Inflammatory bowel diseases (IBD) develop via convergence of environmental, microbial, immunological, and genetic factors. Alterations in the gut microbiota have been associated with development and ...progression of IBD, but it is not clear which populations of microbes are involved or how they might contribute to IBD. We review the genetic and environmental factors affecting the gut microbiota, the roles of gut microbes and their bioproducts in the development and clinical course of IBD, and strategies by which microbiome-based therapies can be used to prevent, manage, and eventually cure IBD. We discuss research findings that help bridge the gap between the basic sciences and clinical application.
The role of gut microbes in health and disease has often been surmised from stool, which is easily sampled and rich in microbial diversity, density, and abundance. Microbial analyses of stool have ...been accepted as measures to determine the relationship of gut microbiomes with host health and disease, based on the belief that it represents all microbial populations throughout the gut. However, functional heterogeneity of each gastrointestinal tract (GIT) segment gives rise to regional differences in gut microbial populations. Herein, we summarize the literature regarding the microbial landscape along the rostral to caudal, i.e., horizontal mouth to anus, axis of the GIT. We aim to identify gaps in the literature, particularly regarding small intestinal microbiota abundance and diversity, highlight the importance of regional microbiota on host health and disease, as well as discuss opportunities to advance this line of research.
Microbes inhabit the length of the gastrointestinal tract but differ in type and abundance in a regional fashion (mouth to colon). In this review, Martinez-Guryn, Leone, et al. examine host and environmental pressures that drive regional heterogeneity and how the regional gut microbiota influences physiological host processes and disease development.
Mounting evidence indicates that the gut microbiome responds to diet, antibiotics, and other external stimuli with speed and high precision and in ways that impact a variety of metabolic conditions ...including obesity and non-alcoholic fatty liver disease. Despite a decade of research establishing a strong association between the gut microbiota and obesity in humans, a causal relationship and the underlying mechanism remain outstanding. Several technological and methodological limitations in obesity and microbiome research have made it difficult to establish causality in this complex relationship. Additionally, limited collaborative interaction between microbiome and obesity researchers has delayed progress. Here, we discuss the current status of microbiome research as it relates to understanding obesity from the perspective of both communities, outline the underlying research challenges, and suggest directions to advance the obesity-microbiome field as a whole, with particular emphasis on the development of microbiome-targeted therapies for obesity prevention and treatment.
In this Perspective, Maruvada et al. discuss the current status of obesity-microbiome research as it relates to understanding this complex metabolic disorder, outline underlying research challenges, and suggest future directions to advance the fields, with emphasis on development of microbiome-targeted therapies for obesity prevention and treatment.
Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. ...Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension. Here, we investigate the molecular diversity of vagal sensory neurons and their roles in sensing gastrointestinal inputs. Genetic approaches allowed targeted investigation of gut-to-brain afferents involved in homeostatic responses to ingested nutrients (GPR65 neurons) and mechanical distension of the stomach and intestine (GLP1R neurons). Optogenetics, in vivo ganglion imaging, and genetically guided anatomical mapping provide direct links between neuron identity, peripheral anatomy, central anatomy, conduction velocity, response properties in vitro and in vivo, and physiological function. These studies clarify the roles of vagal afferents in mediating particular gut hormone responses. Moreover, genetic control over gut-to-brain neurons provides a molecular framework for understanding neural control of gastrointestinal physiology.
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•Genetic deconstruction of vagal afferent types that monitor and control digestion•GPR65 neurons target intestinal villi, detect nutrients, and control gut motility•GLP1R neurons form specialized terminals that detect stomach and intestine stretch•Coding of autonomic inputs in vagal ganglion and brainstem
Two types of neurons sending signals from the gut to the brain control digestion. One densely innervates intestinal villi and detects food, while another targets stomach and intestinal muscle and senses stretch.
Despite abundant evidence of malleability in speech production, previous studies of the effects of late second-language learning on first-language speech production have been limited to advanced ...learners. This study examined these effects in novice learners, adult native English speakers enrolled in elementary Korean classes. In two acoustic studies, learners' production of English was found to be influenced by even brief experience with Korean. The effect was consistently one of assimilation to phonetic properties of Korean; moreover, it occurred at segmental, subsegmental, and global levels, often simultaneously. Taken together, the results suggest that cross-language linkages are established from the onset of second-language learning at multiple levels of phonological structure, allowing for pervasive influence of second-language experience on first-language representations. The findings are discussed with respect to current notions of cross-linguistic similarity, language development, and historical sound change.
► Native English speakers produced modified English after brief Korean instruction. ► Changes in English production converged with phonetic properties of Korean. ► Korean-to-English influence showed both generality and specificity. ► Findings indicate early establishment of cross-language linkage at multiple levels.
Certain members of the gut microbiota exhibit diurnal variations in relative abundance and function to serve as non-canonical drivers of host circadian rhythms and metabolism. Also known as microbial ...oscillators, these microorganisms entrain upon non-photic cues, primarily dietary, to modulate host metabolism by providing input to both circadian clock-dependent and clock-independent host networks. Microbial oscillators are generally promoted by plant-based, low-fat (lean) diets, and most are abolished by low-fibre, high-sugar, high-fat (Western) diets. The changes in microbial oscillators under different diets then affect host metabolism by altering central and peripheral host circadian clock functions and/or by directly affecting other metabolic targets. Here, we review the unique role of the gut microbiota as a non-photic regulator of host circadian rhythms and metabolism. We describe genetic, environmental, dietary and other host factors such as sex and gut immunity that determine the composition and behaviour of microbial oscillators. The mechanisms by which these oscillators regulate host circadian gene expression and metabolic state are further discussed. Because of the gut microbiota's unique role as a non-photic driver of host metabolism and circadian rhythms, the development and clinical application of novel gut microbiota-related diagnostics and therapeutics hold great promise for achieving and maintaining metabolic health.
Inflammatory bowel diseases (IBD) are chronic, progressive diseases characterized by aberrant immune responses to environmental and gut microbial triggers in genetically susceptible hosts. Clinical, ...genetic, and experimental data support the role of gut microbes in causing and sustaining these diseases. Our understanding of IBD has changed dramatically as the result of advances in cultivation-independent approaches and computational platforms for the analysis of large data sets. However, investigations relevant to clinical observations and the natural history of the diseases will be essential for the development of microbial, genetic, and biological metrics that may be used to individualize assessment of risk and improve clinical outcomes in IBD.
A history of self-injurious thoughts and behaviors (SITBs) is consistently cited as one of the strongest predictors of future suicidal behavior. However, stark discrepancies in the literature raise ...questions about the true magnitude of these associations. The objective of this study is to examine the magnitude and clinical utility of the associations between SITBs and subsequent suicide ideation, attempts, and death.
We searched PubMed, PsycInfo, and Google Scholar for papers published through December 2014. Inclusion required that studies include at least one longitudinal analysis predicting suicide ideation, attempts, or death using any SITB variable. We identified 2179 longitudinal studies; 172 met inclusion criteria.
The most common outcome was suicide attempt (47.80%), followed by death (40.50%) and ideation (11.60%). Median follow-up was 52 months (mean = 82.52, s.d. = 102.29). Overall prediction was weak, with weighted mean odds ratios (ORs) of 2.07 95% confidence interval (CI) 1.76-2.43 for ideation, 2.14 (95% CI 2.00-2.30) for attempts, and 1.54 (95% CI 1.39-1.71) for death. Adjusting for publication bias further reduced estimates. Diagnostic accuracy analyses indicated acceptable specificity (86-87%) and poor sensitivity (10-26%), with areas under the curve marginally above chance (0.60-0.62). Most risk factors generated OR estimates of <2.0 and no risk factor exceeded 4.5. Effects were consistent regardless of sample severity, sample age groups, or follow-up length.
Prior SITBs confer risk for later suicidal thoughts and behaviors. However, they only provide a marginal improvement in diagnostic accuracy above chance. Addressing gaps in study design, assessment, and underlying mechanisms may prove useful in improving prediction and prevention of suicidal thoughts and behaviors.
Diet-induced obesity (DIO) is a significant health concern which has been linked to structural and functional changes in the gut microbiota. Exercise (Ex) is effective in preventing obesity, but ...whether Ex alters the gut microbiota during development with high fat (HF) feeding is unknown.
Determine the effects of voluntary Ex on the gastrointestinal microbiota in LF-fed mice and in HF-DIO.
Male C57BL/6 littermates (5 weeks) were distributed equally into 4 groups: low fat (LF) sedentary (Sed) LF/Sed, LF/Ex, HF/Sed and HF/Ex. Mice were individually housed and LF/Ex and HF/Ex cages were equipped with a wheel and odometer to record Ex. Fecal samples were collected at baseline, 6 weeks and 12 weeks and used for bacterial DNA isolation. DNA was subjected both to quantitative PCR using primers specific to the 16S rRNA encoding genes for Bacteroidetes and Firmicutes and to sequencing for lower taxonomic identification using the Illumina MiSeq platform. Data were analyzed using a one or two-way ANOVA or Pearson correlation.
HF diet resulted in significantly greater body weight and adiposity as well as decreased glucose tolerance that were prevented by voluntary Ex (p<0.05). Visualization of Unifrac distance data with principal coordinates analysis indicated clustering by both diet and Ex at week 12. Sequencing demonstrated Ex-induced changes in the percentage of major bacterial phyla at 12 weeks. A correlation between total Ex distance and the ΔCt Bacteroidetes: ΔCt Firmicutes ratio from qPCR demonstrated a significant inverse correlation (r2 = 0.35, p = 0.043).
Ex induces a unique shift in the gut microbiota that is different from dietary effects. Microbiota changes may play a role in Ex prevention of HF-DIO.
The gut microbiota has been implicated in the development of a number of chronic gastrointestinal and systemic diseases. These include inflammatory bowel diseases, irritable bowel syndrome, and ...metabolic (i.e. obesity, non-alcoholic fatty liver disease, and diabetes) and neurological diseases. The advanced understanding of host-microbe interactions has largely been due to new technologies such as 16S rRNA sequencing to identify previously unknown microbial communities and, more importantly, their functional characteristics through metagenomic sequencing and other multi-omic technologies, such as metatranscriptomics, metaproteomics, and metabolomics. Given the vast array of newly acquired knowledge in the field and technological advances, it is expected that mechanisms underlying several disease states involving the interactions between microbes, their metabolites, and the host will be discovered. The identification of these mechanisms will allow for the development of more precise therapies to prevent or manage chronic disease. This review discusses the functional characterization of the microbiome, highlighting the advances in identifying bioactive microbial metabolites that have been directly linked to gastrointestinal and peripheral diseases.
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