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The rumen harbors a complex microbial mixture of archaea, bacteria, protozoa, and fungi that efficiently breakdown plant biomass and its complex dietary carbohydrates into soluble sugars that can be fermented and subsequently converted into metabolites and nutrients utilized by the host animal. While rumen bacterial populations have been well documented, only a fraction of the rumen eukarya are taxonomically and functionally characterized, despite the recognition that they contribute to the cellulolytic phenotype of the rumen microbiota. To investigate how anaerobic fungi actively engage in digestion of recalcitrant fiber that is resistant to degradation, we resolved genome-centric metaproteome and metatranscriptome datasets generated from switchgrass samples incubated for 48 h in nylon bags within the rumen of cannulated dairy cows. Across a gene catalog covering anaerobic rumen bacteria, fungi and viruses, a significant portion of the detected proteins originated from fungal populations. Intriguingly, the carbohydrate-active enzyme (CAZyme) profile suggested a domain-specific functional specialization, with bacterial populations primarily engaged in the degradation of hemicelluloses, whereas fungi were inferred to target recalcitrant cellulose structures via the detection of a number of endo- and exo-acting enzymes belonging to the glycoside hydrolase (GH) family 5, 6, 8, and 48. Notably, members of the GH48 family were amongst the highest abundant CAZymes and detected representatives from this family also included dockerin domains that are associated with fungal cellulosomes. A eukaryote-selected metatranscriptome further reinforced the contribution of uncultured fungi in the ruminal degradation of recalcitrant fibers. These findings elucidate the intricate networks of in situ recalcitrant fiber deconstruction, and importantly, suggest that the anaerobic rumen fungi contribute a specific set of CAZymes that complement the enzyme repertoire provided by the specialized plant cell wall degrading rumen bacteria.

Stem cells and organoids have emerged as pivotal biological tools for biologically relevant models. Together, these in vitro models realistically recapitulate structural and functional elements of the in vivo organ, allowing for studies of cellular, molecular, and genetic features that underpin various diseases that are difficult to observe in low-biomass tissues. Stem cells, and more recently organoids, have been applied in vivo as regenerative therapies. The emergence of the microbiome as an occupant throughout different body locales requires new approaches to understand the complex cellular interactions with the host tissue at each site. The success of regenerative medicine strategies and therapeutic development is intricately linked to this understanding and management of host–microbe dynamics. Interactions with the host microbiome and infections can both significantly impair tissue regeneration and compromise the function of stem cell–derived therapies. Therefore, a comprehensive understanding of how pathogens and the microbiome interact with stem cells and organoids is relevant for developing safe and effective regenerative medicine interventions. This review explores the evolving landscape of organoid technology, including a discussion on the importance of stem cell studies and considerations for organoid development that are important for use as models to study microbiome interactions. Additionally, this work describes the pivotal role of cell culture models in advancing host–microbe interaction studies in understudied low-biomass organs such as the stomach and reproductive tract. Through this assessment, we aim to shed light on the potential of these models to transform the approach to studying and managing infectious diseases within the context of regenerative medicine.

Aggressive Periodontitis (AP) and Feline Chronic Gingivostomatitis (FCGS) are two oral inflammatory diseases in cats with unknown etiology. Both conditions present with severe inflammation of the oral cavity and in FCGS it is found with additional deterioration of the non-keratinized mucosa. The oral microbiome is increasingly implicated in disease progression, but little is known about shifts in the microbial community during the AP and FCGS progression. To that end, we used deep metagenomic sequencing with total RNA on three longitudinal samples of the oral microbiome in a cat first diagnosed with AP that progressed to FCGS. This deep sequencing approach revealed that increased diversity at both the genus and species levels marked the shift from AP to FCGS, including increases in Porphyromonas and Treponema species, and decreased Streptobacillus species. The metatranscriptomes were then probed for expression of antimicrobial resistance genes and virulence factors. Disease-related genes that include cheY, and ompP5 were expressed in early AP and FCGS, while others like galU were only expressed in one or the other disease state. Both genus and species-level shifts were observed along the longitudinal microbiome samples with a noted increase in species diversity in the FCGS-associated microbiome. Corroborating that functional shifts accompany taxonomic changes, the AMR and virulence factor expression similarly changed between the sampling points. Together, these taxonomic and functional shifts indicate that AP and FCGS are potentially linked and may be marked by changes in the oral microbiome, which supports the development of microbial-based clinical diagnostics and therapeutics.

Staphylococcus aureus is a versatile zoonotic pathogen capable of causing a wide range of infections. Due to the organism’s ability to persist, recalcitrant and recurring infections are a major concern for public and animal health. This study investigated the establishment of persistence using two S. aureus strains—ATCC 29740, a bovine mastitis isolate, and USA300, a human clinical isolate—under substrate depletion. This nutritional stress established a persistence phenotype where the strains remained persistent for >120 days at notable concentrations [>2 log10 CFU/mL] and developed persister-like growth, including small colony variant formations. With RT-qPCR, we found the cell density was higher than represented by the plate count while the intracellular ATP remained constant during the persistence phase. These findings indicate that S. aureus has complex survival strategies to support its persistent state, providing a host-specific perspective when addressing recurrent infections in human and animal infectious diseases.

The rumen contains a complex mixture of microbes, crucial for the animal’s ability to degrade feed. Some of the feed-derived carbon is released as methane, a potent greenhouse gas, into the atmosphere. There is growing interest in reducing the loss of feed-derived carbon, making it available to the animal and improving animal productivity. Artificial rumen systems (ARSs) have been widely used to evaluate novel feed additives in terms of their ability to reduce methane production in the rumen and their effect on the rumen microbiome function prior to conducting resource-intensive animal trials. While the value of ARSs is widely acknowledged, it remains unclear which of these in vitro systems simulate the natural system most accurately. Here, we evaluated three different ARSs and compared them to in vivo rumen metrics. The results showed that all systems were capable of maintaining stable pH, redox potential, and temperature over time. The batch-style ARS simulated the rumen over 48 h. The semi-continuous ARS mimicked the volatile fatty acid profile and microbiota of the in vivo rumen for up to 120 h. Similarly, all ARSs maintained the prokaryotic and eukaryotic rumen populations over the duration of the study, with the semi-continuous ARS maintaining the natural rumen microbiome more accurately and for up to 120 h. In sum, our results suggest that three of the widely used ARSs simulate the rumen ecosystem adequately for many short-term rumen microbiome studies, with the more advanced semi-continuous ARS being more accurate when rumen simulation is extended to over 48 h.

Introduction: Fusobacterium nucleatum, a common oral microbe associated with periodontal disease, has emerged as a significant prognostic indicator in colorectal cancer (CRC). This organism is notably enriched in CRC tissues and is associated with reduced survival times and relapse. Fusobacterium is implicated in encouraging the development of chemoresistance through diverse tumor-promoting pathways that are increasingly being elucidated across molecular domains. Methods: This work uses a combined analysis of public data examining the role of F. nucleatum in CRC by investigating multiple transcriptomic datasets derived from co-culture infections in vitro. Results: In tandem with previously identified mechanisms known to be influenced by F. nucleatum, this analysis revealed that the bacterium activates multiple chemoresistance-associated pathways, including those driving inflammation, immune evasion, DNA damage, and metastasis. Notably, this study uncovered a novel induction of type I and type II interferon signaling, suggesting activation of a pseudo-antiviral state. Furthermore, pathway analysis (IPA) predicted altered regulation of several therapeutic agents, suggesting that F. nucleatum may compromise drug efficacy through transcriptional reprogramming. Conclusions: These findings reinforce the role of F. nucleatum in modulating host cellular pathways and support the hypothesis that bacterial association potentiates chemoresistance.

The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function. Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis ( B. infantis ) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life ( n = 34), and the second group did not administer any probiotic ( n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis -fed infants had significantly higher populations of fecal Bifidobacteriaceae , in particular B. infantis , while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes . IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.

The rumen harbors a complex microbial mixture of archaea, bacteria, protozoa, and fungi that efficiently breakdown plant biomass and its complex dietary carbohydrates into soluble sugars that can be fermented and subsequently converted into metabolites and nutrients utilized by the host animal. While rumen bacterial populations have been well documented, only a fraction of the rumen eukarya are taxonomically and functionally characterized, despite the recognition that they contribute to the cellulolytic phenotype of the rumen microbiota. To investigate how anaerobic fungi actively engage in digestion of recalcitrant fiber that is resistant to degradation, we resolved genome-centric metaproteome and metatranscriptome datasets generated from switchgrass samples incubated for 48 h in nylon bags within the rumen of cannulated dairy cows. Across a gene catalog covering anaerobic rumen bacteria, fungi and viruses, a significant portion of the detected proteins originated from fungal populations. Intriguingly, the carbohydrate-active enzyme (CAZyme) profile suggested a domain-specific functional specialization, with bacterial populations primarily engaged in the degradation of hemicelluloses, whereas fungi were inferred to target recalcitrant cellulose structures via the detection of a number of endo- and exo-acting enzymes belonging to the glycoside hydrolase (GH) family 5, 6, 8, and 48. Notably, members of the GH48 family were amongst the highest abundant CAZymes and detected representatives from this family also included dockerin domains that are associated with fungal cellulosomes. A eukaryote-selected metatranscriptome further reinforced the contribution of uncultured fungi in the ruminal degradation of recalcitrant fibers. These findings elucidate the intricate networks of in situ recalcitrant fiber deconstruction, and importantly, suggest that the anaerobic rumen fungi contribute a specific set of CAZymes that complement the enzyme repertoire provided by the specialized plant cell wall degrading rumen bacteria.

ABSTRACT Attempts to alter intestinal dysbiosis via administration of probiotics have consistently shown that colonization with the administered microbes is transient. This study sought to determine whether provision of an initial course of Bifidobacterium longum subsp. infantis (B. infantis) would lead to persistent colonization of the probiotic organism in breastfed infants. Mothers intending to breastfeed were recruited and provided with lactation support. One group of mothers fed B. infantis EVC001 to their infants from day 7 to day 28 of life (n = 34), and the second group did not administer any probiotic (n = 32). Fecal samples were collected during the first 60 postnatal days in both groups. Fecal samples were assessed by 16S rRNA gene sequencing, quantitative PCR, mass spectrometry, and endotoxin measurement. B. infantis-fed infants had significantly higher populations of fecal Bifidobacteriaceae, in particular B. infantis, while EVC001 was fed, and this difference persisted more than 30 days after EVC001 supplementation ceased. Fecal milk oligosaccharides were significantly lower in B. infantis EVC001-fed infants, demonstrating higher consumption of human milk oligosaccharides by B. infantis EVC001. Concentrations of acetate and lactate were significantly higher and fecal pH was significantly lower in infants fed EVC001, demonstrating alterations in intestinal fermentation. Infants colonized by Bifidobacteriaceae at high levels had 4-fold-lower fecal endotoxin levels, consistent with observed lower levels of Gram-negative Proteobacteria and Bacteroidetes. IMPORTANCE The gut microbiome in early life plays an important role for long-term health and is shaped in large part by diet. Probiotics may contribute to improvements in health, but they have not been shown to alter the community composition of the gut microbiome. Here, we found that breastfed infants could be stably colonized at high levels by provision of B. infantis EVC001, with significant changes to the overall microbiome composition persisting more than a month later, whether the infants were born vaginally or by caesarean section. This observation is consistent with previous studies demonstrating the capacity of this subspecies to utilize human milk glycans as a nutrient and underscores the importance of pairing a probiotic organism with a specific substrate. Colonization by B. infantis EVC001 resulted in significant changes to fecal microbiome composition and was associated with improvements in fecal biochemistry. The combination of human milk and an infant-associated Bifidobacterium sp. shows, for the first time, that durable changes to the human gut microbiome are possible and are associated with improved gut function.

Context: Co-creation—collaborative knowledge generation by academics working alongside other stakeholders—reflects a \"Mode 2\" relationship (knowledge production rather than knowledge translation) between universities and society. Co-creation is widely believed to increase research impact. Methods: We undertook a narrative review of different models of co-creation relevant to community-based health services. We contrasted their diverse disciplinary roots and highlighted their common philosophical assumptions, principles of success, and explanations for failures. We applied these to an empirical case study of a community-based research-service partnership led by the Centre of Research Excellence in Quality and Safety in Integrated Primary-Secondary Care at the University of Queensland, Australia. Findings: Co-creation emerged independently in several fields, including business studies (\"value co-creation\"), design science (\"experience-based co-design\"), computer science (\"technology co-design\"), and community development (\"participatory research\"). These diverse models share some common features, which were also evident in the case study. Key success principles included (1) a systems perspective (assuming emergence, local adaptation, and nonlinearity); (2) the framing of research as a creative enterprise with human experience at its core; and (3) an emphasis on process (the framing of the program, the nature of relationships, and governance and facilitation arrangements, especially the style of leadership and how conflict is managed). In both the literature review and the case study, co-creation \"failures\" could often be tracked back to abandoning (or never adopting) these principles. All co-creation models made strong claims for significant and sustainable societal impacts as a result of the adaptive and developmental research process; these were illustrated in the case study. Conclusions: Co-creation models have high potential for societal impact but depend critically on key success principles. To capture the nonlinear chains of causation in the co-creation pathway, impact metrics must reflect the dynamic nature and complex interdependencies of health research systems and address processes as well as outcomes.