP, nahAc, assA, and alkB suggesting that these naturalized plants might not be a suitable tool for in-situ remediation.

Abstract 1973: Patients with operable esophageal cancer and improved responses to combined chemoradiotherapy and immunotherapy display distinct microbiome profiles enriched in multiple Bacteroides species

Abstract Background: Preclinical and clinical data indicate that neoadjuvant chemoradiotherapy (CRT) may prime an anti-tumor immunological response in esophageal cancer driven by intratumoral CD8+ T cells and PD-L1 expression. LAG-3 is also highly expressed in esophagogastric cancers. The microbiome, a novel and potentially modifiable, biomarker of IO response, has not yet been examined in the neoadjuvant setting in esophageal cancer and is the goal of our study. Methods: Fecal samples were collected from patients with stage II/III esophageal or gastroesophageal junction carcinoma eligible for curative resection treated with the standard of care regimen of carboplatin paclitaxel (50mg/m2), radiation 50.4 Gy in 28 fractions and an Ivor-Lewis esophagectomy 6-10 weeks after last CRT and immunotherapy (IO) dose. Patients on arm A (n=11) received 2 cycles of induction with nivolumab plus 3 additional cycles on week 1, 3 and 5 of CRT. Patients on arm B (n=8) received nivolumab plus relatlimab on the same schedule (Clinical trial: NCT03044613). We examined longitudinal fecal samples from n=19 patients across both arms (n=90 samples) using 16S rRNA amplicon sequencing. Patients were classified based on pathological response: complete response (CR) and grades 1, 2, and 3 (G1, G2, G3) with increasing residual tumor visible in the resected specimen. Sequencing data was trimmed and filtered for contaminants, followed by high-resolution taxonomic assignment and normalization of reads across all samples. Analysis was performed using multiple metrics for alpha diversity and beta-diversity, with principal coordinates analysis/PERMANOVA, and pathway analysis using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Results: Patients with improved response in the neoadjuvant setting (CR/G1 vs G2/G3) grouped in distinct clusters using Bray-Curtis (p &amp;lt; 0.001). Patients with CR had higher alpha diversity, using both measures of richness and evenness, compared to patients with a G3 responses (p &amp;lt; 0.03). Specifically, family Bacteroidaceae and genus Bacteroides were enriched in patients with CR vs G3 (p &amp;lt; 0.02). At the species level, B. finegoldii, B. ovatus, and B. uniformis were enriched in patients with CR vs G3 (p &amp;lt; 0.02). In contrast, genus Klebsiella and Clostridium termitidis were enriched in patients with a poor response, G3 (p &amp;lt;0.001, both). Pathway analysis found two metabolic pathways enriched in patients with CR: secondary bile acid biosynthesis (p=0.005) and lysine biosynthesis (p=0.02). Conclusions: Patients with operable esophageal cancer and improved responses to combined CRT and IO had distinct microbiome profiles enriched in multiple Bacteroides species. Further analyses and validation efforts are underway to confirm metabolomic pathways. Citation Format: Fyza Y. Shaikh, James R. White, Ronan J. Kelly, Ali H. Zaidi, Jenna V. Canzoniero, Josephine L. Feliciano, Russell K. Hales, K Ranh Voong, Richard J. Battafarano, Blair A. Jobe, Stephen C. Yang, Stephen Broderick, Jinny Ha, Kellie N. Smith, Elizabeth Thompson, Eun J. Shin, Ali I. Amjad, Patrizia Guerrieri, Benny Weksler, Chen Hu, Valsamo Anagnostou, Vincent K. Lam, Cynthia L. Sears. Patients with operable esophageal cancer and improved responses to combined chemoradiotherapy and immunotherapy display distinct microbiome profiles enriched in multiple Bacteroides species [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1973.

Performance determinants of unsupervised clustering methods for microbiome data

BackgroundIn microbiome data analysis, unsupervised clustering is often used to identify naturally occurring clusters, which can then be assessed for associations with characteristics of interest. In this work, we systematically compared beta diversity and clustering methods commonly used in microbiome analyses. We applied these to four published datasets where highly distinct microbiome profiles could be seen between sample groups, as well a clinical dataset with less clear separation between groups.ResultsAlthough no single method outperformed the others consistently, we did identify the key scenarios where certain methods can underperform. Specifically, the Bray Curtis (BC) metric resulted in poor clustering in a dataset where high-abundance OTUs were relatively rare. In contrast, the unweighted UniFrac (UU) metric clustered poorly on dataset with a high prevalence of low-abundance OTUs. To explore these hypotheses about BC and UU, we systematically modified the properties of the poorly performing datasets and found that this approach resulted in improved BC and UU performance. Based on these observations, we rationally combined BC and UU to generate a novel metric. We tested its performance while varying the relative contributions of each metric and also compared it with another combined metric, the generalized UniFrac distance. The proposed metric showed high performance across all datasets.ConclusionsOur systematic evaluation of clustering performance in these five datasets demonstrates that there is no existing clustering method that universally performs best across all datasets. We propose a combined metric of BC and UU that capitalizes on the complementary strengths of the two metrics.syUurMUnqpLuEn-KfNXmwVideo abstract

Microorganism Profiles of Penile Prosthesis Removed for Infection, Erosion, and Mechanical Malfunction Based on Next-Generation Sequencing

Next-generation sequencing (NGS) is an emerging technology that may allow for more sensitive and sophisticated microbial testing of the microbiota of penile prostheses (PP). To describe the microorganism profiles of PP explanted for infection, erosion, and mechanical malfunction using NGS. All patients who underwent PP removal by two physicians at two institutions were identified. Differences in alpha diversity (ie, number of species detected, species diversity across samples) and microbiome compositional profiles (Bray-Curtis community dissimilarities) across samples were assessed using ANOVA and PERMANOVA, respectively. Number of species detected, species diversity across samples, and microbiome compositional profiles. A total of 83 patients who underwent device removal for infection (n = 8, 10%), erosion (n = 5, 6%), and mechanical malfunction (n = 70, 84%) were included. When considering all devices, 56% (n = 48) of NGS and 29% (n = 24) of standard cultures resulted positive for presence of microorganisms. Culture only detected the most abundant NGS species in 62.5% (n = 5) of infected devices. Species richness and microbiome compositional profiles varied by surgical indication, but not by age, race, diabetes status, or implant duration. Most frequent organisms by surgical indication were Pseudomonas aeruginosa (infection), Staphylococcus epidermidis (erosion), and Escherichia coli (mechanical malfunction). The highest relative abundance organisms were P aeruginosa (infection), Corynebacterium jeikeium (erosion), and E coli (mechanical malfunction). Identifying microbiome profiles of PP removed for infection, erosion, and mechanical malfunction may guide the selection of peri-operative antibiotics and PP antibiotic coatings or hydrophilic dip solutions for each individual scenario. While this is the first study to utilize next-generation sequencing to evaluate penile prosthesis biofilm, the clinical significance of these findings has yet to be determined. A prospective, randomized trial aimed at evaluating the clinical significance of NGS in patients with PP infection is currently underway. NGS testing identified distinct microbiome profiles of PP removed for infection, erosion, and mechanical malfunction.

Distinct microbiome profiles and biofilms in Leishmania donovani-driven cutaneous leishmaniasis wounds

The endemic strain of Leishmania donovani in Sri Lanka causes cutaneous leishmaniasis (CL) rather than more common visceral form. We have visualized biofilms and profiled the microbiome of lesions and unaffected skin in thirty-nine CL patients. Twenty-four lesions (61.5%) were biofilm-positive according to fluorescence in situ hybridization. Biopsies of biofilm-positive lesions were dominated by Pseudomonas, class Bacilli and Enterobacteriaceae and distinguished by significantly lower community evenness. Higher relative abundance of a class Bacilli OTU was detected in wound swabs versus contralateral skin. Wound swabs and biopsies had significantly distinct microbiome profiles and lower diversity compared to unaffected skin. Greater abundances of potentially pathogenic organisms were observed in wet ulcers, lesions with high parasite loads and large wounds. In summary, more than half of L. donovani associated CL wounds harboured biofilms and the wounds exhibited a distinct, less diverse, microbiome than unaffected skin.

Characterization of the Genitourinary Microbiome of 1,165 Middle-Aged and Elderly Healthy Individuals.

Accumulated evidence shows that complex microbial communities resides in the healthy human urinary tract and can change in urological disorders. However, there lacks a comprehensive profiling of the genitourinary microbiota in healthy cohort. Here, we performed 16S rRNA gene sequencing of midstream urine specimens from 1,172 middle-aged and elderly healthy individuals. The core microbiota included 6 dominant genera (mean relative abundance >5%), including Prevotella, Streptococcus, Lactobacillus, Gardnerella, Escherichia-Shigella, and Veillonella, and 131 low-abundance genera (0.01–5%), displaying a distinct microbiome profiles to that of host-matched gut microbiota. The composition and diversity of genitourinary microbiome (GM) were distinct between genders and may fluctuate with ages. Several urotypes were identified by the stratification of microbiome profiles, which were mainly dominated by the six most predominant genera. The prevalence of urotypes was disparate between genders, and the male sample additionally harbored other urotypes dominated by Acinetobacter, Corynebacterium, Staphylococcus, or Sphingomonas. Peptoniphilus, Ezakiella, and Porphyromonas were co-occurred and co-abundant, and they may play crucial roles as keystone genera and be associated with increased microbial diversity. Our results delineated the microbial structure and diversity landscape of the GM in healthy middle-aged and elderly adults and provided insights into the influence of gender and age to it.

Dose-Dependent Effects of Dietary Xylooligosaccharides Supplementation on Microbiota, Fermentation and Metabolism in Healthy Adult Cats.

In order to investigate the effect and appropriate dose of prebiotics, this study evaluated the effect of two levels of xylooligosaccharides (XOS) in cats. Twenty-four healthy adult cats were divided into three groups: no-XOS control diet with 1% cellulose; low XOS supplementation (LXOS) with 0.04% XOS and 0.96% cellulose; and high XOS supplementation (HXOS) with 0.40% XOS and 0.60% cellulose. Both XOS groups increased blood 3-hydroxybutyryl carnitine levels and decreased hexadecanedioyl carnitine levels. Both XOS treatments displayed an increased bacterial abundance of Blautia, Clostridium XI, and Collinsella and a decreased abundance of Megasphaera and Bifidobacterium. LXOS groups increased fecal pH and bacterial abundance of Streptococcus and Lactobacillus, decreased blood glutaryl carnitine concentration, and Catenibacterium abundance. HXOS group showed a more distinct microbiome profile and higher species richness, and an increased bacterial abundance of Subdoligranulum, Ruminococcaceae genus (unassigned genus), Erysipelotrichaceae genus, and Lachnospiraceae. Correlations between bacterial abundances and blood and fecal parameters were also observed. In conclusion, XOS could benefit feline gut health by altering microbiota; its effects dependant on the dose. The higher-dose XOS increased bacterial populations that possibly promoted intestinal fermentation, while the lower dose altered populations of carbohydrate-metabolic microbiota and possibly modulated host metabolism. Low-dose prebiotics may become a trend in future studies.

Gastric microbiota and Helicobacter pylori in Indonesian population.

The profile of gastric mucosal microbiota has not yet been described in the Indonesian population where the prevalence of Helicobacter pylori is low. This is a cross-sectional study analyzing 16S rRNA of 137 gastric biopsy specimens. We analyzed the association between gastric microbiota, H. pylori infection, and gastric mucosal damage. Among 137 analyzed samples, 27 were H. pylori-positive and 110 were H. pylori -negative based on culture, histology, and 16S rRNA gene analysis. Significantly lower α-diversity parameters, including Pielou's index, was observed in H. pylori-infected individuals compared with noninfected individuals (all P<.001). Among H. pylori-negative individuals, the permutational analysis of variance of Bray-Curtis dissimilarity distances showed a significant association with different ethnicities, suggesting some ethnic groups had specific microbiota profiles based on the presence of different operational taxonomic units. The linear discriminant analysis effect size (LEfSe) of the H. pylori-negative group showed significant associations between the presence of Micrococcus luteus and Sphingomonas yabuuchiae with Timor and Papuan ethnicities, respectively. The presence of Bulledia sp and Atopobium sp was associated with the Javanese ethnicity. We observed lower α-diversity scores in individuals with gastric mucosal damage and profiles with high abundances of Paludibacter sp and Dialister sp based on LEfSe analysis. Our findings suggest the presence of H. pylori is more correlated with a distinct microbiome profile than ethnic precedence.

Baseline microbiota composition modulates antibiotic-mediated effects on the gut microbiota and host

BackgroundNormal mammalian development and homeostasis are dependent upon the gut microbiota. Antibiotics, essential for the treatment and prophylaxis of bacterial infections, can have collateral effects on the gut microbiota composition, which can in turn have far-reaching and potentially deleterious consequences for the host. However, the magnitude and duration of such collateral effects appear to vary between individuals. Furthermore, the degree to which such perturbations affect the host response is currently unclear. We aimed to test the hypothesis that different human microbiomes have different responses to a commonly prescribed antibiotic and that these differences may impact the host response.MethodsGerm-free mice (n = 30) humanized with the microbiota of two unrelated donors (A and B) were subjected to a 7-day antibiotic challenge with amoxicillin-clavulanate (“co-amoxiclav”). Microbiome and colonic transcriptome analysis was performed, pre (day 0) and post antibiotics (day 8) and subsequently into recovery (days 11 and 18).ResultsUnique community profiles were evident depending upon the donor, with donor A recipient mice being dominated by Prevotella and Faecalibacterium and donor B recipient mice dominated by Bacteroides and Parabacteroides. Donor A mice underwent a marked destabilization of their microbiota following antibiotic treatment, while donor B mice maintained a more stable profile. Dramatic and overlapping alterations in the host transcriptome were apparent following antibiotic challenge in both groups. Despite this overlap, donor A mice experienced a more significant alteration in gene expression and uniquely showed correlations between host pathways and key microbial genera.ConclusionsGerm-free mice humanized by different donor microbiotas maintain distinct microbiome profiles, which respond in distinct ways to antibiotic challenge and evince host responses that parallel microbiome disequilibrium. These results suggest that inter-individual variation in the gut microbiota may contribute to personalized host responses following microbiota perturbation.

Modification of the gut microbiome to combat neurodegeneration

The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.

Role of Gut Microbiota and Immunity in the Dietary Modulation of Dahl Salt‐Sensitive Hypertension

Studies from our laboratory have demonstrated that immune cells infiltrate the kidneys and amplify the hypertension and renal damage observed in Dahl Salt‐Sensitive (SS) rats when fed 4.0% high salt (HS). These rats are bred at the Medical College of Wisconsin (SS/MCW) and are maintained on a highly purified, casein‐based diet. Interestingly, SS rats fed a whole grain diet (SS/CRL) or modified wheat gluten diet (SS/WG) have drastically reduced salt‐induced hypertension, albuminuria, and renal inflammation compared to the casein‐fed SS/MCW. With the linkage of the gut microbial composition to many of the risk factors associated with hypertension, the current study sought to define the Dahl SS gut microbiome in the presence of these dietary modulations and to test the hypothesis that gut bacteria directly contribute to the development of hypertension and renal disease. Fecal 16S rRNA sequencing revealed distinct microbiome profiles between SS/MCW, SS/CRL, and SS/WG, with significant shifts in gut microbiome composition due to age, salt, and sex (n=4–6). Furthermore, there were families of salt responsive bacteria that, depending on the diet of the group, became specifically enriched (Ruminococcaceae, Clostridiaceae, Prevotellaceae) or depleted (Lachnospiraceae) after 3 weeks of HS. To assess the direct contribution of gut bacteria to the development of SS hypertension, we treated SS/MCW rats with a broad‐spectrum antibiotic cocktail of bacitracin and streptomycin (Bac/Strep, 2 g/L in drinking water). Bac/Strep treatment resulted in a significant reduction in mean arterial pressure (167.3±5.0 vs 148.9±3.0 mmHg, Vehicle vs Bac/Strep, n=6–8, p&lt;0.001) and albuminuria (221.5±34.3 vs 130.2±16.2 mg/day, p&lt;0.05) compared to vehicletreated rats, suggesting that Bac/Strep treatment eliminated certain gut bacteria responsible for driving the phenotype in Dahl SS rats. As further proof of principle, SS/CRL recipient rats were administered daily fecal microbiota transfer (FMT, 0.1g stool/day) from SS/MCW donor rats starting at 6 weeks of age and throughout the HS period starting at 9 weeks of age. These transfer experiments of the SS/MCW microbiota into SS/CRL rats worsened renal disease progression by increasing both proteinuria (148.0±15.0 vs 209.4±39.8 mg/day, Vehicle vs SS/MCW FMT, n=5, p&lt;0.05) and albuminuria (67.3±6.9 vs 113.7±25.0 mg/day, p&lt;0.01), which also coincided with an increase in systolic arterial pressure (158.6±5.8 vs 177.8±8.9 mmHg, p=0.09). Upon analysis of the immune cells in the kidneys of the SS/MCW FMT, there was a specific increase in the number of CD4+ T helper cells (1.7‐fold, p&lt;0.05) and CD8+ cytotoxic T cells (2.0‐fold, p&lt;0.05), with no differences observed in the number of CD11b/c+ monocytes/macrophages or CD45R+ B cells. While the specific mechanisms linking gut dysbiosis to the SS hypertensive, renal injury, and renal inflammatory phenotype are still under current investigation, our present data excitingly demonstrate that the dietary modulation of gut bacteria are directly contributing to the development and progression of the Dahl SS phenotype.Support or Funding InformationHL116264, HL137748, 15SFRN2391002This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.