Search

Background: Parkinson's disease (PD) has been consistently linked to alterations within the gut microbiome. Objective: Our goal was to identify microbial features associated with PD incidence and progression. Methods: Metagenomic sequencing was used to characterize taxonomic and functional changes to the PD microbiome and to explore their relation to bacterial metabolites and disease progression. Motor and non‐motor symptoms were tracked using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) and levodopa equivalent dose across ≤5 yearly study visits. Stool samples were collected at baseline for metagenomic sequencing (176 PD, 100 controls). Results: PD‐derived stool samples had reduced intermicrobial connectivity and seven differentially abundant species compared to controls. A suite of bacterial functions differed between PD and controls, including depletion of carbohydrate degradation pathways and enrichment of ribosomal genes. Faecalibacterium prausnitzii‐specific reads contributed significantly to more than half of all differentially abundant functional terms. A subset of disease‐associated functional terms correlated with faster progression of MDS‐UPDRS part IV and separated those with slow and fast progression with moderate accuracy within a random forest model (area under curve = 0.70). Most PD‐associated microbial trends were stronger in those with symmetric motor symptoms. Conclusion: We provide further evidence that the PD microbiome is characterized by reduced intermicrobial communication and a shift to proteolytic metabolism in lieu of short‐chain fatty acid production, and suggest that these microbial alterations may be relevant to disease progression. We also describe how our results support the existence of gut‐first versus brain‐first PD subtypes. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Enteric pathogens navigate distinct regional microenvironments within the intestine that cue important adaptive behaviors. We investigated the response of Citrobacter rodentium, a model of human pathogenic Escherichia coli infection in mice, to regional gastrointestinal pH. We found that small intestinal pH (4.4–4.8) triggered virulence gene expression and altered cell morphology, supporting initial intestinal attachment, while higher pH, representative of C. rodentium's replicative niches further along the murine intestine, supported pathogen growth. Gastric pH, a key barrier to intestinal colonization, caused significant accumulation of intra-bacterial reactive oxygen species (ROS), inhibiting growth of C. rodentium and related human pathogens. Within-host adaptation increased gastric acid survival, which may be due to a robust acid tolerance response (ATR) induced at colonic pH. However, the intestinal environment changes throughout the course of infection. We found that murine gastric pH decreases postinfection, corresponding to increased serum gastrin levels and altered host expression of acid secretion-related genes. Similar responses following Salmonella infection may indicate a protective host response to limit further pathogen ingestion. Together, we highlight interlinked bacterial and host adaptive pH responses as an important component of host–pathogen coevolution. Enteric pathogens navigate distinct regional micro-environments along the intestinal tract. This study shows that intraluminal intestinal pH is an important spatial driver of virulence and adaptive behavior during C. rodentium infection, and is manipulated by the host in response to pathogen invasion. [ABSTRACT FROM AUTHOR]

With the global prevalence of allergic disease continuing to rise at an alarming rate, the need for effective and safe therapeutics is paramount. Given the critical role of the early-life microbiota on immune development, emerging research suggests the potential use of live biotherapeutic products (LBP) for the prevention and treatment of childhood allergy. However, findings are limited and inconsistent. Therefore, the present review critically evaluates the current animal and human data on the therapeutic value of LBPs in allergy, the underlying immunological mechanisms by which LBPs may mediate allergy susceptibility, limitations of the current research that need to be addressed, and future research directions. Accordingly, LBPs may protect against allergic disease through several immunological and physiological mechanisms during early-life, including regulation of Th1/Th2 balance, SCFA-induced activation of GPR41/43 and HDAC inhibition, and maturation of epithelial barrier integrity. Taken together, current findings indicate powerful immunomodulatory properties of LBPs on allergic immune response, with LBPs offering exciting potential as a novel therapeutic tool for childhood allergy. However, the efficacy of LBPs in allergy is complex and influenced by many population and methodological factors, resulting in varied therapeutic benefits. While research thus far has focused on traditional probiotic strains, greater investigation into microbial consortiums selected from the microbiota of non-allergic infants may provide greater promise as a therapeutic tool for allergic disease. Further investigation, particularly into long-term efficacy, strain-specific effects, optimal supplementation regimes, and use of multi-strain consortiums, is necessary before findings can be translated into clinical applications to tackle childhood allergic disease. [ABSTRACT FROM AUTHOR]

There is increasing evidence that interactions between microbes and their hosts not only play a role in determining health and disease but also in emotions, thought, and behavior. Built environments greatly influence microbiome exposures because of their built-in highly specific microbiomes coproduced with myriad metaorganisms including humans, pets, plants, rodents, and insects. Seemingly static built structures host complex ecologies of microorganisms that are only starting to be mapped. These microbial ecologies of built environments are directly and interdependently affected by social, spatial, and technological norms. Advances in technology have made these organisms visible and forced the scientific community and architects to rethink gene-environment and microbe interactions respectively. Thus, built environment design must consider the microbiome, and research involving host-microbiome interaction must consider the built-environment. This paradigm shift becomes increasingly important as evidence grows that contemporary built environments are steadily reducing the microbial diversity essential for human health, well-being, and resilience while accelerating the symptoms of human chronic diseases including environmental allergies, and other more life-altering diseases. New models of design are required to balance maximizing exposure to microbial diversity while minimizing exposure to human-associated diseases. Sustained trans-disciplinary research across time (evolutionary, historical, and generational) and space (cultural and geographical) is needed to develop experimental design protocols that address multigenerational multispecies health and health equity in built environments. [ABSTRACT FROM AUTHOR]

Background: The microbiome has a pivotal role in intestinal health, and nutrition has a major role shaping its structure. Enteral deprivation, in which no oral/enteral nutrition is administered, is common in hospitalized/gastrointestinal patients. The dynamics that enteral deprivation exerts on the microbial community, specifically in the small intestine, are not well understood. Methods: Enteral deprivation was modeled with exclusive parenteral nutrition (EPN) mice. Mice were allocated to receive either EPN or saline and chow (control) and euthanized after 0, 2, 4, or 6 days. DNA was extracted from jejunum, ileum, and colon content. 16S sequencing was used to compare changes in microbial communities between groups. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Results: EPN‐treated mice showed community changes throughout the intestine. Beta diversity in colon showed clear separation between the groups (Bray‐Curtis, P < 0.001). Time‐dependent dynamics were seen in ileal but not jejunal samples. Alpha diversity was lower in the colon of EPN mice compared with control/baseline mice (Chao1, P < 0.01) but not in ileum/jejunum. Progressive loss of single‐taxon domination was seen, most notably in the small intestine. This was accompanied by increases/decreases in specific taxa. A clear separation was seen in the functional capacity of the community between fed and enterally deprived mice at the ileum and colon, which was observed early on. Conclusions: Enteral deprivation disturbs the microbial community in a spatial and dynamic manner. There should be further focus on studying the effect of these changes on the host. [ABSTRACT FROM AUTHOR]

Background. Studies suggest that early-life gut microbiota composition and intestinal short-chain fatty acids (SCFAs) are linked to future asthma susceptibility. Furthermore, infancy offers a critical time window to modulate the microbiota and associated metabolites through diet-microbe interactions to promote infant health. Human milk oligosaccharides (HMOs), nondigestible carbohydrates abundant in breast milk, are prebiotics selectively metabolized by gut microbiota that consequently modify microbiome composition and SCFA production. Methods. Using a house dust mite mouse model of allergy, we investigated the impacts of early oral treatment of pups with biologically relevant doses of 2′-fucosyllactose (2′-FL) and 6′-sialyllactose (6′-SL), two of the most abundant HMOs in human milk, in amelioration of allergic airway disease severity. Results. We found that administration of 2′-FL and 6′-SL during early life reduced lung histopathology scores, circulating IgE, cytokine levels, and inflammatory cell infiltration, all hallmark symptoms of allergic asthma. HMO supplementation also increased the relative abundance of intestinal Bacteroidetes and Clostridia, known SCFA producers within the gut. Indeed, we detected increased SCFA concentrations in both the intestine and blood of adult mice who received HMOs prior to weaning. Conclusion. We propose a model in which orally administered HMOs delivered during early life shift the microbiota toward increased production of SCFAs, which dampens the allergic immune responses behind allergy and asthma. Overall, these data suggest the potential for HMO supplementation to protect infants against asthma development later in life, with possible benefits against additional atopic diseases such as eczema and food allergies. [ABSTRACT FROM AUTHOR]

The coronavirus disease has swept the world, bringing scientists from multiple disciplines together to work on a focused cause. In this forum, we discuss different roles that microbiota, malnutrition, and immunity have on severity of coronavirus disease and the importance of studying them from a gut-systemic perspective using multi-omics approaches. [ABSTRACT FROM AUTHOR]