Changes In Microbial Composition Research Articles

A novel combinatorial approach usingsulforaphane- and withaferin A-rich extracts for prevention of estrogen receptor-negative breast cancer through epigenetic and gut microbial mechanisms.

Estrogen receptor-negative [ER(-)] mammary cancer is the most aggressive type of breast cancer (BC) with higher rate of metastasis and recurrence. In recent years, dietary prevention of BC with epigenetically active phytochemicals has received increased attention due to its feasibility, effectiveness, and ease of implementation. In this regard, combinatorial phytochemical intervention enables more efficacious BC inhibition by simultaneously targeting multiple tumorigenic pathways. We, therefore, focused on investigation of the effect of sulforaphane (SFN)-rich broccoli sprouts (BSp) and withaferin A (WA)-rich Ashwagandha (Ash) combination on BC prevention in estrogen receptor-negative [ER(-)] mammary cancer using transgenic mice. Our results indicated that combinatorial BSp + Ash treatment significantly reduced tumor incidence and tumor growth (~ 75%) as well as delayed (~ 21%) tumor latency when compared to the control treatment and combinatorial BSp + Ash treatment was statistically more effective in suppressing BC compared to single BSp or Ash intervention. At the molecular level, the BSp and Ash combination upregulated tumor suppressors (p53, p57) along with apoptosis associated proteins (BAX, PUMA) and BAX:BCL-2 ratio. Furthermore, our result indicated an expressional decline of epigenetic machinery HDAC1 and DNMT3A in mammary tumor tissue because of combinatorial treatment. Interestingly, we have reported multiple synergistic interactions between BSp and Ash that have impacted both tumor phenotype and molecular expression due to combinatorial BSp and Ash treatment. Our RNA-seq analysis results also demonstrated a transcriptome-wide expressional reshuffling of genes associated with multiple cell-signaling pathways, transcription factor activity and epigenetic regulations due to combined BSp and Ash administration. In addition, we discovered an alteration of gut microbial composition change because of combinatorial treatment. Overall, combinatorial BSp and Ash supplementation can prevent ER(-) BC through enhanced tumor suppression, apoptosis induction and transcriptome-wide reshuffling of gene expression possibly influencing multiple cell signaling pathways, epigenetic regulation and reshaping gut microbiota.

Bidirectional communication of the gut-brain axis: new findings in Parkinson’s disease and inflammatory bowel disease

Parkinson’s disease (PD) and inflammatory bowel disease (IBD) are the two chronic inflammatory diseases that are increasingly affecting millions of people worldwide, posing a major challenge to public health. PD and IBD show similarities in epidemiology, genetics, immune response, and gut microbiota. Here, we review the pathophysiology of these two diseases, including genetic factors, immune system imbalance, changes in gut microbial composition, and the effects of microbial metabolites (especially short-chain fatty acids). We elaborate on the gut–brain axis, focusing on role of gut microbiota in the pathogenesis of PD and IBD. In addition, we discuss several therapeutic strategies, including drug therapy, fecal microbiota transplantation, and probiotic supplementation, and their potential benefits in regulating intestinal microecology and relieving disease symptoms. Our analysis will provide a new understanding and scientific basis for the development of more effective therapeutic strategies for these diseases.

Changes in chemical properties and microbial communities' composition of a forest litter-based biofertilizer produced through aerated solid-state culture under different oxygen conditions.

Fermented forest litter (FFL) is a bioproduct used as biofertilizer for several decades in Eastern Asia and Latin America. It is locally handcrafted by farmers in anaerobic conditions by fermenting forest litter added with agricultural by-products such as whey, cereal bran, and molasses. The aim of this study was to characterize the FFL process and product through gas and liquid chromatography analyses. It also provides some highlights on the influence of O2 on this solid-state culture. Under anoxic condition, a maximum CO2 production rate (CDPR) of 0.41mL/h∙g dry matter (dm) was reached after 8days. The main volatile organic compounds (VOCs) were ethanol and ethyl acetate, with a production rate profile similar to CDPR. After 21days of culture, no residual sucrose nor lactose was detected. Lactic and acetic acids reached 58.8mg/g dm and 10.2mg/g dm, respectively, ensuring the acidification of the matrix to a final pH of 4.72. A metabarcoding analysis revealed that heterolactic acid bacteria (Lentilactobacillus, Leuconostoc), homolactic acid bacteria (Lactococcus), and yeasts (Saccharomyces, Clavispora) were predominant. Predicted genes in the microbiome confirmed the potential link between detected bacteria and acids and VOCs produced. When O2 was fed to the cultures, final pH reached values up to 8.5. No significant amounts of lactic nor acetic acid were found. In addition, a strong shift in microbial communities was observed, with a predominance of Proteobacteria and molds, among which are potential pathogens like Fusarium species. This suggests that particular care must be brought to maintain anoxic conditions throughout the process.

Metagenomic sequencing and reconstruction of 82 microbial genomes from barley seed communities

Barley (Hordeum vulgare) is essential to global food systems and the brewing industry. Its physiological traits and microbial communities determine malt quality. Although microbes influence barley from seed health to fermentation, there is a gap in metagenomic insights during seed storage. Crucially, elucidating the changes in microbial composition associated with barley seeds is imperative for understanding how these fluctuations can impact seed health and ultimately, influence both agricultural yield and quality of barley-derived products. Whole metagenomes were sequenced from eight barley seed samples obtained at different storage time points from harvest to nine months. After binning, 82 metagenome-assembled genomes (MAGs) belonging to 26 distinct bacterial genera were assembled, with a substantial proportion of potential novel species. Most of our MAG dataset (61%) showed over 90% genome completeness. This pioneering barley seed microbial genome retrieval provides insights into species diversity and structure, laying the groundwork for understanding barley seed microbiome interactions at the genome level.

Effects of denitrification on speciation and redistribution of arsenic in estuarine sediments

Microbially-mediated redox processes involving arsenic (As) and its host minerals significantly contribute to the mobilization of As in estuarine sediments. Despite its significance, the coupling between As dynamics and denitrification processes in these sediments is not well understood. This study employed sequential sediment extractions and simultaneous monitoring of dissolved iron (Fe), nitrogen (N), and sulfur (S) to investigate the impact of nitrate (NO3−) on the speciation and redistribution of As, alongside changes in microbial community composition. Our results indicated that NO3− additions significantly enhance anaerobic arsenite (As(III)) oxidation, facilitating its immobilization by increased adsorption onto sediment matrices in As-contaminated estuarine settings. Furthermore, NO3− promoted the conversion of As bound to troilite (FeS) and pyrite (FeS2) into forms associated with Fe oxides, challenging the previously assumed stability of FeS/FeS2-bound As in such environments. Continuous NO3− additions ensured As and Fe oxidation, thereby preventing their reductive dissolution and stabilizing the process that reduces As mobility. Changes in the abundance of bacterial communities and correlation analyses revealed that uncultured Anaerolineaceae and Thioalkalispira may be the main genus involved in these transformations. This study underscores the critical role of NO3− availability in modulating the biogeochemical cycle of As in estuarine sediments, offering profound insights for enhancing As immobilization techniques and informing environmental management and remediation strategies in As-contaminated coastal regions.

Diet-omics in the Study of Urban and Rural Crohn disease Evolution (SOURCE) cohort

Crohn disease (CD) burden has increased with globalization/urbanization, and the rapid rise is attributed to environmental changes rather than genetic drift. The Study Of Urban and Rural CD Evolution (SOURCE, n = 380) has considered diet-omics domains simultaneously to detect complex interactions and identify potential beneficial and pathogenic factors linked with rural-urban transition and CD. We characterize exposures, diet, ileal transcriptomics, metabolomics, and microbiome in newly diagnosed CD patients and controls in rural and urban China and Israel. We show that time spent by rural residents in urban environments is linked with changes in gut microbial composition and metabolomics, which mirror those seen in CD. Ileal transcriptomics highlights personal metabolic and immune gene expression modules, that are directly linked to potential protective dietary exposures (coffee, manganese, vitamin D), fecal metabolites, and the microbiome. Bacteria-associated metabolites are primarily linked with host immune modules, whereas diet-linked metabolites are associated with host epithelial metabolic functions.

Structure and composition of microbial communities in the water column from Southern Gulf of Mexico and detection of putative hydrocarbon-degrading microorganisms.

This study assessed the bacterioplankton community and its relationship with environmental variables, including total petroleum hydrocarbon (TPH) concentration, in the Yucatan shelf area of the Southern Gulf of Mexico. Beta diversity analyses based on 16S rRNA sequences indicated variations in the bacterioplankton community structure among sampling sites. PERMANOVA indicated that these variations could be mainly related to changes in depth (5 to 180 m), dissolved oxygen concentration (2.06 to 5.93 mg L-1), and chlorophyll-a concentration (0.184 to 7.65 mg m3). Moreover, SIMPER and one-way ANOVA analyses showed that the shifts in the relative abundances of Synechococcus and Prochlorococcus were related to changes in microbial community composition and chlorophyll-a values. Despite the low TPH content measured in the studied sites (0.01 to 0.86 μL L-1), putative hydrocarbon-degrading bacteria such as Alteromonas, Acinetobacter, Balneola, Erythrobacter, Oleibacter, Roseibacillus, and the MWH-UniP1 aquatic group were detected. The relatively high copy number of the alkB gene detected in the water column by qPCR and the enrichment of hydrocarbon-degrading bacteria obtained during lab crude oil tests exhibited the potential of bacterioplankton communities from the Yucatan shelf to respond to potential hydrocarbon impacts in this important area of the Gulf Mexico.

Magnolia Officinalis Alcohol Extract Alleviates the Intestinal Injury Induced by Polygala Tenuifolia Through Regulating the PI3K/AKT/NF-κB Signaling Pathway and Intestinal Flora.

Polygala tenuifolia Willd. (PT), a traditional Chinese medicinal plant extensively employed in managing Alzheimer's disease, exhibits notable gastrointestinal side effects as highlighted by prior investigations. In contrast, Magnolia officinalis Rehd. et Wils (MO), a traditional remedy for gastrointestinal ailments, shows promising potential for ameliorating this adverse effect of PT. The objective of this study is to examine the underlying mechanism of MO in alleviating the side effects of PT. Hematoxylin-eosin (H&E) staining was used to observe the structural damage of zebrafish intestine, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors and oxidative stress. The integrity of the intestinal tight junctions was examined using transmission electron microscope (TEM). Moreover, the expression of intestinal barrier genes and PI3K/AKT/NF-κB signaling pathway-related genes was determined through quantitative real-time PCR. The changes in intestinal microbial composition were analyzed using 16S rRNA and metagenomic techniques. MO effectively ameliorated intestinal pathological damage and barrier gene expression, and significantly alleviated intestinal injury by reducing the expression of inflammatory cytokines IL-1β, IL-6, TNF-α, and inhibiting the activation of PI3K/AKT/NF-κB pathway. Furthermore, MO could significantly increase the relative abundance of beneficial microorganisms (Lactobacillus, Blautia and Saccharomyces cerevisiae), and reduce the relative abundance of pathogenic bacteria (Plesiomonas and Aeromonas). MO alleviated PT-induced intestinal injury, and its mechanism may be related to the inhibition of PI3K/AKT/NF-κB pathway activation and regulation of intestinal flora.

Spontaneous fermentation mitigates the frequency of genes encoding antimicrobial resistance spreading from the phyllosphere reservoir to the diet

The phyllosphere microbiome of vegetable products constitutes an important reservoir for multidrug resistant bacteria and Antibiotic Resistance Genes (ARG). Vegetable products including fermented products such as Paocai therefore may serve as a shuttle for extrinsic microorganisms with ARGs into the gut of consumers. Here we study the effect of fermentation on Paocai ARG dissemination by metagenomic analysis. Microbial abundance and diversity of the Paocai microbiome were diminished during fermentation, which correlated with the reduction of abundance in ARGs. Specifically, as fermentation progressed, Enterobacterales overtook Pseudomonadales as the predominant ARG carriers, and Lactobacillales and Enterobacteriales became the determinants of Paocai resistome variation. Moreover, the dual effect of microbes and metal resistance genes (MRGs) was the major contributor driving Paocai resistome dynamics. We recovered several metagenome-assembled genomes (MAGs) carrying acquired ARGs in the phyllosphere microbiome. ARGs of potential clinical and epidemiological relevance such as tet M and emrB-qacA, were mainly hosted by non-dominant bacterial genera. Overall, our study provides evidence that changes in microbial community composition by fermentation aid in constraining ARG dispersal from raw ingredients to the human microbiome but does not eliminate them.

Treatment for Rheumatoid Arthritis Associated With Alterations in the Gastrointestinal Microbiota.

Emerging research suggests that rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This prospective pilot study evaluates changes in intestinal microbial composition in patients with RA initiating treatment with either methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi). Consecutive patients, fulfilling the 2010 American College of Rheumatology/EULAR classification criteria for RA, who started treatment with either MTX or TNFi delivered a stool sample upon initiation of immunosuppression and 3 months later. A 16S ribosomal RNA gene-based validated microbiota test (GA-map Dysbiosis Index Score [DIS], Genetic Analysis, Oslo, Norway) was used to evaluate for the presence and degree of dysbiosis. Fecal levels of Prevotella copri (P. copri) were analyzed by custom-made quantitative polymerase chain reaction. Changes in microbial composition were analyzed in relation to changes in disease activity, as measured by the disease activity score based on 28-joint counts, using C-reactive protein. At baseline, dysbiosis was present in 33 of 50 (66%) participants and more common in participants with more than 2 years of disease duration (P = 0.019). At the 3-month follow-up, 27 of 50 (54%) were good treatment responders and the DIS had improved in 14 of 50 (28%). Participants initiating TNFi more often exhibited improvement in the DIS compared with those initiating MTX (P = 0.031). P. copri was identified in 32 of 50 (64%) at baseline. An improvement in disease activity score based on 28-joint counts, using C-reactive protein was associated with a simultaneous decrease in P. copri abundance (rs = 0.30, P = 0.036). This study affirms that dysbiosis is a feature of RA. Although patients were not randomized to MTX or TNFi, the findings suggest that specific therapies may differentially modulate the gastrointestinal microbiota in RA. The association between P. copri and treatment response requires further study.

Changes in microbial composition explain the contrasting responses of glucose and lignin decomposition to soil acidification in an alpine grassland

Soil acidification often suppresses microbial growth and activities, resulting in a negative impact on soil organic carbon (C) decomposition. While the detrimental effects of acidification on soil and plant properties have been extensively studied, less attention has been paid on the shifts in soil microbial communities and their influences of the decomposition of organic C with different chemical complexities. Taking advantage of an acid addition experiment in a Tibetan alpine meadow, here we examined the response of soil microbial communities to soil acidification and microbial effect on the decomposition of organic C with different chemical complexities (i.e., glucose and lignin, representing labile and recalcitrant C respectively). We found that soil acidification had no impact on microbial respiration and microbial abundance even though it decreased bacterial diversity significantly. Soil acidification increased the relative abundance of some microbial taxa, like Alphaproteobacteria and Acidobacteriia in bacteria increased by 36 %, 284 %, and Eurotiomycetes, Sordariomycetes and Leotiomycetes in fungi increased by 145 %, 279 % and 12.7-fold, but decreased the relative abundance of Acidimicrobiia by 33 % in highest acid addition treatment. Changes in microbial communities (bacterial and fungal community composition, the diversity of bacterial community and the ratio of fungi to bacteria) are significantly related to the decomposition of glucose and lignin. More specifically, soil acidification decreased the decomposition of glucose but increased the decomposition of lignin, indicating a trade-off between the decomposition of labile and recalcitrant soil organic C under soil acidification. Overall, shifts in microbial communities under soil acidification might be accompanied by an increased ability to break down more recalcitrant C. This trade-off between the decomposition of labile and recalcitrant C may change soil C quality under future acid deposition scenarios.

Metagenomic and transcriptomic analysis revealing the impact of oxytetracycline and ciprofloxacin on gut microbiota and gene expression in the Chinese giant salamander (Andrias davidianus)

Excessive antibiotic use has led to the spread of antibiotic resistance genes (ARGs), impacting gut microbiota and host health. However, the effects of antibiotics on amphibian populations remain unclear. We investigated the impact of oxytetracycline (OTC) and ciprofloxacin (CIP) on Chinese giant salamanders (Andrias davidianus), focusing on gut microbiota, ARGs, and gene expression by performing metagenome and transcriptome sequencing. A. davidianus were given OTC (20 or 40 mg/kg) or CIP (50 or 100 mg/kg) orally for 7 days. The results revealed that oral administration of OTC and CIP led to distinct changes in microbial composition and functional potential, with CIP treatment having a greater impact than OTC. Antibiotic treatment also influenced the abundance of ARGs, with an increase in fluoroquinolone and multi-drug resistance genes observed post-treatment. The construction of metagenome-assembled genomes (MAGs) accurately validated that CIP intervention enriched fish-associated potential pathogens Aeromonas hydrophila carrying an increased number of ARGs. Additionally, mobile genetic elements (MGEs), such as phages and plasmids, were implicated in the dissemination of ARGs. Transcriptomic analysis of the gut revealed significant alterations in gene expression, particularly in immune-related pathways, with differential effects observed between OTC and CIP treatments. Integration of metagenomic and transcriptomic data highlighted potential correlations between gut gene expression and microbial composition, suggesting complex interactions between the host gut and its gut microbiota in response to antibiotic exposure. These findings underscore the importance of understanding the impact of antibiotic intervention on the gut microbiome and host health in amphibians, particularly in the context of antibiotic resistance and immune function.

The Diversity and Composition of Soil Microbial Communities Differ in Three Land Use Types of the Sanjiang Plain, Northeastern China.

In recent years, the Sanjiang Plain has experienced drastic human activities, which have dramatically changed its ecological environment. Soil microorganisms can sensitively respond to changes in soil quality as well as ecosystem function. In this study, we investigated the changes in soil microbial community diversity and composition of three typical land use types (forest, wetland and cropland) in the Sanjiang Plain using phospholipid fatty acid analysis (PLFA) technology, and 114 different PLFA compounds were identified. The results showed that the soil physicochemical properties changed significantly (p < 0.05) among the different land use types; the microbial diversity and abundance in cropland soil were lower than those of the other two land use types. Soil pH, soil water content, total organic carbon and available nitrogen were the main soil physico-chemical properties driving the composition of the soil microbial community. Our results indicate that the soil microbial community response to the three different habitats is complex, and provide ideas for the mechanism by which land use changes in the Sanjiang Plain affect the structure of soil microbial communities, as well as a theoretical basis for the future management and sustainable use of the Sanjiang plain, in the northeast of China.

Effect of aerobic exercise and particulate matter exposure duration on the diversity of gut microbiota

ABSTRACT Inhalation of ambient particulate matter (PM) can disrupt the gut microbiome, while exercise independently influences the gut microbiome by promoting beneficial bacteria. In this study, we analyzed changes in gut microbial diversity and composition in response to combined interventions of PM exposure and aerobic exercise, extending up to 12 weeks. This investigation was conducted using mice, categorized into five groups: control group (Con), exercise group (EXE), exercise group followed by 3-day exposure to PM (EXE + 3-day PM), particulate matter exposure (PM), and PM exposure with concurrent treadmill exercise (PME). Notably, the PM group exhibited markedly lower alpha diversity and richness compared to the Con group and our analysis of beta diversity revealed significant variations among the intervention groups. Members of the Lachnospiraceae family showed significant enhancement in the exercise intervention groups (EXE and PME) compared to the Con and PM groups. The biomarker Lactobacillus, Coriobacteraceae, and Anaerofustis were enriched in the EXE group, while Desulfovibrionaceae, Mucispirillum schaedleri, Lactococcus and Anaeroplasma were highly enriched in the PM group. Differential abundance analysis revealed that Paraprevotella, Bacteroides, and Blautia were less abundant in the 12-week PM exposure group than in the 3-day PM exposure group. Moreover, both the 3-day and 12-week PM exposure groups exhibited a reduced relative abundance of Bacteroides uniformis, SMB53, and Staphylococcus compared to non-PM exposure groups. These findings will help delineate the possible roles and associations of altered microbiota resulting from the studied interventions, paving the way for future mechanistic research.

The Effects of Mine Waste and Rain Water on the Structure of Bacteria Community of Paddy Soils

ABSTRACT Heavy metal contamination of soil has become one of the most important environmental problems worldwide. Heavy metals can affect growth and lead to changes in microbial community composition, which could influence the growth of crops in the soil. In this study, we conducted an experiment to investigate the distribution profile of heavy metals and bacterial communities in soil with the effects of slag and/or water on the top of the soil. Extra heavy metals, acting as selective pressure, led to the loss of sensitive taxa, with tolerant or less sensitive taxa being more abundant in the community. The results showed that the addition of slag on the top of soils did not change the diversity of bacteria but influenced the relative abundance of indigenous members in the community. Water addition, however, improved the homogeneity of the environment vertically in the soil, which consequently led to a lower variation in the bacterial community. This study mimicked the scenario of tailings and abandoned mines in nature, and aimed to study the effects of mines on the soil microbial community with the influence of precipitation on the distribution of heavy metals in the soil. With the effect of precipitation, the transportation of heavy metals in the slag may influence the local bacterial community and subsequently undermine the quality of soil for agriculture. These observations provide evidence of the effects of heavy metals on the soil around abandoned mines without any treatment. Mining causes both heavy metal and water pollution, which may lead to the accumulation of heavy metals in plants and agricultural production. Therefore, it is necessary to take care of tailings with proper procedures instead of exposing them to nature.

Improvement mechanism of volatile flavor in fermented tilapia surimi by cooperative fermentation of Pediococcus acidilactici and Latilactobacillus sakei: Quantization of microbial contribution through influence of genus

Single starter can hardly improve the volatile flavor of fermented fish surimi. In this study, the changes of volatile compounds (VCs) and microbial composition during cooperative fermentation of Latilactobacillus sakei and Pediococcus acidilactici were studied by headspace solid-phase microextraction gas chromatography–mass spectrometry and 16S rRNA gene high-throughput sequencing. During cooperative fermentation, most VCs and the abundance of Latilactobacillus and Lactococcus significantly increased, while Pediococcus, Acinetobacter, and Macrococcus obviously decreased. After evaluation of correlation and abundance of each genus, Latilactobacillus and Lactococcus possessed the highest influence on the formation of volatile flavor during cooperative fermentation. Compared with the natural fermentation, cooperative fermentation with starters significantly enhanced most of pleasant core VCs (odor activity value≥1), but inhibited the production of trimethylamine and methanethiol, mainly resulting from the absolutely highest influence of Latilactobacillus. Cooperative fermentation of starters is an effective method to improve the volatile flavor in the fermented tilapia surimi.

Changes and driving factors of microbial community composition and functional groups during the decomposition of Pinus massoniana deadwood.

Clarifying changes in the microbial community in deadwood at different stages of decomposition is crucial for comprehending the role of deadwood in the biogeochemical processes and the sustainability of forest development. However, there have been no reports on the dynamics of microbial community during the decomposition of Pinus massoniana. We used the "space-for-time" substitution to analyze the characteristics of microbial community changes and the key influencing factors in the P. massoniana deadwood during different decomposition stages by 16S and ITS rRNA gene sequencing. The results suggest that the microbial community structure of the early decomposition (decay class I) was significantly different from the other decay classes, while the diversity and richness of the microbial community were the highest in the late decomposition (decay class V). The Linear Discriminant Analysis Effect Size analysis revealed that most bacterial and fungal taxa were significantly enriched in decay classes I and V deadwood. During the initial stages of decomposition, the relative abundance of the bacterial functional group responsible for carbohydrate metabolism was greater than the later stages. As decomposition progressed, the relative abundance of saprophytic fungi gradually decreased, and there was a shift in the comparative abundance of mixed saprophytic-symbiotic fungi from low to high before eventually decreasing. Total organic carbon, total nitrogen, carbon-to-nitrogen ratio, total potassium, total phenol, condensed tannin, lignin, and cellulose were significantly correlated with microbial community structure, with the carbon-to-nitrogen ratio having the greatest effect. Our results indicate that the physicochemical properties of deadwood, microbial community structural composition and functional group changes were related to the decay class, among which the carbon-to-nitrogen ratio may be an important factor affecting the composition and diversity of microbial communities.

Alterations in Gut Microbiota and Their Correlation with Brain Beta-Amyloid Burden Measured by 18F-Florbetaben PET in Mild Cognitive Impairment Due to Alzheimer's Disease.

(1) Background: This study investigated changes in the gut microbial composition of individuals with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) and their relationship with positron emission tomography (PET) amyloid accumulation. (2) Methods: In total, 17 cognitively normal individuals without amyloid-beta (Aβ) accumulation (Aβ-NC) and 24 with Aβ-positive mild cognitive impairment (Aβ+MCI) who underwent 18F-florbetaben PET and fecal bacterial 16S ribosomal RNA gene sequencing were enrolled. The taxonomic compositions of the Aβ-NC and Aβ+MCI groups were compared. The abundance of taxa was correlated with the standardized uptake value ratio (SUVR), using generalized linear models. (3) Results: There were significant differences in microbiome richness (ACE, p = 0.034 and Chao1, p = 0.024), alpha diversity (Shannon, p = 0.039), and beta diversity (Bray-Curtis, p = 0.018 and Generalized UniFrac, p = 0.034) between the Aβ-NC and Aβ+MCI groups. The global SUVR was positively correlated with the genus Intestinibacter (q = 0.006) and negatively correlated with the genera Roseburia (q = 0.008) and Agathobaculum (q = 0.029). (4) Conclusions: In this study, we identified significant changes in the gut microbiota composition that occur in individuals with MCI due to AD. In particular, the correlation analysis results between PET amyloid burden and gut microbial abundance showed that amyloid deposition is associated with a reduction in specific taxa involved in butyrate production.

Redox mediator chlorophyll accelerates low-temperature biological denitrification with responses of extracellular polymers and changes in microbial community composition

Low temperatures limit the denitrification wastewater in activated sludge systems, but this can be mitigated by addition of redox mediators (RMs). Here, the effects of chlorophyll (Chl), 1,2-naphthoquinone-4-sulfonic acid (NQS), humic acid (HA), and riboflavin (RF), each tested at three concentrations, were compared for denitrification performance at low temperature, by monitoring the produced extracellular polymeric substances (EPS), and characterizing microbial communities and their metabolic potential. Chl increased the denitrification rate most, namely 4.12-fold compared to the control, followed by NQS (2.62-fold increase) and HA (1.35-fold increase), but RF had an inhibitory effect. Chl promoted the secretion of tryptophan-like and tyrosine-like proteins in the EPS and aided the conversion of protein from tightly bound EPS into loosely bound EPS, which improved the material transfer efficiency. NQS, HA, and RF also altered the EPS components. The four RMs affected the microbial community structure, whereby both conditionally abundant taxa (CAT) and conditionally rare or abundant taxa (CRAT) were key taxa. Among them, CRAT members interacted most with the other taxa. Chl promoted Flavobacterium enrichment in low-temperature activated sludge systems. In addition, Chl promoted the abundance of nitrate reduction genes narGHI and napAB and of nitrite reduction genes nirKS, norBC, and nosZ. Moreover, Chl increased abundance of genes involved in acetate metabolism and in the TCA cycle, thereby improving carbon source utilization. This study increases our understanding of the enhancement of low-temperature activated sludge by RMs, and demonstrates positive effects, in particular by Chl.

Abstract 2803: Identification of microbiome and predictive immune biomarkers in patients with advanced non-small lung cancer treated with pembrolizumab with or without chemotherapy

Abstract Background: Recent studies have shown that gut microbiota modulates antitumor immunity, and affect clinical efficacy of immune checkpoint inhibitors, including anti-programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors. We aimed to explore the metagenomic profiles of previously untreated, treatment naïve, stage IV non-small cell lung cancer (NSCLC) treated with pembrolizumab, an anti-PD1 agent with or without platinum-based chemotherapy and identify distinct ecological niche between responder and non-responder groups. Methods: We performed metagenome sequencing, whole exome sequencing (WES), and RNA sequencing (RNA-seq) on 50 patients with stage IV NSCLC, including adenocarcinoma (N=31) and squamous cell carcinoma (N=22). We employed Dirichlet Multinomial Mixtures (DMM) community typing to cluster microbial community profiling data at the genus level and analyzed the changes in microbial composition and diversity between enterotype 1 (E1, N=27) and enterotype 2 (E2, N=23). Mutation landscape including genomic alterations in relation to immune response was analyzed between responders and non-responders using WES data. Differentially expressed genes (DEGs), Gene Set Enrichment Analysis (GSEA), and immune deconvolution analysis were carried out using RNA-seq data to analyze molecular profiling of two enterotypes between the responder (N=15) and non-responder (N=35) groups. Results: The two enterotypes exhibited distinct microbial abundances and alpha diversity indices. Abundances of members of Bacteroidaceae (P=0.011) and Oscillospiraceae (P&amp;lt;0.001) were higher in E2 members, and enrichment of Lactobacillaceae (P=0.006) and Bifidobacteriaceae (P=0.041) were higher in E1. Compared to E1, the number of observed bacterial species (P&amp;lt;0.001) and Shannon index (P&amp;lt;0.001) was significantly higher in E2, indicating a healthier gut environment. The proportion of responders was higher in E2 than in E1 cluster. Comparison between responders and non-responder groups within each enterotype revealed that Lactobacillaceae showed an association with the response in E2 cluster. Mutation landscape revealed TP53 mutation as the most common mutation, more frequently observed in the E2 (100%) than in the E1 (56%) cluster. Conclusion: We explored the association between the gut microbiome and clinical response to pembrolizumab with or without combination with chemotherapy and found that E2 cluster enriched with Lactobacillaceae is associated with treatment response. Further analysis with larger cohort is ongoing. Citation Format: Jii Bum (Joy) Lee, Su-Jin Choi, Gang-Taik Lee, Junwon Yang, Hyun-Seok Oh, Arim Min, Bo-Eun Kwon, Seong-san Kang, Sujeong Baek, Dong Kwon Kim, Jae Hwan Kim, Sun Min Lim, Min Hee Hong, Kyoung-Ho Pyo, Byoung Chul Cho. Identification of microbiome and predictive immune biomarkers in patients with advanced non-small lung cancer treated with pembrolizumab with or without chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2803.