Aldex (phenylephrine/pyrilamine) / Royalty - LARVOL DELTA

Incorporating Scale Uncertainty into Differential Expression Analyses Using ALDEx2. (PubMed, Curr Protoc) - "Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Using a simple scale model for differential expression analysis to avoid dual-cutoff P value/significance thresholds Basic Protocol 2: Implementing a full informed scale model to correct scale-related data asymmetry in differential expression analyses Basic Protocol 3: Visualizing ALDEx2 outputs using a compositional approach: Principal component analysis."

Journal

Protective Effects of Grapeseed Proanthocyanidins in Ulcerative Colitis: A Pilot Study Evaluating a Potential Therapeutic Strategy. (PubMed, J Clin Med) - "Statistical analyses (Wilcoxon, ALDEx2, PERMANOVA) assessed microbial diversity and taxonomic changes between pre- and post-treatment samples...Microbiota analysis revealed enrichment of Lachnospiraceae and Sutterellaceae families, suggesting beneficial modulation. Limitations include lack of metabolic assessment and a control group, and caution is needed in interpreting zonulin measurements."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • HP

Comparative Effects of Raw Milk and Milk Replacer Feeding on Gut Microbiota Diversity and Function in Cryptosporidium parvum-Infected Neonatal Dairy Calves on a Japanese Farm. (PubMed, Vet Sci) - "Predicted microbial taxa such as Faecalibacterium (ALDEx2, effect size = 2.31, p = 0.00003) and Butyricicoccus (effect size = 1.31, p = 0.0041) were enriched in PN calves in MR...Predicted metabolic pathway profiling using a computational functional profiling approach showed the distinct metabolic pathways, including amino acid, carbohydrate, lipid, and vitamin biosynthesis, were enriched in healthier calves in both groups. These results suggest certain functional features of the microbiome could be associated with anti-inflammatory activity and short-chain fatty acid production, potentially mitigating diarrheal symptoms."

Journal • Metabolic Disorders

Analysis of gut microbiota in Restless Legs Syndrome: searching for a metagenomic signature. (PubMed, Sleep) - "Although only a few previous studies have reported the presence of small intestinal bacterial overgrowth (SIBO) in RLS, to the best of our knowledge this is the first study to highlight significant differences in the gut microbiota composition of RLS compared to both CTRL and INS, identifying a specific RLS metagenomic signature."

Journal • CNS Disorders • Inflammation • Insomnia • Mood Disorders • Movement Disorders • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Multi-marker comparative analysis of 18S, ITS1, and ITS2 primers for human gut mycobiome profiling. (PubMed, Front Bioinform) - "To improve taxonomic coverage and compositional understanding, data were examined using ALDEx2 with centered log-ratio (CLR) transformation, facilitating reliable differential abundance and effect size assessment in small sample metagenomic contexts...Despite our approach being conducted with a limited cohort to establish methodological feasibility, it brings attention to multi-marker strategies, demonstrating that integrated primer datasets surpass traditional single-marker methods in both taxonomic coverage and biomarker detection sensitivity in low-biomass fecal samples. Our research provides a reliable starting point for future studies on gut mycobiome in both healthy and diseased individuals, which could lead to better diagnostics and treatments based on microbiome profiles."

Biomarker • Journal • Oncology

Persistent human-associated microbial signatures in burial soils from the 17th and 18th century New York African burial ground. (PubMed, ISME Commun) - "Comparative analyses against six control soils from nearby urban parks were conducted using QIIME2, ALDEx2, and ANCOM...These findings demonstrate that soil microbiomes reflect host-associated microbial communities long after decomposition, providing a scalable, nondestructive approach for reconstructing ancient microbial communities and host-associated health signatures. This work establishes the NYABG burial soil microbiome as a valuable model for microbial archaeology and introduces a replicable framework for integrating environmental microbiology, bioarchaeology, and historical epidemiology through the lens of postmortem microbial ecology."

Journal

RACIAL DIFFERENCES IN THE RELATIONSHIP BETWEEN HPV PROFILES, VAGINAL MICROBIOTA, AND SEVERE CERVICAL DYSPLASIA: IMPLICATIONS FOR PRECISION CERVICAL CANCER SCREENING (IPVC 2025) - "Statistical methods included correlation analyses, PERMANOVA, ALDEx2, Fisher's exact test, and random forest modeling... Our findings demonstrate critical racial differences in how HPV co-infections, HPV diversity, and VMB disturbances influence CIN3 risk. These differences suggest distinct etiological mechanisms and underscore a potential need for tailored cervical cancer screening and prevention approaches, informed by microbiome and HPV profiles."

Cervical Cancer • Gynecology • Infectious Disease • Oncology • Solid Tumor

Gut Microbiota α- and β-Diversity, but Not Dietary Patterns, Differ Between Underweight and Normal-Weight Japanese Women Aged 20-39 Years. (PubMed, Nutrients) - "Genera contributing to group differences were identified by RDA and ANOVA-Like Differential Expression tool (ALDEx2)... Underweight women demonstrated reduced gut microbiota diversity and enrichment of taxa associated with inflammatory tendencies. Dietary therapies involving not only prebiotics but also probiotics may beneficially modulate gut microbiota and contribute to the management of low body weight."

Journal

Distribution of microsporidia in preterm and full-term infant gut microbiomes and implications for host health. (PubMed, Front Pediatr) - "Microsporidia species that were significantly different between the two groups were identified using ALDEx2...However, we wish to emphasize that the findings from this study should be interpreted with caution, considering the low sample size and comparing cohorts examined at different time points of infants' age. Future studies with larger sample sizes and more mechanistic approaches could help clarify their role in childhood development and long-term health."

Journal • CNS Disorders

Altered gut microbial networks and metabolic pathways in multiple system atrophy: a comparative 16S rRNA study. (PubMed, Front Neurosci) - "We conducted univariate and multivariable analyses to assess the differential abundance of bacterial genera and predicted metabolic pathways using four statistical ANCOM, ANCOM-BC, ALDEx2, and MaAsLin 2...Additionally, we identified an increase in the ARGORNPROST-PWY pathway (L-arginine degradation, q = 0.003) and a decrease in the PWY-6478 pathway (GDP-D-glycero-α-D-manno-heptose biosynthesis, q = 0.015) in MSA patients compared with HCs. Future studies are warranted to determine whether fecal microbiome-derived signatures can serve as reliable biomarkers for MSA."

Journal • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Multiple System Atrophy • Parkinson's Disease

Explicit Scale Simulation for analysis of RNA-sequencing count data with ALDEx2. (PubMed, NAR Genom Bioinform) - "We demonstrate the utility of scale models built based on known housekeeping genes in complex metatranscriptomic datasets. Thus this work provides guidance on how to incorporate scale into transcriptomic data sets."

Journal

metaGEENOME: an integrated framework for differential abundance analysis of microbiome data in cross-sectional and longitudinal studies. (PubMed, BMC Bioinformatics) - "Our approach effectively addresses key challenges in microbiome data analysis across both cross-sectional and longitudinal designs. Integrated into the R package metaGEENOME (https://github.com/M-Mysara/metaGEENOME), our framework provides a flexible, scalable and statistically robust solution for DA analysis, offering improved FDR control and enhanced performance for biomarker discovery in microbiome studies."

Journal • Observational data

Metabarcoding Study of Fecal Bacterial and Eukaryotic Pathogens in Stray and Pet Cats in Seoul, South Korea, 2022. (PubMed, Public Health Rep) - "This study found distinct fecal microbial communities in stray versus pet cats, with a higher prevalence of potential pathogens in stray cats. These findings emphasize the need for public health planning and effective measures for controlling stray cats."

Journal

Replacing normalizations with interval assumptions enhances differential expression and differential abundance analyses. (PubMed, BMC Bioinformatics) - "Interval assumptions enhance the rigor and reproducibility of differential expression and differential abundance analyses. Our results add to a growing body of literature arguing that normalizations should be replaced with alternative methods that allow researchers to account for scale uncertainty. However, compared to recent alternatives like scale models and sensitivity analyses, interval assumptions are easier to use, are more robust to misspecification, and have stronger and more interpretable inferential guarantees."

Journal

Distinct bladder tumor microbiome profiles between responders and non-responders to intravesical Bacillus Calmette-Guérin therapy in high-risk non-muscle invasive bladder cancer (EACR 2025) - "We conducted alpha and beta diversity analyses on responders and non-responders, followed by differential analysis using ANOVA-Like Differential Expression tool (ALDEx2).Result and In the study of bladder tumor microbiome profiles in HR-NMIBC naïve to BCG therapy, significant differences were found between responders and non-responders in microbial diversity and composition... Our findings revealed significant differences in the bladder tumor microbiome composition between BCG responders and non-responders in the HR-NMIBC. While microbiota richness and evenness were significantly lower in BCG responders compared to non-responders, certain species were still more predominant in responders. These results suggest that the bladder tumor microbiome may influence treatment outcomes, underscoring its potential as a predictive biomarker for BCG therapy."

Late-breaking abstract • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Distinct bladder tumor microbiome profiles between responders and non-responders to intravesical Bacillus Calmette-Guérin therapy in high-risk non-muscle invasive bladder cancer (EACR 2025) - "We conducted alpha and beta diversity analyses on responders and non-responders, followed by differential analysis using ANOVA-Like Differential Expression tool (ALDEx2).Result and In the study of bladder tumor microbiome profiles in HR-NMIBC naïve to BCG therapy, significant differences were found between responders and non-responders in microbial diversity and composition... Our findings revealed significant differences in the bladder tumor microbiome composition between BCG responders and non-responders in the HR-NMIBC. While microbiota richness and evenness were significantly lower in BCG responders compared to non-responders, certain species were still more predominant in responders. These results suggest that the bladder tumor microbiome may influence treatment outcomes, underscoring its potential as a predictive biomarker for BCG therapy."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Impact of smoking status on microbiome diversity and taxonomic shifts in bladder cancer (EACR 2025) - "Differential abundance (DA) analysis was conducted using ANOVA-Like Differential Expression tool (ALDEx2).Result and Analysis of alpha diversity metrics, including the Chao1 and Shannon indices, revealed no statistically significant differences in species richness or evenness among current smokers, former smokers, and non-smokers (all p > 0.05)... These findings suggest that while smoking status does not significantly impact overall microbiome diversity in bladder cancer tissues, it induces specific taxonomic shifts, particularly affecting Lactobacillales and Proteobacteria. These microbiome alterations may contribute to the understanding of microbiome-mediated mechanisms underlying smoking-related bladder cancer development."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Long-Term Human Necrobiome Dynamics: Bacterial DNA Profiling of New York African Burial Ground Soil Samples (ASM Microbe 2025) - "Relative and differential abundance analyses (ALDEx2, ANCOM, LEfSe) revealed significant taxonomic shifts (p < 0.05) in NYABG soils, with increased representation of Firmicutes, Akkermansia muciniphila, and Acinetobacter lwoffii—taxa typically found in gut and skin microbiomes—distinguishing them from non-burial soil controls...It underscores the relevance of microbial legacies in understanding historical epidemiology. By integrating metagenomic approaches, this study provides a roadmap for future investigations into historical population health and microbial evolution while motivating the incorporation of human genomics to deepen insights."

Cholera • Infectious Disease

Duckweed Surfaces Are Selectively Colonized by a Subset of Environmental Bacteria (ASM Microbe 2025) - "ALDEx2 was used to analyze differential abundance of taxa between the conditions and identified four taxa as enriched in water microbiomes relative to duckweed microbiomes...The colonized microbiomes were not distinct from those of the inoculant, as measured by Bray-Curtis similarity, and no taxa were differentially abundant between the microbiomes. This inconsistency between wild and laboratory findings brings into question the common practice of using laboratory inoculation experiments to define core taxa in the duckweed microbiome and suggests that further work is required to design a laboratory microcosm for duckweed that effectively approximates the microbial conditions encountered by this plant in the wild."

Infectious Disease

Community Profiling of Patient-Matched Pediatric Oral Plaque and Odontogenic Abscess Samples Reveals Sample-Type Specific Trends (ASM Microbe 2025) - "Significantly enriched taxa between plaque and abscess communities were rigorously evaluated using a combination of three different algorithms (MaAsLin2, ANCOMBC2, and ALDEx2)...This analysis captured abscess-enriched microbial topics, including collections of Fusobacterium, Treponema, and Prevotella, which provides insights into polymicrobial dynamics with odontogenic abscesses when compared to oral plaque. These findings will help guide future clinical work identifying bacterial biomarkers for oral disease progression within the polymicrobial environment of the oral cavity."

Clinical • Late-breaking abstract • Pediatrics

Microbial community structure and functional characteristics across the mucosal surfaces of olive flounder (Paralichthys olivaceus). (PubMed, Front Microbiol) - "To elucidate the unique roles of commensal microbes in external and internal organs, we used PICRUSt2 and ALDEx2, respectively, to predict metabolic functions and identify differential abundances of microbes...Conversely, the intestine was characterized by functions such as beta-lactamase and phenicol resistance, glycosidases, LPS synthesis, and vitamin K2 production. These findings support the idea that while the microbiota of internal organs primarily supports digestive and immunological processes, the symbionts of external organs may play crucial roles in neutralizing toxic compounds from aquaculture practices, such as reduced nitrogen and sulfur compounds, and maintaining the integrity of the mucosal barrier."

Journal

FOOD PROTEIN-INDUCED ENTEROCOLITIS SYNDROME IN CHILDREN IS ASSOCIATED WITH GUT AND SALIVARY DYSBIOSIS, WITH PARTIAL RESOLUTION AT THE END OF FOLLOW-UP AFTER TOLERANCE (ESPGHAN 2025) - "16S rRNA gene sequencing (V3-V4 regions) and biostatistical analyses (ANCOM-BC, DESeq2, LEfSe, paired ALDEx2 and MaAsLIN2) were used to compare microbiota composition between groups...Understanding the underlying mechanisms of dysbiosis is crucial to prevent and or to help in management of FPIES. A prolonged follow-up could determine if dysbiosis resolution could be complete, and if this early-infancy dysbiosis has long-term consequences on health."

Clinical • Dysbiosis • Food Hypersensitivity • Gastrointestinal Disorder • Immunology

Incorporating scale uncertainty in microbiome and gene expression analysis as an extension of normalization. (PubMed, Genome Biol) - "In practice, scale models can drastically reduce false positives and false negatives rates. We introduce updates to the popular ALDEx2 software package, available on Bioconductor, facilitating scale model analysis."

Journal

DIFFERENCES IN IBD WITH AND WITHOUT ATOPIC DISEASE: DIFFERENTIAL ABUNDANCE OF SHORT-CHAIN FATTY ACID PRODUCERS IN THE INTESTINAL MUCOSAL MICROBIOME AND ASSOCIATIONS WITH VEDOLIZUMAB USE. (DDW 2025) - "ALDEx2 was used to assess differential relative abundance in those with vs without AD. This is the first study comparing the intestinal mucosal microbiota in IBD with and without AD. Several anti-inflammatory SCFA-producing microbes were differentially abundant between groups. VDZ use was associated with a history of AD and there were related microbiome differences in AD patients on VDZ, suggesting a shared mechanism by which microbiota modulate immune responses in both AD and IBD."

Allergic Rhinitis • Asthma • Atopic Dermatitis • Dermatitis • Dermatology • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Respiratory Diseases • IL10 • TNFA

MUCOSA-ASSOCIATED INTESTINAL MICROBIOTA COMPOSITION VARIES ACROSS EIMS OF IBD (DDW 2025) - "ALDEx2 was used to assess differential relative abundances in taxa between groups at the univariate level... Our study is the first to compare the intestinal mucosal microbiome in multiple EIMs, particularly while accounting for sex, a variable known to be significantly different across most primary EIMs. Both ocular and dermatologic EIMs predominantly occurred in females, and differences in the microbiome in those with vs without dermatologic EIMs were only in part accounted for by differences in sex distribution. Notably, taxa identified differed from those previously observed as associated with joint EIMs, suggesting potentially unique contributions from the gut microbiome to different primary EIMs which warrants further study."

Dermatology • Gastroenterology • Gastrointestinal Disorder • Inflammatory Bowel Disease • Ocular Inflammation • Ophthalmology • Pyoderma Gangrenosum • Scleritis • Uveitis