Commensal Microbial Communities Research Articles

Using Enteric Pathogens to Probe the Gut Microbiota

Enteric pathogens have evolved to manipulate the interface between the host and commensal microbial communities, making these pathogenic organisms superb research tools to interrogate the function of the gut microbiota during inflammatory flares. Here, we provide an overview of conceptual insights gained from experimental infection with enteric pathogens, such as Salmonella enterica serovar Typhimurium. Metabolic pathways at the host-microbe intersection will be a particular area of focus. A better understanding of the cellular and molecular mechanisms that control host-microbe interactions during episodes of inflammation may aid in the rational design of microbiota-targeting therapies.

The Human Microbiome and Child Growth - First 1000 Days and Beyond.

The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days - referring to the period from conception to 2 years of age - and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.

Pyrosequencing-based analysis of the complex microbiota located in the gastrointestinal tracts of growing-finishing pigs

The commensal gut microbial communities play an important role in the health and production efficiency of growing-finishing pigs. This study aimed to analyse the composition and diversity of the microbiota in the gastrointestinal tract sections (stomach, duodenum, jejunum, ileum, caecum, colon and rectum) of growing-finishing pigs. This analysis was assessed using 454 pyrosequencing targeting the V3–V6 region of the 16S rRNA gene. Samples were collected from 20, healthy pigs aged 24 weeks and weighing 115.9 ± 5.4 kg. The dominant bacterial phyla in the various gastrointestinal tract sections were Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. At the genus level, Prevotella, unclassified Lachnospiraceae, Ruminococcus, unclassified Ruminococcaceae and Oscillospira were more abundant in the large intestine than in the stomach and the small intestine. Unclassified Peptostreptococcaceae and Corynebacterium were more abundant in the small intestine than in the stomach and the large intestine. Shuttleworthia, unclassified Veillonellaceae and Mitsuokella were more abundant in the stomach than in the small and large intestines. At the species level, M. el.s.d.enii and M. multacida were predominant in the stomach. In addition, P. stercorea, P. copri, C. butyricum, R. flavefaciens and R. bromii were significantly more abundant in the large intestine than in the stomach and the small intestine. B. pseudolongum and B. thermacidophilum were significantly more abundant in the small intestine than in the stomach and the large intestine. Principal coordinates analysis showed that the overall composition of the pig gastrointestinal microbiota could be clustered into three groups: stomach, small intestine (duodenum, jejunum and ileum) and large intestine (caecum, colon and rectum). Venn diagrams illustrated the distribution of shared and specific operational taxonomic units among the various gastrointestinal tract sections.

Synbiotic approaches to human health and well-being.

SummarySynbiotics refer to combinations of probiotics and prebiotics that act synergistically to confer health benefits to the host. As a therapeutic strategy, they provide a gentle yet powerful method for modulating the composition and metabolic output of the human gut microbiota. In the context of achieving the UN Sustainable Development Goals, synbiotics have the potential to act as cost‐effective prophylactic measures against a variety of human ailments, ranging from infant diarrhoea to metabolic and inflammatory diseases in adults, by maintaining commensal microbial communities and metabolic networks that are conducive to human health.

Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury

BackgroundRecent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no...

Antimicrobial peptides extend lifespan in Drosophila.

Antimicrobial peptides (AMPs) are important defense molecules of the innate immune system. High levels of AMPs are induced in response to infections to fight pathogens, whereas moderate levels induced by metabolic stress are thought to shape commensal microbial communities at barrier tissues. We expressed single AMPs in adult flies either ubiquitously or in the gut by using the inducible GeneSwitch system to tightly regulate AMP expression. We found that activation of single AMPs, including Drosocin, resulted in a significant extension of Drosophila lifespan. These animals showed reduced activity of immune pathways over lifetime, less intestinal regenerative processes, reduced stress response and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin induction protected the animals against infections with the natural Drosophila pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented the lifespan extending effect of Drosocin. Our study provides new insights into the crosstalk of innate immunity, intestinal homeostasis and ageing.

Mucosal-associated invariant T cells respond to cutaneous microbiota

Abstract The microbiome consists of a diverse array of commensal microorganisms that reside at barrier sites of the body and promote immune homeostasis through the release of microbial products, including derivatives of vitamin synthesis. Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize vitamin B2 (riboflavin) derivatives presented by the major histocompatibility class I-like molecule, MR1. MAIT cells are predominantly located in barrier tissues, where they represent a substantial population of non-classical T cells and provide an initial defense to pathogens through their rapid production of either IL-17A or IFNg. However, it remains to be determined whether commensals regulate the development and function of MAIT cells. Here we show that MAIT cells are present in murine skin at a high frequency and their homeostasis requires the microbiota, as these lymphocytes are nearly absent in germ-free animals. Furthermore, application of distinct human commensal bacteria to the skin of mice induces the proliferation of IL-17A-producing MAIT cells that exhibit a unique transcriptional profile. The induction of these cells occurs in a manner that is partially dependent on both antigen presentation and IL-23 signaling. Additionally, MAIT cells stimulated by the cutaneous microbiota provide heterologous protection against subsequent pathogenic challenges. This work identifies MAIT cells as the only cell population that is entirely dependent on the microbiota and reveals the mechanism by which these cells respond to the commensal microbial community. Due to the high frequency of MAIT cells in human skin, these observations suggest that modulation of the skin-resident bacteria may have clinical applications.

The ecology of human microbiota: dynamics and diversity in health and disease.

Social welfare, better health care, and urbanization have greatly improved human health and well-being. On the other hand, Western societies suffer from the downsides of the elevated standard of living. Among other factors, the Western diet (poor in dietary fiber), lack of contact with natural biodiversity, and excessive antibiotic use are known to be associated with the increase in chronic inflammatory disorders. Limited exposure to microbial biodiversity, in combination with severe lifestyle-related disturbances to commensal microbial communities, especially during early life, is changing the diversity and composition of human microbiota. In this review, we try to promote and apply ecological theory to understand the dynamics and diversity of human commensal microbiota. In this context, we explore the changes in the microbiota that are relevant to human health, especially in light of the rise of chronic inflammatory disorders. We try to elucidate the underlying ecological mechanisms behind these disorders and provide potential solutions for their avoidance.

Long-term use of ceftriaxone sodium induced changes in gut microbiota and immune system

Antibiotic administration, while facilitating clearance of targeted infections, also perturbs commensal microbial communities. Previous studies have all focused on the effects of short term use of antibiotics. Here, we focus on the effects of long term use of antibiotic on gut microbiota and immunity. BALB/c mice received saline or different doses of ceftriaxone sodium (100, 200 and 400 mg/mL) via daily gavage for 150 days. Alterations of fecal microbiota, small intestine histopathology, body weight, spleen index, serum IgG, mucus SIgA, IFN-γ/IL-4 ratio, CD4/CD8 ratio and CD4+CD25+ cells were evaluated. Long term ceftriaxone sodium administration resulted in gut microbiota dysbiosis, intestine histological lesions, growth inhibition, spleen index reducing. The immune defense ability reduced as serum IgG and mucus SIgA decreased significantly. Not only the immune defense, long term ceftriaxone administration also affected immune regulation. The IFN-γ/IL-4 and CD4/CD8 ratios increased, the CD4+CD25+ cells reduced on days 30 and 60 after ceftriaxone administration. However, after 90 days of ceftriaxone administration, the IFN-γ/IL-4, CD4/CD8 ratios and CD4+CD25+ cells restored, which indicated a new balance of immune regulation had been formed. Overall, these findings contribute to our understanding of long term antibiotic administration influencing gut microbiota and immunity.

The Importance of Being Eubiotic

The human gut microbiota plays a very important part in the host’s life, being closely interconnected to its health. Upon birth, a well-balanced bacterial colonization of the infant gut has a profound impact on programming short and long term metabolic and immune homeostasis. Despite the fact that most of the causality is not yet fully understood, shift in the commensal gut microbial communities with implication to disease is often referred to as dysbiosis. Infants who tend to have a delayed and/or aberrant initial colonization with reduced microbial diversity and richness, whether induced by Caesarean section, premature delivery, or excessive use of perinatal antibiotics, could be more at risk for chronic health conditions associated with metabolic and immune disorders. Exploration of the long-term effects of this abnormal microbial number and diversity is critically needed in order to intervene early in the aberrant intestinal composition and restore numerous homeostatic systems (e.g. energy balance, glucose metabolism and immunity). Dietary manipulation of the gut microbiota through the so called ‘gut microbiota biomodulators’ (probiotics, prebiotics, synbiotics and postbiotics) represents a promising preventive avenue. This review aims to highlight factors that influence the gut microbiota soon after birth and discusses the potential gut-driven pathophysiologic pathways involved in intestinal dysbiosis and the gut microbiota-modulating effects of probiotics early in life.

Disturbance Regimes Predictably Alter Diversity in an Ecologically Complex Bacterial System.

ABSTRACTDiversity is often associated with the functional stability of ecological communities from microbes to macroorganisms. Understanding how diversity responds to environmental perturbations and the consequences of this relationship for ecosystem function are thus central challenges in microbial ecology. Unimodal diversity-disturbance relationships, in which maximum diversity occurs at intermediate levels of disturbance, have been predicted for ecosystems where life history tradeoffs separate organisms along a disturbance gradient. However, empirical support for such peaked relationships in macrosystems is mixed, and few studies have explored these relationships in microbial systems. Here we use complex microbial microcosm communities to systematically determine diversity-disturbance relationships over a range of disturbance regimes. We observed a reproducible switch between community states, which gave rise to transient diversity maxima when community states were forced to mix. Communities showed reduced compositional stability when diversity was highest. To further explore these dynamics, we formulated a simple model that reveals specific regimes under which diversity maxima are stable. Together, our results show how both unimodal and non-unimodal diversity-disturbance relationships can be observed as a system switches between two distinct microbial community states; this process likely occurs across a wide range of spatially and temporally heterogeneous microbial ecosystems.

Microbiome alterations in HIV infection a review.

Recent developments in molecular techniques have allowed researchers to identify previously uncultured organisms, which has propelled a vast expansion of our knowledge regarding our commensal microbiota. Interest in the microbiome specific to HIV grew from earlier findings suggesting that bacterial translocation from the intestines is the cause of persistent immune activation despite effective viral suppression with antiretroviral therapy (ART). Studies of SIV infected primates have demonstrated that Proteobacteria preferentially translocate and that mucosal immunity can be restored with probiotics. Pathogenic SIV infection results in a massive expansion of the virome, whereas non-pathogenic SIV infection does not. Human HIV infected cohorts have been shown to have microbiota distinctive from that of HIV negative controls and efforts to restore the intestinal microbiome via probiotics have often had positive results on host markers. The microbiota of the genital tract may play a significant role in acquisition and transmission of HIV. Modification of commensal microbial communities likely represents an important therapeutic adjunct to treatment of HIV. Here we review the literature regarding human microbiome in HIV infection.

Shaping of cutaneous function by encounters with commensals.

The skin is the largest organ in the human body and provides the first line of defence against environmental attack and pathogen invasion. It harbor multiple commensal microbial communities at different body sites, which play important roles in sensing the environment, protecting against colonization and infection of pathogens, and guiding the host immune system in response to foreign invasions. The skin microbiome is largely variable between individuals and body sites, with several core commensal members commonly shared among individuals at the healthy state. These microbial commensals are essential to skin health and can potentially lead to disease when their abundances and activities change due to alterations in the environment or in the host. While recent advances in sequencing technologies have enabled a large number of studies to characterize the taxonomic composition of the skin microbiome at various body sites and under different physiological conditions, we have limited understanding of the microbiome composition and dynamics at the strain level, which is highly important to many microbe-related diseases. Functional studies of the skin microbial communities and the interactions among community members and with the host are currently scant, warranting future investigations. In this review, we summarize the recent findings on the skin microbiome, highlighting the roles of the major commensals, including bacteria, fungi and bacteriophages, in modulating skin functions in health and disease. Functional studies of the skin microbiota at the metatranscriptomic and proteomic levels are also included to illustrate the interactions between the microbiota and the host skin.

Microbiota and arthritis: correlations or cause?

The microorganisms that colonise our bodies, the commensal 'microbiota', respond to changes in our behaviour and environment, and can also profoundly affect our health. We can now investigate these organisms with unprecedented depth and precision, revealing that they may contribute to the pathogenesis of diseases including arthritis. Here we discuss the changes occurring in the microbiota in people with arthritis, and how manipulation of the microbiota may provide an additional pathway for therapy. We highlight two important aspects of the recent literature. First we describe changes in the microbiota identified in people with arthritis; these correlations give insights into the microbial changes that may contribute to symptoms of arthritis. We then discuss attempts to ameliorate arthritis by manipulating the microbiota. This is a rapidly developing area of research. There are tantalising hints that interventions targeting the microbiota may become therapeutically viable for some types of inflammatory arthritis. Our commensal microbial communities respond to changes in our health, and are altered in people with arthritis. Understanding the complex relationships between the microbiota and the body may enable us to deliberately manipulate these organisms and provide additional therapeutic options for people with arthritis.

Adherent-invasive Escherichia coli Exacerbates Antibiotic-associated Intestinal Dysbiosis and Neutrophil Extracellular Trap Activation

Antibiotic-associated disruption of the gut microbiota is a known risk factor for Crohn's disease. This chronic inflammatory disorder results from aberrant host immune responses to subsets of the gut microbiota, and is characterized by intense neutrophil recruitment to the lamina propria, surface and crypt epithelium. Importantly, adherent-invasive Escherichia coli (AIEC) is abundant in ileal biopsies, highlighting a possible etiological role. In this study, we investigated the impact of antibiotics and AIEC challenge on murine intestinal dysbiosis and neutrophil extracellular trap activation, which is a critical component of the neutrophil antimicrobial repertoire. Male C57BL/6 mice were administered vancomycin and gentamicin (once daily, 3 days), and subsequently challenged with AIEC strain LF82 (once daily, 2 days). Perturbation of the gut microbiota was monitored using a combination of molecular and phylogenetic analyses. The impact of commensal and dysbiotic gut bacterial communities on neutrophil extracellular trap mobilization and intestinal redox balance was also quantified. Exposure of neutrophils to murine commensal gut microbial communities activated neutrophil extracellular trap formation. The capacity of neutrophils to cast these web-like structures was exacerbated following antibiotic and AIEC-associated intestinal dysbiosis, highlighting the possible overgrowth of immune-activating intestinal pathobionts. Intestinal dysbiosis was associated with an elevated capacity of the cultivated gut bacteria to produce reactive oxygen species in vitro, and increased colonic oxidative stress in vivo. Together, these data provide new insights into the detrimental effects of antibiotics on the gut microbiota, with clinically relevant implications for intestinal dysbiosis on neutrophil function and intestinal redox balance.

The Brain-Body-Microbial Communities: A Crosstalk and Stress Exchange Beyond the “Gut hypothesis”

For many decades, the consequences of “stress” have been perceived as a “unidirectional” pathway where some stressful life conditions cause “mental stress” that activates the brain’s stress response systems, which sequentially affect many of the major body systems especially gastrointestinal tract. The striking upsurge in incidence of neuropsychiatric and neurodevelopmental disorders, in the last five decades, appeals to a crucial “bidirectional” interaction between the nervous system with other body systems. Such fast expansion of these disorders enforces also a causal role for environmental insults inflicted by the changing ecosystems as well as the modernization of human life style including lavish use of antibiotics, high hygiene standards and predominant utilization of urban western diet. It is also becoming clear that several neurological and psychiatric disorders are more and more being linked to a wide range of systemic dysfunctions including, most notably, immunological impairments and microbial manipulation. We believe that nervous system development and function are not only highly coupled with other physiological body systems but also with non-physiologic microenvironments created by pathogenic agents or dormant commensals. Direct or bystander effects of certain infectious agents or complex microbiome communities on brain development and function could modulate and evoke deviated behavioral responses and abnormal psychological outcomes. We think a better understanding of the basic components of this bidirectional interaction and the comprehensive characterization of the involved pathways will produce significant insights into the way nervous system diseases evolve and yield a novel array of therapeutic strategies. Here, we discuss different aspects of the dynamic crosstalk between the nervous system and microenvironments created by long-lasting pathogenic infections or by permanent commensal microbial communities. To pursue this goal, we review hypotheses and evidences that link certain pathogens or microbiome compositions to the development of neuropsychiatric diseases and/or neurodevelopmental disorders in genetically predisposed persons.

Antibiotic Treatment Affects Intestinal Permeability and Gut Microbial Composition in Wistar Rats Dependent on Antibiotic Class.

Antibiotics are frequently administered orally to treat bacterial infections not necessarily related to the gastrointestinal system. This has adverse effects on the commensal gut microbial community, as it disrupts the intricate balance between specific bacterial groups within this ecosystem, potentially leading to dysbiosis. We hypothesized that modulation of community composition and function induced by antibiotics affects intestinal integrity depending on the antibiotic administered. To address this a total of 60 Wistar rats (housed in pairs with 6 cages per group) were dosed by oral gavage with either amoxicillin (AMX), cefotaxime (CTX), vancomycin (VAN), metronidazole (MTZ), or water (CON) daily for 10–11 days. Bacterial composition, alpha diversity and caecum short chain fatty acid levels were significantly affected by AMX, CTX and VAN, and varied among antibiotic treatments. A general decrease in diversity and an increase in the relative abundance of Proteobacteria was observed for all three antibiotics. Additionally, the relative abundance of Bifidobacteriaceae was increased in the CTX group and both Lactobacillaceae and Verrucomicrobiaceae were increased in the VAN group compared to the CON group. No changes in microbiota composition or function were observed following MTZ treatment. Intestinal permeability to 4 kDa FITC-dextran decreased after CTX and VAN treatment and increased following MTZ treatment. Plasma haptoglobin levels were increased by both AMX and CTX but no changes in expression of host tight junction genes were found in any treatment group. A strong correlation between the level of caecal succinate, the relative abundance of Clostridiaceae 1 family in the caecum, and the level of acute phase protein haptoglobin in blood plasma was observed. In conclusion, antibiotic-induced changes in microbiota may be linked to alterations in intestinal permeability, although the specific interactions remain to be elucidated as changes in permeability did not always result from major changes in microbiota and vice versa.

Aflatoxin B1 Induced Compositional Changes in Gut Microbial Communities of Male F344 Rats.

Aflatoxins are a group of potent foodborne toxicants naturally occurring in maize and groundnuts. Differential species-specific sensitivity to aflatoxins has been documented but cannot be fully explained by the differences in metabolism of these toxicants among animal species. Commensal microbial communities (microbiota) are critical to human and animal health, but few studies have assessed interactions between xenobiotic toxins and those microbiota, and its potential effects to humans and animals. Here, an exploratory dosing experiment was conducted to explore effects of Aflatoxin B1 (AFB1) on the gut microbiota in a commonly used rat model. Male F344 rats were randomly divided into groups and treated with different concentrations of AFB1. Microbial communities in fecal samples were assessed using 16S rRNA sequence analysis. We found that samples from the control group had a phylogenetically diverse community, and that increasing AFB1 doses decreased this diversity but increased evenness of community composition. In addition, the gut microbiota from different samples was clustered according to their dosing regimens. There is no community shift at the phylum level but some lactic acid bacteria were significantly depleted by AFB1. These findings suggested that AFB1 could modify the gut microbiota in a dose-dependent manner.

ID: 14: Immune regulation at barrier surfaces

Employing models of microbial colonization, pathogen infection, chronic inflammation and tissue repair, research in the Artis lab is examining how mammalian host genetics and signals derived from the environment and commensal microbial communities influence innate and adaptive immune cell responses. We are employing gnotobiotic mice to examine the influence of defined commensal microbial communities on intestinal and peripheral immune cell development, function and influence on tissue homeostasis. Our recent findings indicate that commensal microbes have a significant regulatory influence on lymphocyte, innate lymphoid cell and granulocyte function associated with susceptibility to multiple infectious, inflammatory and metabolic disease processes. It is hoped that the results of these studies will advance understanding of the pathophysiology of multiple chronic inflammatory diseases, including asthma, allergy, inflammatory bowel disease and obesity, and provide a framework to test new therapeutic pathways to prevent and treat these diseases.

A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease

ABSTRACTObesity is a strong predictive factor in the development of chronic disease and has now superseded undernutrition as a major public health issue. Chronic inflammation is one mechanism thought to link excess body weight with disease. Increasingly, the gut and its extensive population of commensal microflora are recognized as playing an important role in the development of obesity-related chronic inflammation. Obesity and a high fat diet are associated with altered commensal microbial communities and increased intestinal permeability which contributes to systemic inflammation as a result of the translocation of lipopolysaccharide into the circulation and metabolic endotoxemia. Various milk proteins are showing promise in the prevention and treatment of obesity and chronic low-grade inflammation via reductions in visceral fat, neutralization of bacteria at the mucosa and reduced intestinal permeability. In this review, we focus on evidence supporting the potential antiobesogenic and anti-inflammatory effects of bovine whey-derived lactoferrin and immunoglobulins.