skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


This content will become publicly available on May 14, 2026

Title: Engineered Tissue Models to Decode Host–Microbiota Interactions
Abstract A mutualistic co‐evolution exists between the host and its associated microbiota in the human body. Bacteria establish ecological niches in various tissues of the body, locally influencing their physiology and functions, but also contributing to the well‐being of the whole organism through systemic communication with other distant niches (axis). Emerging evidence indicates that when the composition of the microbiota inhabiting the niche changes toward a pathogenic state (dysbiosis) and interactions with the host become unbalanced, diseases may present. In addition, imbalances within a single niche can cause dysbiosis in distant organs. Current research efforts are focused on elucidating the mechanisms leading to dysbiosis, with the goal of restoring tissue homeostasis. In vitro models can provide critical experimental platforms to address this need, by reproducing the niche cyto‐architecture and physiology with high fidelity. This review surveys current in in vitro host–microbiota research strategies and provides a roadmap that can guide the field in further developing physiologically relevant in vitro models of ecological niches, thus enabling investigation of the role of the microbiota in human health and diseases. Lastly, given the Food and Drug Administration Modernization Act 2.0, this review highlights emerging in vitro strategies to support the development and validation of new therapies on the market.  more » « less
Award ID(s):
2337322
PAR ID:
10591117
Author(s) / Creator(s):
; ; ; ; ;
Publisher / Repository:
Wiley
Date Published:
Journal Name:
Advanced Science
ISSN:
2198-3844
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. The gut microbiome incorporates the ecological niche specific to the totality of the microorganisms in the human gut. Unique to every individual, the blueprint of the microbiome sets up at birth and functions as a human organ and plays a significant role in digestion, detoxification, fighting pathogens, modulating the immune system, and improving health. The gut microbiota and associated health implications are influenced by factors such as birth and age, diseases, use of antibiotics and food components (e.g., complex carbohydrates and dietary fibers, plant proteins, unsaturated fatty acids, and functional compounds of natural origin such as flavones, flavonoids, polyphenols, and antioxidants). Toward this end, diet and the gut microbiome interact and govern each other’s fate. Herein, gut dysbiosis, the alteration of natural state and composition of the gut microbiome, and the gut microflora diversity modulated by food constituents and associated health effects have been discussed. The gut microbiota composition and related metabolites are influenced by the diet which in turn modulates human health. The outcome is deemed to aid in developing personalized diet recommendations (based on the unique gut microbiome) toward improving human health. Keywords: gut microbiome, gut microbiota, gut dysbiosis, short-chain fatty acids, metabolites, health modulation 
    more » « less
  2. ABSTRACT Host-associated microbial communities, henceforth ‘microbiota’, can affect the physiology and behavior of their hosts. In mammals, host ecological, social and environmental variables are associated with variation in microbial communities. Within individuals in a given mammalian species, the microbiota also partitions by body site. Here, we build on this work and sequence the bacterial 16S rRNA gene to profile the microbiota at six distinct body sites (ear, nasal and oral cavities, prepuce, rectum and anal scent gland) in a population of wild spotted hyenas (Crocuta crocuta), which are highly social, large African carnivores. We inquired whether microbiota at these body sites vary with host sex or social rank among juvenile hyenas, and whether they differ between juvenile females and adult females. We found that the scent gland microbiota differed between juvenile males and juvenile females, whereas the prepuce and rectal microbiota differed between adult females and juvenile females. Social rank, however, was not a significant predictor of microbiota profiles. Additionally, the microbiota varied considerably among the six sampled body sites and exhibited strong specificity among individual hyenas. Thus, our findings suggest that site-specific niche selection is a primary driver of microbiota structure in mammals, but endogenous host factors may also be influential. 
    more » « less
  3. Abstract BackgroundHybridization between evolutionary lineages has profound impacts on the fitness and ecology of hybrid progeny. In extreme cases, the effects of hybridization can transcend ecological timescales by introducing trait novelty upon which evolution can act. Indeed, hybridization can even have macroevolutionary consequences, for example, as a driver of adaptive radiations and evolutionary innovations. Accordingly, hybridization is now recognized as a motor for macrobial evolution. By contrast, there has been substantially less progress made towards understanding the positive eco-evolutionary consequences of hybridization on holobionts. Rather, the emerging paradigm in holobiont literature is that hybridization disrupts symbiosis between a host lineage and its microbiome, leaving hybrids at a fitness deficit. These conclusions, however, have been drawn based on results from predominantly low-fitness hybrid organisms. Studying “dead-end” hybrids all but guarantees finding that hybridization is detrimental. This is the pitfall that Dobzhansky fell into over 80 years ago when he used hybrid sterility and inviability to conclude that hybridization hinders evolution. Goldschmidt, however, argued that rare saltational successes—so-called hopeful monsters—disproportionately drive positive evolutionary outcomes. Goldschmidt’s view is now becoming a widely accepted explanation for the prevalence of historical hybridization in extant macrobial lineages. Aligning holobiont research with this broader evolutionary perspective requires recognizing the importance of similar patterns in host–microbiome systems. That is, rare and successful “hopeful holobionts” (i.e., hopeful monsters at the holobiont scale) might be disproportionately responsible for holobiont evolution. If true, then it is these successful systems that we should be studying to assess impacts of hybridization on the macroevolutionary trajectories of host–microbiome symbioses. ResultsIn this paper, we explore the effects of hybridization on the gut (cloacal) and skin microbiota in an ecologically successful hybrid lizard,Aspidoscelis neomexicanus. Specifically, we test the hypothesis that hybrid lizards have host-associated (HA) microbiota traits strongly differentiated from their progenitor species. Across numerous hybrid microbiota phenotypes, we find widespread evidence of transgressive segregation. Further, microbiota restructuring broadly correlates with niche restructuring during hybridization. This suggests a relationship between HA microbiota traits and ecological success. ConclusionTransgressive segregation of HA microbiota traits is not only limited to hybrids at a fitness deficit but also occurs in ecologically successful hybrids. This suggests that hybridization may be a mechanism for generating novel and potentially beneficial holobiont phenotypes. Supporting such a conclusion, the correlations that we find between hybrid microbiota and the hybrid niche indicate that hybridization might change host microbiota in ways that promote a shift or an expansion in host niche space. If true, hybrid microbiota restructuring may underly ecological release from progenitors. This, in turn, could drive evolutionary diversification. Using our system as an example, we elaborate on the evolutionary implications of host hybridization within the context of holobiont theory and then outline the next steps for understanding the role of hybridization in holobiont research. 
    more » « less
  4. Neglected tropical diseases (NTDs), particularly those caused by trypanosomatid protozoa, impose a significant global burden, disproportionately affecting underserved communities in tropical and subtropical regions. Despite their high mortality rates, associated chronic conditions, and rapid spread due to globalization and climate change, NTDs have historically received minimal research investment. Additionally, existing treatments cause severe adverse effects. While animal models have contributed significantly to our understanding of these diseases, they are limited by technical and financial constraints. Current in vitro approaches predominantly focus on single-cell interactions on stiff substrates; thus, failing to capture tissue-level dynamics crucial for understanding host-parasite interactions. In this scoping literature review, we summarize emerging engineering applications to address these challenges by developing more complex in vitro models. We discuss 36 publications that describe novel strategies employing biomaterials, organoids, spheroids, and microfluidic devices to improve the mechanistic understanding of these NTDs. We also describe how these preclinical models are being used as screening platforms in the drug discovery and repurposing pipeline. To better understand the global scope of this research, we also performed a meta-analysis of the geolocation of the authors whose work was included in this review. This analysis uncovers uneven global participation in these efforts to combat NTDs. Ultimately, we draw attention to the need for a multidisciplinary and transnational approach to mitigate the impact of trypanosomatid NTDs and reduce health inequities globally. 
    more » « less
  5. Abstract Emerging infectious diseases are increasingly recognized as a significant threat to global biodiversity conservation. Elucidating the relationship between pathogens and the host microbiome could lead to novel approaches for mitigating disease impacts. Pathogens can alter the host microbiome by inducing dysbiosis, an ecological state characterized by a reduction in bacterial alpha diversity, an increase in pathobionts, or a shift in beta diversity. We used the snake fungal disease (SFD; ophidiomycosis), system to examine how an emerging pathogen may induce dysbiosis across two experimental scales. We used quantitative polymerase chain reaction, bacterial amplicon sequencing, and a deep learning neural network to characterize the skin microbiome of free‐ranging snakes across a broad phylogenetic and spatial extent. Habitat suitability models were used to find variables associated with fungal presence on the landscape. We also conducted a laboratory study of northern watersnakes to examine temporal changes in the skin microbiome following inoculation withOphidiomyces ophidiicola. Patterns characteristic of dysbiosis were found at both scales, as were nonlinear changes in alpha and alterations in beta diversity, although structural‐level and dispersion changes differed between field and laboratory contexts. The neural network was far more accurate (99.8% positive predictive value [PPV]) in predicting disease state than other analytic techniques (36.4% PPV). The genusPseudomonaswas characteristic of disease‐negative microbiomes, whereas, positive snakes were characterized by the pathobiontsChryseobacterium,Paracoccus, andSphingobacterium. Geographic regions suitable forO. ophidiicolahad high pathogen loads (>0.66 maximum sensitivity + specificity). We found that pathogen‐induced dysbiosis of the microbiome followed predictable trends, that disease state could be classified with neural network analyses, and that habitat suitability models predicted habitat for the SFD pathogen. 
    more » « less