le petit prince
animals in a bacterial world, a new imperative for the life sciences
mcfall–ngai et al 2013
i, superorganism: learning to love your inner ecosystem
jon turney 2015 9781848318229
gut: the inside story of the body’s most under–rated organ
giulia enders 2015 978-1-77164-150-0
brain maker: the power of gut microbes to heal and protect your brain — for life
david perlmutter 2015
the psychobiotic revolution: mood, food and the new science of the gut-brain connection
microbes can help explain the evolution of host altruism
ohad lewin-epstein, ranit aharonov & lilach hadany 2017
trees, fungi and bacteria: tripartite metatranscriptomics of a root microbiome responding to soil contamination
e. gonzalez et al. 2018
microbial genetic composition tunes host longevity
bing han et al. 2017
•Systematic analysis of longevity-promoting microbial genetic variations •Colanic acid as a pro-longevity natural compound effective in different species •Bacterial metabolites regulate host mitochondrial dynamics and UPRmit
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPRmt) in the host. Purified CA polymers are sufficient to promote longevity via ATFS-1, the host UPRmt-responsive transcription factor. Furthermore, the mitochondrial changes and longevity effects induced by CA are conserved across different species. Together, our results identified molecular targets for developing pro-longevity microbes and a bacterial metabolite acting on host mitochondria to promote longevity.
"These findings are also interesting and have implications from the biological point of view in the way we understand host-microbe communication," Wang said. "Mitochondria seem to have evolved from bacteria that millions of years ago entered primitive cells. Our finding suggests that products from bacteria today can still chime in the communication between mitochondria in our cells. We think that this type of communication is very important and here we have provided the first evidence of this. Fully understanding microbe-mitochondria communication can help us understand at a deeper level the interactions between microbes and their hosts."
harbouring public good mutants within a pathogen population can increase both fitness and virulence
richard j lindsay et al 2016
numerous uncharacterized and highly divergent microbes which colonize humans are revealed by circulating cell-free dna
mark kowarsky et al. 2017
Through massive shotgun sequencing of circulating cell-free DNA from the blood of more than 1,000 independent samples, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Previous studies targeted specific niches such as feces, skin, or the oral cavity, whereas our approach of using blood effectively enables sampling of the entire body and reveals the colonization of niches which have been previously inaccessible. We were thus able to discover that the human body contains a vast and unexpected diversity of microbes, many of which have highly divergent relationships to the known tree of life.
Blood circulates throughout the human body and contains molecules drawn from virtually every tissue, including the microbes and viruses which colonize the body. Through massive shotgun sequencing of circulating cell-free DNA from the blood, we identified hundreds of new bacteria and viruses which represent previously unidentified members of the human microbiome. Analyzing cumulative sequence data from 1,351 blood samples collected from 188 patients enabled us to assemble 7,190 contiguous regions (contigs) larger than 1 kbp, of which 3,761 are novel with little or no sequence homology in any existing databases. The vast majority of these novel contigs possess coding sequences, and we have validated their existence both by finding their presence in independent experiments and by performing direct PCR amplification. When their nearest neighbors are located in the tree of life, many of the organisms represent entirely novel taxa, showing that microbial diversity within the human body is substantially broader than previously appreciated.
microbiota diurnal rhythmicity programs host transcriptome oscillations
christoph a. thaiss et al. 2016
Intestinal microbiota biogeography and metabolome undergo diurnal oscillations
Circadian oscillations of serum metabolites are regulated by the microbiota
Microbiota rhythms program the circadian epigenetic and transcriptional landscape
The microbiota regulates the circadian liver transcriptome and detoxification pattern
The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.
hierarchical social networks shape gut microbial composition in wild verreaux’s sifaka
amanda c. perofsky et al. 2017
gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes
liping zhao et al. 2018
microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases
rachel fellows et al. 2017
glucocorticoids and gut bacteria: “the galf hypothesis” in the metagenomic era
david j. morris, jason m. ridlon 2017
The gut microbiota are implicated causally in essential hypertension.
A proposed mechanism of essential hypertension is production of endogenous of glycerrhetinic acid-like factors (GALFs)
GALFs act as competitive inhibitors of renal 11β-hydroxysteroid dehydrogenase.
Gut bacteria are capable of converting host glucocorticoids into GALFs.
A new concept is emerging in biomedical sciences: the gut microbiota is a virtual ‘organ’ with endocrine function. Here, we explore the literature pertaining to the role of gut microbial metabolism of endogenous adrenocorticosteroids as a contributing factor in the etiology of essential hypertension. A body of literature demonstrates that bacterial products of glucocorticoid metabolism are absorbed into the portal circulation, and pass through the kidney before excretion into urine. Apparent mineralocorticoid excess (AME) syndrome patients were found to have congenital mutations resulting in non-functional renal 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) and severe hypertension often lethal in childhood. 11β-HSD2 acts as a “guardian” enzyme protecting the mineralocorticoid receptor from excess cortisol, preventing sodium and water retention in the normotensive state. Licorice root, whose active ingredient, glycerrhetinic acid (GA), inhibits renal 11β-HSD2, and thereby causes hypertension in some individuals. Bacterially derived glucocorticoid metabolites may cause hypertension in some patients by a similar mechanism. Parallel observations in gut microbiology coupled with screening of endogenous steroids as inhibitors of 11β-HSD2 have implicated particular gut bacteria in essential hypertension through the production of glycerrhetinic acid-like factors (GALFs). A protective role of GALFs produced by gut bacteria in the etiology of colorectal cancer is also explored.
drosophila adaptation to viral infection through defensive symbiont evolution
vitor g. faria, nelson e. martins, sara magalhães, tânia f. paulo, viola nolte, christian schlötterer, élio sucena, luis teixeira 2016
Microbial symbionts can modulate host interactions with biotic and abiotic factors. Such interactions may affect the evolutionary trajectories of both host and symbiont. Wolbachia protects Drosophila melanogaster against several viral infections and the strength of the protection varies between variants of this endosymbiont. Since Wolbachia is maternally transmitted, its fitness depends on the fitness of its host. Therefore, Wolbachia populations may be under selection when Drosophila is subjected to viral infection. Here we show that in D. melanogaster populations selected for increased survival upon infection with Drosophila C virus there is a strong selection coefficient for specific Wolbachia variants, leading to their fixation. Flies carrying these selected Wolbachia variants have higher survival and fertility upon viral infection when compared to flies with the other variants. These findings demonstrate how the interaction of a host with pathogens shapes the genetic composition of symbiont populations. Furthermore, host adaptation can result from the evolution of its symbionts, with host and symbiont functioning as a single evolutionary unit.
Animals live in close association with microbial partners that can shape many aspects of their lives. For instance, several insects carry bacteria that defend them against parasites and infectious diseases. The intracellular bacterium Wolbachia protects the fruit fly Drosophila melanogaster against viral infection. Natural populations of Drosophila carry different variants of Wolbachia, which differ from one another in the strength of this protection. Here we show that a population of Drosophila infected with viruses during several generations adapts to this challenge through turnover in Wolbachia composition. The Wolbachia variants that give higher protection to viruses, by increasing fly survival and fecundity upon infection, are strongly selected. This work demonstrates that the interaction of an animal with a pathogen can shape its associated microbial populations. We show that adaptation to pathogens can be achieved not only through selection of resistance on the host proper but also through the evolutionary shaping of its microbial community.
complex pectin metabolism by gut bacteria reveals novel catalytic functions
didier ndeh et al. 2017
akkermansia muciniphila mediates negative effects of ifnγ on glucose metabolism
renee l. greer 2016
diet-microbiota interactions mediate global epigenetic programming in multiple host tissues
kimberly a. krautkramer et al. 2016
Gut microbiota alter host histone acetylation and methylation in multiple tissues
Western diet suppresses microbiota-driven SCFA production and chromatin effects
SCFAs recapitulate microbiota-driven chromatin and transcriptional effects
Histone-modifying enzymes regulate transcription and are sensitive to availability of endogenous small-molecule metabolites, allowing chromatin to respond to changes in environment. The gut microbiota produces a myriad of metabolites that affect host physiology and susceptibility to disease; however, the underlying molecular events remain largely unknown. Here we demonstrate that microbial colonization regulates global histone acetylation and methylation in multiple host tissues in a diet-dependent manner: consumption of a “Western-type” diet prevents many of the microbiota-dependent chromatin changes that occur in a polysaccharide-rich diet. Finally, we demonstrate that supplementation of germ-free mice with short-chain fatty acids, major products of gut bacterial fermentation, is sufficient to recapitulate chromatin modification states and transcriptional responses associated with colonization. These findings have profound implications for understanding the complex functional interactions between diet, gut microbiota, and host health.
intestinal serotonin transporter inhibition by toll-like receptor 2 activation. a feedback modulation
latorre e, layunta e, grasa l, castro m, pardo j, gomollón f, et al. 2016
human age and skin physiology shape diversity and abundance of archaea on skin
christine moissl-eichinger et al. 2017
a commensal strain of staphylococcus epidermidis protects against skin neoplasia
teruaki nakatsuji et al. 2018
stochastic assembly produces heterogeneous communities in the caenorhabditis elegans intestine
nicole m. vega, jeff gore 2017
Host-associated bacterial communities vary extensively between individuals, but it can be very difficult to determine the sources of this heterogeneity. Here, we demonstrate that stochastic bacterial community assembly in the Caenorhabditis elegans intestine is sufficient to produce strong interworm heterogeneity in community composition. When worms are fed with two neutrally competing, fluorescently labeled bacterial strains, we observe stochastically driven bimodality in community composition, in which approximately half of the worms are dominated by each bacterial strain. A simple model incorporating stochastic colonization suggests that heterogeneity between worms is driven by the low rate at which bacteria successfully establish new intestinal colonies. We can increase this rate experimentally by feeding worms at high bacterial density; in these conditions, the bimodality disappears. These results demonstrate that demographic noise is a potentially important driver of diversity in bacterial community formation and suggest a role for C. elegans as a model system for ecology of host-associated communities.
Host-associated bacterial communities—also known as microbiomes—vary extensively between individuals, even among clones exposed to the same environment. The sources of this variation are not entirely understood and can be very difficult to determine. In this manuscript, we demonstrate experimentally how randomness in bacterial colonization can result in large differences in the composition of host-associated bacterial communities, using the nematode worm Caenorhabditis elegans as a tractable host model. We find that the amount of variation between individual communities is a function of two rates relevant to how bacteria colonize the host intestine: the colonization rate and the birth rate. We can manipulate the degree of variation between communities by altering the colonization rate, using the amount of bacteria presented to the worms to control the rate at which migrants enter the intestine. When worms are fed with two neutrally competing, fluorescently labeled bacterial strains at low colonization rates, we are able to produce noise-induced bistability in this system, in which each community is dominated by bacteria of only one color. These results demonstrate the potential importance of noise and randomness as a driver of variation between communities and highlight the utility of the simple model organism C. elegans for studying questions relevant to host-associated microbial communities.
system that is stable without diffusion becomes unstable in the presence of diffusion. Turing was motivated to understand morphogenesis with this example of instability
differential human gut microbiome assemblages during soil-transmitted helminth infections in indonesia and liberia
bruce a. rosa et al. 2018
gut microbiota orchestrates energy homeostasis during cold
chevalier et al 2015
exercise alters gut microbiota composition and function in lean and obese humans
jacob m. allen et al. 2017
non-classical immunity controls microbiota impact on skin immunity and tissue repair
jonathan l. linehan et al. 2018
•Non-classical MHC class I molecules promote homeostatic immunity to the microbiota
•Commensal-specific T cells express immunoregulatory and tissue repair signatures
•Commensal-specific T cells accelerate wound closure
Mammalian barrier surfaces are constitutively colonized by numerous microorganisms. We explored how the microbiota was sensed by the immune system and the defining properties of such responses. Here, we show that a skin commensal can induce T cell responses in a manner that is restricted to non-classical MHC class I molecules. These responses are uncoupled from inflammation and highly distinct from pathogen-induced cells. Commensal-specific T cells express a defined gene signature that is characterized by expression of effector genes together with immunoregulatory and tissue-repair signatures. As such, non-classical MHCI-restricted commensal-specific immune responses not only promoted protection to pathogens, but also accelerated skin wound closure. Thus, the microbiota can induce a highly physiological and pleiotropic form of adaptive immunity that couples antimicrobial function with tissue repair. Our work also reveals that non-classical MHC class I molecules, an evolutionarily ancient arm of the immune system, can promote homeostatic immunity to the microbiota.
characterization of metabolic responses to healthy diets and association with blood pressure: application to the optimal macronutrient intake trial for heart health (omniheart), a randomized controlled study
ruey leng loo et al. 2018
gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals
christian benedict, heike vogel, wenke jonas, anni woting, michael blaut, annette schürmann, jonathan cedernaes 2016
microbial regulation of microrna expression in the amygdala and prefrontal cortex
alan e. hoban et al. 2017
environment dominates over host genetics in shaping human gut microbiota
daphna rothschild et al. 2018
the gut microbiota and autism spectrum disorders
qinrui li et al. 2017
the airway microbiome at birth
charitharth vivek lal et al 2016
exposure to bacterial cpg dna protects from airway allergic inflammation by expanding regulatory lung interstitial macrophages
catherine sabatel et al. 2017
sex-specific impact of asthma during pregnancy on infant gut microbiota
petya t. koleva et al. 2017
serum cortisol mediates the relationship between fecal ruminococcus and brain n-acetylaspartate in the young pig
austin t. mudd et al. 2017
trim28 controls a gene regulatory network based on endogenous retroviruses in human neural progenitor cells
per ludvik brattås et al. 2017
•Stage- and region-specific expression of ERVs during human brain development
•TRIM28 binds to ERVs and induces hetereochromatin in human neural progenitor cells
•Knockdown of TRIM28 in hNPCs results in the upregulation of ERV expression
•Protein-coding genes located near upregulated ERVs are upregulated
Endogenous retroviruses (ERVs), which make up 8% of the human genome, have been proposed to participate in the control of gene regulatory networks. In this study, we find a region- and developmental stage-specific expression pattern of ERVs in the developing human brain, which is linked to a transcriptional network based on ERVs. We demonstrate that almost 10,000, primarily primate-specific, ERVs act as docking platforms for the co-repressor protein TRIM28 in human neural progenitor cells, which results in the establishment of local heterochromatin. Thereby, TRIM28 represses ERVs and consequently regulates the expression of neighboring genes. These results uncover a gene regulatory network based on ERVs that participates in control of gene expression of protein-coding transcripts important for brain development.
bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration
bjoern o. schroeder et al. 2017
•Western style diet impairs penetrability and growth of the colonic mucus layer in mice
Mucus defects are accompanied by distinct alterations in microbiota composition
•Microbiota transplant from chow-fed mice prevents mucus aberrations in mice fed a WSD
•Mucus aberrations can be prevented by Bifidobacterium longum and inulin treatment
Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.
mediated nourishment of gut microbiota protects against diet-induced obesity by restoring il-22-mediated colonic health
jun zou et al. 2017
•The fermentable fiber inulin prevented high-fat diet (HFD)-induced metabolic syndrome
•HFD enriched with inulin increased gut epithelial proliferation, prevented colon atrophy
•Inulin restored HFD-induced microbiota depletion and microbiota-mucosa separation
•Inulin effects are microbiota and IL-22, but not short-chain fatty acid, dependent
Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function.
intrapartum antibiotics for gbs prophylaxis alter colonization patterns in the early infant gut microbiome of low risk infants
jennifer c. stearns et al. 2017
antibiotic-associated hemorrhagic colitis (AAHC)
one mechanism for antibiotics to cause damage, through imbalance of toxin-producing part of microbiome
biosynthesis of the enterotoxic pyrrolobenzodiazepine natural product tilivalline
elisabeth dornisch et al. 2017
seasonal cycling in the gut microbiome of the hadza hunter-gatherers of tanzania
samuel a. smits et al. 2017
the gut microbiota of healthy aged chinese is similar to that of the healthy young
gaorui bian 2017
the gut microbiota of rural papua new guineans: composition, diversity patterns, and ecological processes
inés martínez et al. 2015
•The fecal microbiota in PNG is more diverse but less individualized than in the US
•Most bacterial species are shared among PNG and the US, but abundance profiles differ
•Impact of lifestyle on ecological assembly processes might explain these patterns
•Westernization may decrease bacterial dispersal rates, altering microbiota structure
Although recent research revealed an impact of westernization on diversity and composition of the human gut microbiota, the exact consequences on metacommunity characteristics are insufficiently understood, and the underlying ecological mechanisms have not been elucidated. Here, we have compared the fecal microbiota of adults from two non-industrialized regions in Papua New Guinea (PNG) with that of United States (US) residents. Papua New Guineans harbor communities with greater bacterial diversity, lower inter-individual variation, vastly different abundance profiles, and bacterial lineages undetectable in US residents. A quantification of the ecological processes that govern community assembly identified bacterial dispersal as the dominant process that shapes the microbiome in PNG but not in the US. These findings suggest that the microbiome alterations detected in industrialized societies might arise from modern lifestyle factors limiting bacterial dispersal, which has implications for human health and the development of strategies aimed to redress the impact of westernization.
heat-killed lactobacillus casei confers broad protection against influenza a virus primary infection and develops heterosubtypic immunity against future secondary infection
yu-jin jung et al. 2017
translocation of a gut pathobiont drives autoimmunity in mice and humans
s. manfredo vieira et al. 2018
prenatal exposure to a mother’s stress contributes to anxiety and cognitive problems that persist into adulthood, a phenomenon that could be explained by lasting – and potentially damaging – changes in the microbiome, according to new research in mice
age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction
netusha thevaranjan et al. 2017
•Age-associated inflammation drives macrophage dysfunction and tissue damage
•Mice under germ-free conditions are protected from age-associated inflammation
•Co-housing germ-free mice with old, but not young, mice increases age-related inflammation
•Age-related microbiota changes can be reversed by reducing TNF levels
Levels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts, and macrophages derived from aged germ-free mice maintain anti-microbial activity. Co-housing germ-free mice with old, but not young, conventionally raised mice increases pro-inflammatory cytokines in the blood. In tumor necrosis factor (TNF)-deficient mice, which are protected from age-associated inflammation, age-related microbiota changes are not observed. Furthermore, age-associated microbiota changes can be reversed by reducing TNF using anti-TNF therapy. These data suggest that aging-associated microbiota promote inflammation and that reversing these age-related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity.
recurrent infection progressively disables host protection against intestinal inflammation
won ho yang et al. 2017
identification of the ligand of pru p 3, a peach ltp
nuria cubells-baeza et al. 2017
glyphosate’s suppression of cytochrome p450 enzymes and amino acid biosynthesis by the gut microbiome: pathways to modern diseases
anthony samsel and stephanie seneff 2013
antibiotic-induced changes to the host metabolic environment inhibit drug efficacy and alter immune function
jason h. yang et al. 2017
Antibiotic treatment depletes central metabolism intermediates in the peritoneum
Antibiotic treatment elicits microbiome-independent changes in host metabolites
Metabolites altered by antibiotic treatment during infection inhibit drug efficacy
Antibiotic treatment impairs phagocytic killing by inhibiting respiratory activity
Bactericidal antibiotics alter microbial metabolism as part of their lethality and can damage mitochondria in mammalian cells. In addition, antibiotic susceptibility is sensitive to extracellular metabolites, but it remains unknown whether metabolites present at an infection site can affect either treatment efficacy or immune function. Here, we quantify local metabolic changes in the host microenvironment following antibiotic treatment for a peritoneal Escherichia coli infection. Antibiotic treatment elicits microbiome-independent changes in local metabolites, but not those distal to the infection site, by acting directly on host cells. The metabolites induced during treatment, such as AMP, reduce antibiotic efficacy and enhance phagocytic killing. Moreover, antibiotic treatment impairs immune function by inhibiting respiratory activity in immune cells. Collectively, these results highlight the immunomodulatory potential of antibiotics and reveal the local metabolic microenvironment to be an important determinant of infection resolution.
the active component of aspirin, salicylic acid, promotes staphylococcus aureus biofilm formation in a pia-dependent manner
cristian dotto et al. 2017
breast tissue, oral and urinary microbiomes in breast cancer
hannah wang et al. 2017
patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria
christine m. dejea et al. 2018
bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells
liam chung et al. 2018
•B. fragilis toxin-induced tumorigenesis requires epithelial IL17 and Stat3 signaling
•IL17 targets colonic epithelial cells (CECs) to promote ETBF-mediated carcinogenesis
•IL17-activated NF-κb signaling in CECs triggers C-X-C chemokine expression
•NF-κB-induced chemokines direct pro-tumoral myeloid infiltration to distal colon
Pro-carcinogenic bacteria have the potential to initiate and/or promote colon cancer, in part via immune mechanisms that are incompletely understood. Using ApcMin mice colonized with the human pathobiont enterotoxigenic Bacteroides fragilis (ETBF) as a model of microbe-induced colon tumorigenesis, we show that the Bacteroides fragilis toxin (BFT) triggers a pro-carcinogenic, multi-step inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling in colonic epithelial cells (CECs). Although necessary, Stat3 activation in CECs is not sufficient to trigger ETBF colon tumorigenesis. Notably, IL-17-dependent NF-κB activation in CECs induces a proximal to distal mucosal gradient of C-X-C chemokines, including CXCL1, that mediates the recruitment of CXCR2-expressing polymorphonuclear immature myeloid cells with parallel onset of ETBF-mediated distal colon tumorigenesis. Thus, BFT induces a pro-carcinogenic signaling relay from the CEC to a mucosal Th17 response that results in selective NF-κB activation in distal colon CECs, which collectively triggers myeloid-cell-dependent distal colon tumorigenesis.
gut microbiota regulate motor deficits and neuroinflammation in a model of parkinson’s disease
timothy r. sampson et al. 2016
Gut microbes promote α-synuclein-mediated motor deficits and brain pathology
Depletion of gut bacteria reduces microglia activation
SCFAs modulate microglia and enhance PD pathophysiology
Human gut microbiota from PD patients induce enhanced motor dysfunction in mice
The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson’s disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice
elise l. ma et al. 2017
the role of microbial amyloid in neurodegeneration
robert p. friedland, matthew r. chapman 2017
cutaneous leishmaniasis induces a transmissible dysbiotic skin microbiota that promotes skin inflammation
ciara gimblet et al. 2017
Leishmania infection alters the skin microbiota of both humans and mice
Dysbiosis is characterized by a dominance of Staphylococcus and/or Streptococcus
Naive mice acquire dysbiosis when co-housed with leishmania-infected mice
Acquiring a dysbiotic microbiota prior to infection exacerbates skin inflammation
Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases.
extreme dysbiosis of the microbiome in critical illness
daniel mcdonald et al 2016
reduction of abeta amyloid pathology in appps1 transgenic mice in the absence of gut microbiota
t. harach et al. 2017
differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome
jennifer s. labus et al. 2017
endothelial tlr4 and the microbiome drive cerebral cavernous malformations
alan t. tang et al. 2017
loss of paneth cell autophagy causes acute susceptibility to toxoplasma gondii-mediated inflammation
elise burger et al. 2018
•Basal Paneth cell autophagy is driven by the microbiota and IFN-γ
•Paneth cell autophagy protects against acute infection
•Loss of Paneth cell autophagy results in impaired intestinal permeability
•Loss of Paneth cell autophagy leads to TNF- and IFN-γ mediated intestinal pathology
The protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by IFN-γ- and intestinal microbiota-mediated inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a prominent secretory epithelial cell type that resides at the base of intestinal crypts and releases antimicrobial peptides. We demonstrate that the microbiota triggers basal Paneth cell-specific autophagy via induction of IFN-γ, a known trigger of autophagy, to maintain intestinal homeostasis. Deletion of the autophagy protein Atg5 specifically in Paneth cells results in exaggerated intestinal inflammation characterized by complete destruction of the intestinal crypts resembling that seen in pan-epithelial Atg5-deficient mice. Additionally, lack of functional autophagy in Paneth cells within intestinal organoids and T. gondii-infected mice causes increased sensitivity to the proinflammatory cytokine TNF along with increased intestinal permeability, leading to exaggerated microbiota- and IFN-γ-dependent intestinal immunopathology. Thus, Atg5 expression in Paneth cells is essential for tissue protection against cytokine-mediated immunopathology during acute gastrointestinal infection.
staphylococcus aureus shifts toward commensalism in response to corynebacterium species
matthew m. ramsey, marcelo o. freire, rebecca a. gabrilska, kendra p. rumbaugh and katherine p. lemon 2016
dietary zinc alters the microbiota and decreases resistance to clostridium difficile infection
joseph p zackular et al. 2016
psychobiotics and the manipulation of bacteria-brain signals
sarkar et al. 2016
long-term effects on luminal and mucosal microbiota and commonly acquired taxa in faecal microbiota transplantation for recurrent clostridium difficile infection
jonna jalanka et al. 2016
Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). It restores the disrupted intestinal microbiota and subsequently suppresses C. difficile. The long-term stability of the intestinal microbiota and the recovery of mucosal microbiota, both of which have not been previously studied, are assessed herein. Further, the specific bacteria behind the treatment efficacy are also investigated.
We performed a high-throughput microbiota profiling using a phylogenetic microarray analysis of 131 faecal and mucosal samples from 14 rCDI patients pre- and post-FMT during a 1-year follow-up and 23 samples from the three universal donors over the same period.
The FMT treatment was successful in all patients. FMT reverted the patients’ bacterial community to become dominated by Clostridium clusters IV and XIVa, the major anaerobic bacterial groups of the healthy gut. In the mucosa, the amount of facultative anaerobes decreased, whereas Bacteroidetes increased. Post-FMT, the patients’ microbiota profiles were more similar to their own donors than what is generally observed for unrelated subjects and this striking similarity was retained throughout the 1-year follow-up. Furthermore, the universal donor approach allowed us to identify bacteria commonly established in all CDI patients and revealed a commonly acquired core microbiota consisting of 24 bacterial taxa.
FMT induces profound microbiota changes, therefore explaining the high clinical efficacy for rCDI. The identification of commonly acquired bacteria could lead to effective bacteriotherapeutic formulations. FMT can affect microbiota in the long-term and offers a means to modify it relatively permanently for the treatment of microbiota-associated diseases.
effect of oral capsule– vs colonoscopy-delivered fecal microbiota transplantation on recurrent clostridium difficile infection: a randomized clinical trial
dina kao et al. 2017
predators catalyze an increase in chloroviruses by foraging on the symbiotic hosts of zoochlorellae
john p. delong et al. 2017 al. 2016
Reproduction and growth of viruses depend on successful encounters with appropriate hosts. However, some hosts are difficult to encounter. In particular, chloroviruses cannot reach their target zoochlorellae hosts, because zoochlorellae are endosymbionts, living inside the cell of a protist that protects the zoochlorellae from the chlorovirus. The protist host is subject to predation, and we show that copepods foraging on zoochlorellae-bearing protists can disrupt the mutualism and pass endosymbiontic zoochlorellae through their guts, exposing them to chloroviruses. In this way, predators can catalyze the virus population growth by breaking down physical barriers between viruses and their endosymbiont hosts.
Virus population growth depends on contacts between viruses and their hosts. It is often unclear how sufficient contacts are made between viruses and their specific hosts to generate spikes in viral abundance. Here, we show that copepods, acting as predators, can bring aquatic viruses and their algal hosts into contact. Specifically, predation of the protist Paramecium bursaria by copepods resulted in a >100-fold increase in the number of chloroviruses in 1 d. Copepod predation can be seen as an ecological “catalyst” by increasing contacts between chloroviruses and their hosts, zoochlorellae (endosymbiotic algae that live within paramecia), thereby facilitating viral population growth. When feeding, copepods passed P. bursaria through their digestive tract only partially digested, releasing endosymbiotic algae that still supported viral reproduction and resulting in a virus population spike. A simple predator–prey model parameterized for copepods consuming protists generates cycle periods for viruses consistent with those observed in natural ponds. Food webs are replete with similar symbiotic organisms, and we suspect the predator catalyst mechanism is capable of generating blooms for other endosymbiont-targeting viruses.
deposition rates of viruses and bacteria above the atmospheric boundary layer
isabel reche et al. 2018