Microbiome in Health and Disease
Series edited by Eugene B. Chang
Host-microbe interactions are increasingly recognized for their roles in promoting health as well as in disease pathogenesis. This in-progress series was designed by current JCI Associate Editor Eugene B. Chang to highlight recent advances and challenges in understanding the human microbiome across different organ systems as well as the outlook for microbiome-targeted therapeutics.
Articles in series
Abstract
Authors
Orlando DeLeon, Eugene B. Chang
Abstract
The maternal microbiome is emerging as an important factor that influences the neurological health of mothers and their children. Recent studies highlight how microbial communities in the maternal gut can shape early-life development in ways that inform long-term health trajectories. Research on the neurodevelopmental effects of maternal microbiomes is expanding our understanding of the microbiome-gut-brain axis to include signaling across the maternal-offspring unit during the perinatal period. In this Review, we synthesize existing literature on how the maternal microbiome modulates brain function and behavior in both mothers and their developing offspring. We present evidence from human and animal studies showing that the maternal microbiome interacts with environmental factors to impact risk for neurodevelopmental abnormalities. We further discuss molecular and cellular mechanisms that facilitate maternal-offspring crosstalk for neuromodulation. Finally, we consider how advancing understanding of these complex interactions could lead to microbiome-based interventions for promoting maternal and offspring health.
Authors
Stephanie B. Orchanian, Elaine Y. Hsiao
Abstract
Human skin acts as a physical barrier to prevent the entry of pathogenic microbes while simultaneously providing a home for commensal bacteria and fungi. Microbiome sequencing studies have demonstrated the unappreciated diversity and selectivity of these microbes. Functional studies have demonstrated the impact of specific strains to tune the immune system, sculpt the microbial community, provide colonization resistance, and promote epidermal barrier integrity. Recent studies have integrated the microbiome, immunity, and tissue integrity to understand their interplay in common disorders such as atopic dermatitis. In this Review, we explore microbiome shifts associated with cutaneous disorders with an eye toward how the microbiome can be mined to identify new therapeutic opportunities.
Authors
Tiffany C. Scharschmidt, Julia A. Segre
Abstract
Asthma is a common chronic respiratory disease affecting people of all ages globally. The airway hosts diverse microbial communities increasingly recognized as influential in the development and disease course of asthma. Here, we review recent findings on the airway microbiome in asthma. As relationships between the airway microbiome and respiratory health take root early in life, we first provide an overview of the early-life airway microbiome and asthma development, where multiple cohort studies have identified bacterial genera in the infant airway associated with risk of future wheeze and asthma. We then address current understandings of interactions between environmental factors, the airway microbiome, and asthma, including the effects of rural/urban environments, pet ownership, smoking, viral illness, and antibiotics. Next, we delve into what has been observed about the airway microbiome and asthma phenotypes and endotypes, as airway microbiota have been associated with asthma control, severity, obesity-related asthma, and treatment effects as well as with type 2 high, type 2 low, and more newly described multi-omic asthma endotypes. We then discuss emerging approaches to shape the microbiome for asthma therapy and conclude the Review with perspectives on future research directions.
Authors
Young Jin Kim, Supinda Bunyavanich
Abstract
The gut microbiome has been linked to everything from human behavior to athletic performance to disease pathogenesis. And yet, few universal truths have emerged regarding how the microbiome exerts its effects or responds to the host environment except for one: gut microbiota are exquisitely sensitive to human diets. What we eat from birth onward shapes our gut microbiome composition and function, and this is likely an evolutionarily conserved interaction that benefits the microbe and often the host. However, modern diets and lifestyles have created discordance between our slowly evolving human genome and rapidly adaptable microbiome, and have been implicated in the rise of chronic diseases over the past 75 years. Diet and microbiome interactions have been reviewed extensively, so here we focus on areas of microbiome research that have most illuminated natural and disruptive dietary forces over time in humans, and where we may have opportunities to restore the natural balance of host with microbes in our modern world.
Authors
Carolina Koletic, Amanda Mrad, Anthony Martin, Suzanne Devkota
Abstract
Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don’t respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.
Authors
Francesca S. Gazzaniga, Dennis L. Kasper
Abstract
Bacterial vaginosis (BV) is a polymicrobial condition of the vaginal microbiota associated with a variety of sexually transmitted infections, infections of maternal and fetal tissues during pregnancy, and even some infections outside of the reproductive tract, including the urinary tract and mouth. BV has also been associated with conditions in which the body generates prominent inflammatory reactions to microbes, including infections of the cervix and other upper genital tract tissues. For reasons still not understood, BV is a highly recurrent and often difficult-to-treat condition, complicating attempts to prevent these associated infections. An additional layer of complexity arises from the increasing awareness that the presence of BV-associated bacteria in the vagina is not always symptomatic or associated with adverse outcomes. In this concise Review, we summarize and synthesize three groups of factors grounded in the literature that may be fueling the associations between BV and infection: (a) aspects of society and culture; (b) pathogens, virulence factors, and processes of microbial antagonism and synergy; and (c) host factors, such as genetics and immunity. Our goal is to understand what contexts and combinations of microbial, host, and social factors conspire to make BV virulent in some individuals but not others. Disrupting these patterns more systematically may achieve healthier outcomes.
Authors
Nicole M. Gilbert, Luis A. Ramirez Hernandez, Daniela Berman, Sydney Morrill, Pascal Gagneux, Amanda L. Lewis
Abstract
A large body of evidence suggests that single- and multiple-strain probiotics and synbiotics could have roles in the management of specific gastrointestinal disorders. However, ongoing concerns regarding the quality and heterogeneity of the clinical data, safety in vulnerable populations, and the lack of regulation of products containing live microbes are barriers to widespread clinical use. Safety and regulatory issues must be addressed and new technologies considered. One alternative future strategy is the use of synthetic bacterial communities, defined as manually assembled consortia of two or more bacteria originally derived from the human gastrointestinal tract. Synthetic bacterial communities can model functional, ecological, and structural aspects of native communities within the gastrointestinal tract, occupying varying nutritional niches and providing the host with a stable, robust, and diverse gut microbiota that can prevent pathobiont colonization by way of colonization resistance. Alternatively, phage therapy is the use of lytic phage to treat bacterial infections. The rise of antimicrobial resistance has led to renewed interest in phage therapy, and the high specificity of phages for their hosts has spurred interest in using phage-based approaches to precisely modulate the microbiome. In this Review, we consider the present and future of microbiome-targeting therapies, with a special focus on early-life applications, such as prevention of necrotizing enterocolitis.
Authors
Lauren E. Lynch, Rachel Lahowetz, Christian Maresso, Austen Terwilliger, Jason Pizzini, Valeria Melendez Hebib, Robert A. Britton, Anthony W. Maresso, Geoffrey A. Preidis
Abstract
Inflammatory bowel diseases (IBDs) are complex immune disorders that arise at the intersection of genetic susceptibility, environmental exposures, and dysbiosis of the gut microbiota. Our understanding of the role of the microbiome in IBD has greatly expanded over the past few decades, although efforts to translate this knowledge into precision microbiome-based interventions for the prevention and management of disease have thus far met limited success. Here we survey and synthesize recent primary research in order to propose an updated conceptual framework for the role of the microbiome in IBD. We argue that accounting for gut microbiome context — elements such disease regionality, phase of disease, diet, medication use, and patient lifestyle — is essential for the development of a clear and mechanistic understanding of the microbiome’s contribution to pathogenesis or health. Armed with better mechanistic and contextual understanding, we will be better prepared to translate this knowledge into effective and precise strategies for microbiome restitution.
Authors
Megan S. Kennedy, Eugene B. Chang
Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)