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Microbial Ecology Jul 2023The efficacy of drugs widely varies in individuals, and the gut microbiota plays an important role in this variability. The commensal microbiota living in the human gut... (Review)
Review
The efficacy of drugs widely varies in individuals, and the gut microbiota plays an important role in this variability. The commensal microbiota living in the human gut encodes several enzymes that chemically modify systemic and orally administered drugs, and such modifications can lead to activation, inactivation, toxification, altered stability, poor bioavailability, and rapid excretion. Our knowledge of the role of the human gut microbiome in therapeutic outcomes continues to evolve. Recent studies suggest the existence of complex interactions between microbial functions and therapeutic drugs across the human body. Therapeutic drugs or xenobiotics can influence the composition of the gut microbiome and the microbial encoded functions. Both these deviations can alter the chemical transformations of the drugs and hence treatment outcomes. In this review, we provide an overview of (i) the genetic ecology of microbially encoded functions linked with xenobiotic degradation; (ii) the effect of drugs on the composition and function of the gut microbiome; and (iii) the importance of the gut microbiota in drug metabolism.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Xenobiotics
PubMed: 35869999
DOI: 10.1007/s00248-022-02081-x -
Signal Transduction and Targeted Therapy Jan 2024The lungs were long thought to be sterile until technical advances uncovered the presence of the lung microbial community. The microbiome of healthy lungs is mainly... (Review)
Review
The lungs were long thought to be sterile until technical advances uncovered the presence of the lung microbial community. The microbiome of healthy lungs is mainly derived from the upper respiratory tract (URT) microbiome but also has its own characteristic flora. The selection mechanisms in the lung, including clearance by coughing, pulmonary macrophages, the oscillation of respiratory cilia, and bacterial inhibition by alveolar surfactant, keep the microbiome transient and mobile, which is different from the microbiome in other organs. The pulmonary bacteriome has been intensively studied recently, but relatively little research has focused on the mycobiome and virome. This up-to-date review retrospectively summarizes the lung microbiome's history, composition, and function. We focus on the interaction of the lung microbiome with the oropharynx and gut microbiome and emphasize the role it plays in the innate and adaptive immune responses. More importantly, we focus on multiple respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), fibrosis, bronchiectasis, and pneumonia. The impact of the lung microbiome on coronavirus disease 2019 (COVID-19) and lung cancer has also been comprehensively studied. Furthermore, by summarizing the therapeutic potential of the lung microbiome in lung diseases and examining the shortcomings of the field, we propose an outlook of the direction of lung microbiome research.
Topics: Humans; Retrospective Studies; Lung; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Microbiota
PubMed: 38228603
DOI: 10.1038/s41392-023-01722-y -
Cell Jul 2023The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of...
The gut microbiome modulates immune and metabolic health. Human microbiome data are biased toward industrialized populations, limiting our understanding of non-industrialized microbiomes. Here, we performed ultra-deep metagenomic sequencing on 351 fecal samples from the Hadza hunter-gatherers of Tanzania and comparative populations in Nepal and California. We recovered 91,662 genomes of bacteria, archaea, bacteriophages, and eukaryotes, 44% of which are absent from existing unified datasets. We identified 124 gut-resident species vanishing in industrialized populations and highlighted distinct aspects of the Hadza gut microbiome related to in situ replication rates, signatures of selection, and strain sharing. Industrialized gut microbes were found to be enriched in genes associated with oxidative stress, possibly a result of microbiome adaptation to inflammatory processes. This unparalleled view of the Hadza gut microbiome provides a valuable resource, expands our understanding of microbes capable of colonizing the human gut, and clarifies the extensive perturbation induced by the industrialized lifestyle.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Metagenome; Eukaryota; High-Throughput Nucleotide Sequencing; Metagenomics
PubMed: 37348505
DOI: 10.1016/j.cell.2023.05.046 -
Frontiers in Cellular and Infection... 2023Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as... (Review)
Review
Dysbiosis of the gut microbiome is thought to be the developmental origins of the host's health and disease through the microbiota-gut-brain (MGB) axis: such as immune-mediated, metabolic, neurodegenerative, and neurodevelopmental diseases. Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are common neurodevelopmental disorders, and growing evidence indicates the contribution of the gut microbiome changes and imbalances to these conditions, pointing to the importance of considering the MGB axis in their treatment. This review summarizes the general knowledge of gut microbial colonization and development in early life and its role in the pathogenesis of ASD/ADHD, highlighting a promising therapeutic approach for ASD/ADHD through modulation of the gut microbiome using psychobiotics (probiotics that positively affect neurological function and can be applied for the treatment of psychiatric diseases) and fecal microbial transplantation (FMT).
Topics: Humans; Autistic Disorder; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Microbiota; Gastrointestinal Microbiome; Fecal Microbiota Transplantation
PubMed: 37554355
DOI: 10.3389/fcimb.2023.1238005 -
Brain, Behavior, and Immunity Oct 2023The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS.
METHODS
Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases.
RESULTS
METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues.
CONCLUSIONS
Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mental Disorders
PubMed: 37557965
DOI: 10.1016/j.bbi.2023.08.003 -
Gut Microbes 2024Ovarian aging occurs prior to the aging of other organ systems and acts as the pacemaker of the aging process of multiple organs. As life expectancy has increased,... (Review)
Review
Ovarian aging occurs prior to the aging of other organ systems and acts as the pacemaker of the aging process of multiple organs. As life expectancy has increased, preventing ovarian aging has become an essential goal for promoting extended reproductive function and improving bone and genitourinary conditions related to ovarian aging in women. An improved understanding of ovarian aging may ultimately provide tools for the prediction and mitigation of this process. Recent studies have suggested a connection between ovarian aging and the gut microbiota, and alterations in the composition and functional profile of the gut microbiota have profound consequences on ovarian function. The interaction between the gut microbiota and the ovaries is bidirectional. In this review, we examine current knowledge on ovary-gut microbiota crosstalk and further discuss the potential role of gut microbiota in anti-aging interventions. Microbiota-based manipulation is an appealing approach that may offer new therapeutic strategies to delay or reverse ovarian aging.
Topics: Female; Humans; Gastrointestinal Microbiome; Ovary; Aging; Microbiota
PubMed: 38170622
DOI: 10.1080/19490976.2023.2295394 -
Science Advances Oct 2023The maternal microbiome is an important regulator of gestational health, but how it affects the placenta as the interface between mother and fetus remains unexplored....
The maternal microbiome is an important regulator of gestational health, but how it affects the placenta as the interface between mother and fetus remains unexplored. Here, we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate cultured endothelial cell tube formation and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.
Topics: Pregnancy; Mice; Female; Animals; Placentation; Placenta; Microbiota; Fetus; Gastrointestinal Microbiome
PubMed: 37801498
DOI: 10.1126/sciadv.adk1887 -
Neuroscience and Biobehavioral Reviews Sep 2023A fundamental shift in neuroscience suggests bidirectional interaction of gut microbiota with the healthy and dysfunctional brain. This microbiota-gut-brain axis has... (Review)
Review
A fundamental shift in neuroscience suggests bidirectional interaction of gut microbiota with the healthy and dysfunctional brain. This microbiota-gut-brain axis has mainly been investigated in stress-related psychopathology (e.g. depression, anxiety). The hippocampus, a key structure in both the healthy brain and psychopathologies, is implicated by work in rodents that suggests gut microbiota substantially impact hippocampal-dependent learning and memory. However, understanding microbiota-hippocampus mechanisms in health and disease, and translation to humans, is hampered by the absence of a coherent evaluative approach. We review the current knowledge regarding four main gut microbiota-hippocampus routes in rodents: through the vagus nerve; via the hypothalamus-pituitary-adrenal-axis; by metabolism of neuroactive substances; and through modulation of host inflammation. Next, we suggest an approach including testing (biomarkers of) the four routes as a function of the influence of gut microbiota (composition) on hippocampal-dependent (dys)functioning. We argue that such an approach is necessary to proceed from the current state of preclinical research to beneficial application in humans to optimise microbiota-based strategies to treat and enhance hippocampal-dependent memory (dys)functions.
Topics: Humans; Brain-Gut Axis; Brain; Gastrointestinal Microbiome; Microbiota; Hippocampus
PubMed: 37380040
DOI: 10.1016/j.neubiorev.2023.105296 -
Cell Host & Microbe Jul 2023The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To...
The human gut microbiome composition is generally in a stable dynamic equilibrium, but it can deteriorate into dysbiotic states detrimental to host health. To disentangle the inherent complexity and capture the ecological spectrum of microbiome variability, we used 5,230 gut metagenomes to characterize signatures of bacteria commonly co-occurring, termed enterosignatures (ESs). We find five generalizable ESs dominated by either Bacteroides, Firmicutes, Prevotella, Bifidobacterium, or Escherichia. This model confirms key ecological characteristics known from previous enterotype concepts, while enabling the detection of gradual shifts in community structures. Temporal analysis implies that the Bacteroides-associated ES is "core" in the resilience of westernized gut microbiomes, while combinations with other ESs often complement the functional spectrum. The model reliably detects atypical gut microbiomes correlated with adverse host health conditions and/or the presence of pathobionts. ESs provide an interpretable and generic model that enables an intuitive characterization of gut microbiome composition in health and disease.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Bacteria; Metagenome; Firmicutes; Bacteroides; Feces
PubMed: 37339626
DOI: 10.1016/j.chom.2023.05.024 -
Frontiers in Immunology 2023As the prevalence of allergy and autoimmune disease in industrialized societies continues to rise, improving our understanding of the mechanistic roles behind... (Review)
Review
As the prevalence of allergy and autoimmune disease in industrialized societies continues to rise, improving our understanding of the mechanistic roles behind microbiota-immune homeostasis has become critical for informing therapeutic interventions in cases of dysbiosis. Of particular importance, are alterations to intestinal microbiota occurring within the critical neonatal window, during which the immune system is highly vulnerable to environmental exposures. This review will highlight recent literature concerning mechanisms of early-life microbiota-immune homeostasis as well as discuss the potential for therapeutics in restoring dysbiosis in early life.
Topics: Infant, Newborn; Humans; Probiotics; Dysbiosis; Microbiota; Gastrointestinal Microbiome; Homeostasis
PubMed: 37936686
DOI: 10.3389/fimmu.2023.1266876