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Recent years have witnessed major advances and an ever-growing list of healthcare applications for microbiome-based therapeutics. However, these advances have disproportionately targeted diseases common in high-income countries (HICs). Within low- to middle-income countries (LMIC), opportunities for microbiome-based therapeutics include sexual health epidemics, maternal health, early life mortality, malnutrition, vaccine response and infectious diseases. In this review we detail the advances that have been achieved in microbiome-based therapeutics for these areas of healthcare and identify where further work is required. Current efforts to characterise microbiomes from LMICs will aid in targeting and optimisation of therapeutics and preventative strategies specifically suited to the unmet needs within these populations. Once achieved, opportunities from disease treatment and improved treatment efficacy through to disease prevention and vector control can be effectively addressed using probiotics and live biotherapeutics. Together these strategies have the potential to increase individual health, overcome logistical challenges and reduce overall medical, individual, societal and economic costs., (© 2024 The Author(s). Microbial Biotechnology published by John Wiley & Sons Ltd.)

Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases. When applied to a Crohn's disease case-control study, our approach identifies a lack of species with the ability to consume hydrogen sulfide as the main distinguishing microbiome feature of disease. We propose that our conceptual framework will help prioritize in-depth analyses, experiments and clinical targets, and that targeting the restoration of microbial cross-feeding interactions is a promising mechanism-informed strategy to reconstruct a healthy gut ecosystem., (© 2023. Springer Nature Limited.)

Interactions between the developing microbiome and maturing immune system in early life are critical for establishment of a homeostasis beneficial to both host and commensals. The lung harbors a diverse community of microbes associated with health and local or systemic disease. We discuss how early life colonization and community changes correlate with immune development and health and disease throughout infancy, childhood, and adult life. We highlight key advances in microbiology, immunology, and computational biology that allow investigation of the functional relevance of interactions between the respiratory microbiome and host immune system, which may unlock the potential for microbiome-based therapeutics.

Summary: Shotgun metagenomic sequencing provides the capacity to understand microbial community structure and function at unprecedented resolution; however, the current analytical methods are constrained by a focus on taxonomic classifications that may obfuscate functional relationships. Here, we present expam, a tree-based, taxonomy agnostic tool for the identification of biologically relevant clades from shotgun metagenomic sequencing., Availability and Implementation: expam is an open-source Python application released under the GNU General Public Licence v3.0. expam installation instructions, source code and tutorials can be found at https://github.com/seansolari/expam., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2022. Published by Oxford University Press.)

Background: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic., Aim: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development., Methods: Here we review current and emerging approaches and assess the capabilities and weaknesses of these technologies to provide safe and effective clinical interventions. Key literature was identified through Pubmed searches with the following key words, 'microbiome', 'microbiome biomarkers', 'probiotics', 'prebiotics', 'synbiotics', 'faecal microbiota transplant', 'live biotherapeutics', 'microbiome mimetics' and 'postbiotics'., Results: Improved understanding of the human microbiome and recent technological advances provide an opportunity to develop a new generation of therapies. These therapies will range from dietary interventions, prebiotic supplementations, single probiotic bacterial strains, human donor-derived faecal microbiota transplants, rationally selected combinations of bacterial strains as live biotherapeutics, and the beneficial products or effects produced by bacterial strains, termed microbiome mimetics., Conclusions: Although methods to identify and refine these therapeutics are continually advancing, the rapid emergence of these new approaches necessitates accepted technological and ethical frameworks for measurement, testing, laboratory practices and clinical translation., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) disseminate ARGs when they mobilise into new bacterial hosts. The nature of such horizontal gene transfer (HGT) events between human gut commensals and pathogens remain poorly characterised. Here, we compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species) and find 64,188 MGE-mediated ARG transfer events between the two groups using established methods. Among the 5931 MGEs, we find 15 broad host range elements predicted to have crossed different bacterial phyla while also occurring in animal and environmental microbiomes. We experimentally demonstrate that predicted broad host range MGEs can mobilise from commensals Dorea longicatena and Hungatella hathewayi to pathogen Klebsiella oxytoca, crossing phyla simultaneously. Our work establishes the MGE-mediated ARG dissemination network between human gut commensals and pathogens and highlights broad host range MGEs as targets for future ARG dissemination management., (© 2022. The Author(s).)

Background: Human-to-human transmission of symbiotic, anaerobic bacteria is a fundamental evolutionary adaptation essential for membership of the human gut microbiota. However, despite its importance, the genomic and biological adaptations underpinning symbiont transmission remain poorly understood. The Firmicutes are a dominant phylum within the intestinal microbiota that are capable of producing resistant endospores that maintain viability within the environment and germinate within the intestine to facilitate transmission. However, the impact of host transmission on the evolutionary and adaptive processes within the intestinal microbiota remains unknown., Results: We analyze 1358 genomes of Firmicutes bacteria derived from host and environment-associated habitats. Characterization of genomes as spore-forming based on the presence of sporulation-predictive genes reveals multiple losses of sporulation in many distinct lineages. Loss of sporulation in gut Firmicutes is associated with features of host-adaptation such as genome reduction and specialized metabolic capabilities. Consistent with these data, analysis of 9966 gut metagenomes from adults around the world demonstrates that bacteria now incapable of sporulation are more abundant within individuals but less prevalent in the human population compared to spore-forming bacteria., Conclusions: Our results suggest host adaptation in gut Firmicutes is an evolutionary trade-off between transmission range and colonization abundance. We reveal host transmission as an underappreciated process that shapes the evolution, assembly, and functions of gut Firmicutes., (© 2021. The Author(s).)

The urinary tract consists of the bladder, ureters, and kidneys, and is an essential organ system for filtration and excretion of waste products and maintaining systemic homeostasis. In this capacity, the urinary tract is impacted by its interactions with other mucosal sites, including the genitourinary and gastrointestinal systems. Each of these sites harbors diverse ecosystems of microbes termed the microbiota, that regulates complex interactions with the local and systemic immune system. It remains unclear whether changes in the microbiota and associated metabolites may be a consequence or a driver of urinary tract diseases. Here, we review the current literature, investigating the impact of the microbiota on the urinary tract in homeostasis and disease including urinary stones, acute kidney injury, chronic kidney disease, and urinary tract infection. We propose new avenues for exploration of the urinary microbiome using emerging technology and discuss the potential of microbiome-based medicine for urinary tract conditions.

The prevalence of chronic immune and metabolic disorders is increasing rapidly. In particular, inflammatory bowel diseases, obesity, diabetes, asthma and chronic obstructive pulmonary disease have become major healthcare and economic burdens worldwide. Recent advances in microbiome research have led to significant discoveries of associative links between alterations in the microbiome and health, as well as these chronic supposedly noncommunicable, immune/metabolic disorders. Importantly, the interplay between diet, microbiome and the mucous barrier in these diseases has gained significant attention. Diet modulates the mucous barrier via alterations in gut microbiota, resulting in either disease onset/exacerbation due to a "poor" diet or protection against disease with a "healthy" diet. In addition, many mucosa-associated disorders possess a specific gut microbiome fingerprint associated with the composition of the mucous barrier, which is further influenced by host-microbiome and inter-microbial interactions, dietary choices, microbe immigration and antimicrobials. Our review focuses on the interactions of diet (macronutrients and micronutrients), gut microbiota and mucous barriers (gastrointestinal and respiratory tract) and their importance in the onset and/or progression of major immune/metabolic disorders. We also highlight the key mechanisms that could be targeted therapeutically to prevent and/or treat these disorders., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Metagenomic analyses have indicated that the female bladder harbors an indigenous microbiota. However, there are few cultured reference strains with sequenced genomes available for functional and experimental analyses. Here we isolate and genome-sequence 149 bacterial strains from catheterized urine of 77 women. This culture collection spans 78 species, representing approximately two thirds of the bacterial diversity within the sampled bladders, including Proteobacteria, Actinobacteria, and Firmicutes. Detailed genomic and functional comparison of the bladder microbiota to the gastrointestinal and vaginal microbiotas demonstrates similar vaginal and bladder microbiota, with functional capacities that are distinct from those observed in the gastrointestinal microbiota. Whole-genome phylogenetic analysis of bacterial strains isolated from the vagina and bladder in the same women identifies highly similar Escherichia coli, Streptococcus anginosus, Lactobacillus iners, and Lactobacillus crispatus, suggesting an interlinked female urogenital microbiota that is not only limited to pathogens but is also characteristic of health-associated commensals.

Advances in high-throughput sequencing technologies and the development of sophisticated bioinformatics analysis methods, algorithms, and pipelines to handle the large amounts of data generated have driven the field of human microbiome research forward. This specialist knowledge has been crucial to thoroughly mine the human gut microbiota, particularly in the absence of methods for the routine cultivation of most enteric microorganisms. In recent years, however, significant efforts have been made to address the 'great plate count anomaly' and to overcome the barriers to cultivation of the fastidious and mostly strictly anaerobic bacteria that reside in the human gut. As a result, many new species have been discovered, characterised, genome sequenced, and deposited in culture collections. These continually expanding resources enable experimental investigation of the human gut microbiota, validation of hypotheses made with sequence-based analyses, and phenotypic characterisation of its constituent microbes. Herein we propose a variant of Koch's postulates, aimed at providing a framework to establish causation in microbiome studies, with a particular focus on demonstrating the health-promoting role of the commensal gut microbiota., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)