Impact Of Intestinal Microbiota Research Articles

Characterization of the intestinal microbiota in MSM with HIV infection

BackgroundHIV-infected persons demonstrate notable disturbances in their intestinal microbiota; however, the impact of intestinal microbiota on HIV susceptibility in men who have sex with men (MSM), as well as the effects of HIV and antiretroviral therapy (ART) on their gut microbiota, remains under active study. Thus, our research focuses on clarifying the distinctions in intestinal microbiota composition among uninfected MSM and non-MSM healthy controls, investigating the alterations in early-stage intestinal microbial communities following HIV infection, and assessing how ART affects the intestinal microbiota.MethodsThis study enrolled four participant groups: uninfected MSM, Recent HIV-1 infection (RHI) MSM, MSM on ART, and non-MSM healthy controls, with 30 individuals in each group. We utilized 16S ribosomal DNA (16S rDNA) amplicon sequencing to analyze fecal microbiota and employed Luminex multiplex assays to measure plasma markers for microbial translocation (LBP, sCD14) and the inflammatory marker CRP.FindingsComparing uninfected MSM to non-MSM healthy controls, no substantial variances were observed in α and β diversity. Uninfected MSM had higher average relative abundances of Bacteroidetes, Prevotella, and Alloprevotella, while Bacteroides, Firmicutes, and Faecalibacterium had lower average relative abundances. MSM on ART had lower intestinal microbiota diversity than RHI MSM and uninfected MSM. In MSM on ART, Megasphaera and Fusobacterium increased, while Faecalibacterium and Roseburia decreased at genus level. Additionally, treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) led to significant alterations in intestinal microbiota diversity and composition compared to RHI MSM. The random forest model showed that HIV infection biomarkers effectively distinguished between newly diagnosed HIV-infected MSM and HIV-negative MSM, with an ROC AUC of 76.24% (95% CI: 61.17-91.31%).ConclusionsMSM showed early intestinal microbiota imbalances after new HIV infection. MSM on ART experienced worsened dysbiosis, indicating a combined effect of HIV and ART. NNRTI-based treatment notably changed intestinal microbiota, suggesting a potential direct impact of NNRTI drugs on intestinal microbiota.

Research progress on intestinal microbiota regulating cognitive function through the gut-brain axis.

The intestinal microbiota community is a fundamental component of the human body and plays a significant regulatory role in maintaining overall health and in the management disease states.The intestinal microbiota-gut-brain axis represents a vital connection in the cognitive regulation of the central nervous system by the intestinal microbiota.The impact of intestinal microbiota on cognitive function is hypothesized to manifest through both the nervous system and circulatory system. Imbalances in intestinal microbiota during the perioperative period could potentially contribute to perioperative neurocognitive dysfunction. This article concentrates on a review of existing literature to explore the potential influence of intestinal microbiota on brain and cognitive functions via the nervous and circulatory systems.Additionally, it summarizes recent findings on the impact of perioperative intestinal dysbacteriosis on perioperative neurocognitive dysfunction and suggests novel approaches for prevention and treatment of this condition.

Heat-inactivated Bifidobacterium adolescentis ameliorates colon senescence through Paneth-like-cell-mediated stem cell activation

Declined numbers and weakened functions of intestinal stem cells (ISCs) impair the integrity of the intestinal epithelium during aging. However, the impact of intestinal microbiota on ISCs in this process is unclear. Here, using premature aging mice (telomerase RNA component knockout, Terc−/−), natural aging mice, and in vitro colonoid models, we explore how heat-inactivated Bifidobacterium adolescentis (B. adolescentis) affects colon senescence. We find that B. adolescentis could mitigate colonic senescence-related changes by enhancing intestinal integrity and stimulating the regeneration of Lgr5+ ISCs via Wnt/β-catenin signaling. Furthermore, we uncover the involvement of Paneth-like cells (PLCs) within the colonic stem-cell-supporting niche in the B. adolescentis-induced ISC regeneration. In addition, we identify soluble polysaccharides (SPS) as potential effective components of B. adolescentis. Overall, our findings reveal the role of heat-inactivated B. adolescentis in maintaining the ISCs regeneration and intestinal barrier, and propose a microbiota target for ameliorating colon senescence.

Impact of Intestinal Microbiota on Growth Performance of Suckling and Weaned Piglets.

Small-scale studies investigating the relationship between pigs' intestinal microbiota and growth performance have generated inconsistent results. We hypothesized that on farms under favorable environmental conditions (e.g., promoting sow nest-building behavior, high colostrum production, low incidence of diseases and minimal use of antimicrobials), the piglet gut microbiota may develop toward a population that promotes growth and reduces pathogenic bacteria. Using 16S rRNA gene amplicon sequencing, we sampled and profiled the fecal microbiota from 170 individual piglets throughout suckling and postweaning periods (in total 670 samples) to track gut microbiota development and its potential association with growth. During the suckling period, the dominant genera were Lactobacillus and Bacteroides, the latter being gradually replaced by Clostridium sensu scricto 1 as piglets aged. The gut microbiota during the nursery stage, not the suckling period, predicted the average daily growth (ADG) of piglets. The relative abundances of SCFA-producing genera, in particular Faecalibacterium, Megasphaera, Mitsuokella, and Subdoligranulum, significantly correlated with high ADG of weaned piglets. In addition, the succession of the gut microbiota in high-ADG piglets occurred faster and stabilized sooner upon weaning, whereas the gut microbiota of low-ADG piglets continued to mature after weaning. Overall, our findings suggest that weaning is the major driver of gut microbiota variation in piglets with different levels of overall growth performance. This calls for further research to verify if promotion of specific gut microbiota, identified here at weaning transition, is beneficial for piglet growth. IMPORTANCE The relationship between pigs' intestinal microbiota and growth performance is of great importance for improving piglets' health and reducing antimicrobial use. We found that gut microbiota variation is significantly associated with growth during weaning and the early nursery period. Importantly, transitions toward a mature gut microbiota enriched with fiber-degrading bacteria mostly complete upon weaning in piglets with better growth. Postponing the weaning age may therefore favor the development of fiber degrading gut bacteria, conferring the necessary capacity to digest and harvest solid postweaning feed. The bacterial taxa associated with piglet growth identified herein hold potential to improve piglet growth and health.

Impact of intestinal microbiota on metabolic toxicity and potential detoxification of amygdalin.

Amygdalin (Amy) is metabolized into cyanide in vivo, which may lead to fatal poisoning after oral administration. The defense mechanisms against toxic cyanide have not yet been adequately studied. In this study, comparative toxicokinetics study of Amy was performed in normal and pseudo germ-free rats. The efficiency of cyanide release was significant higher in normal group when given a single oral dose of 440 mg/kg (50% median lethal dose). Thiocyanate, the detoxification metabolite, was firstly detected in feces, caecum, and intestinal microbiota incubation enzymic system. The results suggest intestinal microbiota is involved in bidirectional regulation of toxicity and detoxification of Amy. We further identified the species related to cyanogenesis of Amy with metagenomic sequencing, such as Bifidobacterium pseudolongum, Marvinbryantia formatexigens, and Bacteroides fragilis. Functional analysis of microbiota reveals the detoxification potential of intestinal microbiota for cyanide. Sulfurtransferase superfamily, such as rhodanese, considered as main detoxification enzymes for cyanide, are largely found in Coriobacteriaceae bacterium, Butyricicoccus porcorum, Akkermansia muciniphila, etc. Besides, cyanoamino acid metabolism pathway dominated by Escherichia coli may contribute to the detoxification metabolism of cyanide. In summary, intestinal microbiota may be the first line of defense against the toxicity induced by Amy.

Impact of Intestinal Microbiota on Cognitive Flexibility by a Novel Touch Screen Operant System Task in Mice.

Cognitive flexibility is the ability to rapidly adapt to a constantly changing environment. It is impaired by aging as well as in various neurological diseases, including dementia and mild cognitive impairment. In rodents, although many behavioral test protocols have been reported to assess learning and memory dysfunction, few protocols address cognitive flexibility. In this study, we developed a novel cognitive flexibility test protocol using touch screen operant system. This test comprises a behavioral sequencing task, in which mice are required to discriminate between the “rewarded” and “never-rewarded” spots and shuttle between the two distantly positioned rewarded spots, and serial reversals, in which the diagonal spatial patterns of rewarded and never-rewarded spots were reversely changed repetitively. Using this test protocol, we demonstrated that dysbiosis treated using streptomycin induces a decline in cognitive flexibility, including perseveration and persistence. The relative abundances of Firmicutes and Bacteroides were lower and higher, respectively, in the streptomycin-treated mice with less cognitive flexibility than in the control mice. This is the first report to directly show that intestinal microbiota affects cognitive flexibility.

Impact of Intestinal Microbiota on Quality of Life (QoL) of Hemodialysis Patients

Chronic kidney disease is a global problem. Increasing evidence suggests that interstinal microflore is altered in patients with Chronic Kidney Disease (CKD).The gut microbiome is a key driver of chronic inflammation. Many of uremic retention solutes are produced by dysbiotic intestinal microflore that may have a great impact on survival of the CKD patients. Our sample study consisted of 147 patients (78 female, 69 male age 18-75) undergoing hemodialysis in one dialysis center. Data were collected by the completion of a scpecially designed questionnaire. Patients received hemodialysis therapy for 4-5 hours sessions, three times weekly using polysulfone dialyzers. It was revealed significant alteration of the colonic bacterial flora in hemodialysis patients, with the excess of the uremic toxin producing bacteria. Also, there was strict correlation between gut dysbiosis and HD patent's QoL.

Impact of Intestinal Microbiota on Quality of Life (QoL) of Hemodialysis Patients

Chronic kidney disease is a global problem. Increasing evidence suggests that interstinal microflore is altered in patients with Chronic Kidney Disease (CKD).The gut microbiome is a key driver of chronic inflammation. Many of uremic retention solutes are produced by dysbiotic intestinal microflore that may have a great impact on survival of the CKD patients. Our sample study consisted of 147 patients (78 female, 69 male age 18-75) undergoing hemodialysis in one dialysis center. Data were collected by the completion of a scpecially designed questionnaire. Patients received hemodialysis therapy for 4-5 hours sessions, three times weekly using polysulfone dialyzers. It was revealed significant alteration of the colonic bacterial flora in hemodialysis patients, with the excess of the uremic toxin producing bacteria. Also, there was strict correlation between gut dysbiosis and HD patent's QoL.

Impact of Intestinal Microbiota on Growth and Feed Efficiency in Pigs: A Review.

This review summarises the evidence for a link between the porcine intestinal microbiota and growth and feed efficiency (FE), and suggests microbiota-targeted strategies to improve productivity. However, there are challenges in identifying reliable microbial predictors of host phenotype; environmental factors impact the microbe–host interplay, sequential differences along the intestine result in segment-specific FE- and growth-associated taxa/functionality, and it is often difficult to distinguish cause and effect. However, bacterial taxa involved in nutrient processing and energy harvest, and those with anti-inflammatory effects, are consistently linked with improved productivity. In particular, evidence is emerging for an association of Treponema and methanogens such as Methanobrevibacter in the small and large intestines and Lactobacillus in the large intestine with a leaner phenotype and/or improved FE. Bacterial carbohydrate and/or lipid metabolism pathways are also generally enriched in the large intestine of leaner pigs and/or those with better growth/FE. Possible microbial signalling routes linked to superior growth and FE include increased intestinal propionate production and reduced inflammatory response. In summary, the bacterial taxa and/or metabolic pathways identified here could be used as biomarkers for FE/growth in pigs, the taxa exploited as probiotics or the taxa/functionality manipulated via dietary/breeding strategies in order to improve productivity in pigs.

The impact of intestinal microbiota on weight loss in Parkinson's disease patients: a pilot study.

Background: There is increasing evidence of the association between microbiome dysfunction and Parkinson's disease (PD). Moreover, some PD patients suffer from unintentional weight loss (WL) which may precede the motor manifestations of the disease. Materials & methods: Gut microbiota profiling by 16S rRNA gene sequencing was performed in PD patients with an unintended WL, in steady weight patients (non-WL [NWL]) and in matched normal subjects. KEGG functional predictions were carried out. Results: Microbiota profiles revealed a dissimilarity between WL and NWL. Moreover, WL pathways were characterized by fatty acid biosynthesis, while NWL by inflammation pathways. Conclusion: The gut microbiota could participate in weight alteration observed in PD by the presence of bacteria involved in weight gain and inflammation, or conversely by bacteria implicated in energy expenditure.

Influence of gut microbiota on mucosal IgA antibody response to the polio vaccine

The impact of intestinal microbiota on mucosal antibody response to the polio vaccine is poorly understood. We examined changes in vaccine-induced intestinal mucosal immunity to poliovirus by measuring the immunoglobulin A (IgA) antibody levels in stool samples collected from 107 infants in China, and the samples were collected 14 days after different sequential vaccinations combining inactivated polio vaccine (IPV) with oral poliovirus vaccine (OPV). Gut microbiota were identified using 16S ribosomal RNA sequencing 28 days before, 14 days before, and at the last dose of OPV. Vaccine-induced type 2-specific mucosal IgA showed a decrease after switching from trivalent to bivalent OPV (bOPV) (positive rate of polio type 2-specific mucosal IgA, 16.7%, 11.8%, and 45.9% for IPV + 2bOPV, 2IPV + bOPV, and 2IPV + trivalent OPV groups, respectively). The composition of the gut microbiome was significantly different, a higher abundance of Firmicutes and a lower abundance of Actinobacteria were observed in IgA-negative infant (n = 66) compared with IgA-positive infants (n = 39), and the gut microbiota were more diverse in IgA-negative infants on the day of OPV inoculation. The abundance of Clostridia was concomitant with a significantly lower conversion rate of mucosal IgA responses to the polio vaccine. The composition of the gut microbiome may affect the intestinal mucosal IgA response to the polio vaccine.

Making Progress in Graft-Versus-Host Disease Prophylaxis and Microbiome Analysis in the Blood and Marrow Transplant Clinical Trials Network: Progress III (1703)/MI-Immune (1801)

Graft-versus-host disease (GVHD) remains the major source of morbidity and transplant-related mortality after allogeneic hematopoietic cell transplant (alloHCT). Since the mid-1980s, the standard prophylaxis for GVHD has been a calcineurin inhibitor plus methotrexate (MTX). Subsequent clinical trials designed to intensify GVHD prophylaxis have shown an increased risk of relapse, thus negating survival benefit. The ideal GVHD prophylaxis regimen is therefore associated with a high graft-versus-host disease-free, relapse-free survival (GRFS), a composite endpoint that reflects survival without morbidity. A recent 3-arm randomized phase II study conducted through the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1203) showed a benefit in GRFS using post-transplant cyclophosphamide, tacrolimus, and mycophenolate mofetil (PTCy/Tac/MMF) with a hazard ratio of 0.72 (90% confidence interval 0.54 - 0.94, p-0.044) compared to contemporary non-randomized CIBMTR Tac/MTX controls. Based upon these results, the BMT CTN has launched 1703, a multicenter randomized phase III study of standard Tac/MTX vs PTCy/Tac/MMF in the setting of reduced intensity conditioning, matched peripheral blood stem cell transplantation (RIC PBSCT). The primary endpoint of 1703 is GRFS at 1 year, and several secondary endpoints, including patient-reported outcomes, will be analyzed. A series of recent, predominantly single-center studies have shown an association with the composition of intestinal microbiota and the development of acute GVHD, which suggests that this may be a potential modifiable biomarker of disease. The generalizability of findings from these studies is yet unknown, and no large multi-center studies on the intestinal microbiota of HCT patients has yet been carried out. Patients enrolled in 1703 will be eligible to co-enroll in BMT CTN 1801, the Mi-Immune study, detailing microbiota and immune reconstitution in this cohort. The primary endpoint of 1801 is 1-year non-relapse mortality by tertiles of stool microbial diversity at engraftment. Secondary objectives, including effect of GVHD prophylaxis on diversity, oligodomination and risk of bloodstream infection, volume of antimicrobial exposure, and T-cell receptor diversity, will be analyzed. The combined studies of BMT CTN 1703/1801 will define the standard of care for GVHD prophylaxis in the RIC PBSCT setting and vastly expand our knowledge on the impact of intestinal microbiota in critical outcomes after alloHCT. This clinical trial is registered at ClinicalTrials.gov NCT03959241. Figure Disclosures Holtan: Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Janssen: Consultancy; CSL Behring: Consultancy. Bhatt:ArcBio: Other: Scientific Advisory Board; January.ai: Other: Scientific Advisory Board; Caribou Bioscience: Other: Scientific Advisory Board; Kaleido Biosciences: Consultancy, Other: Paid Consultant; Janssen Human Microbiome Institute: Consultancy, Other: Paid Consultant; Illumina: Honoraria; 10x Genomics: Other: Research collaboration without funding support; Illumina: Other: Research collaboration without funding support; Agilent: Research Funding; Global Oncology, Inc: Other: Nonprofit Board. Perales:Bellicum: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; MolMed: Membership on an entity's Board of Directors or advisory committees; NexImmune: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Omeros: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria; Medigene: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Kyte/Gilead: Research Funding; Miltenyi: Research Funding; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nektar Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kean:HiFiBio: Consultancy; BlueBirdBio: Research Funding; Gilead: Research Funding; Regeneron: Research Funding; EMDSerono: Consultancy; FortySeven: Consultancy; Magenta: Research Funding; Kymab: Consultancy; Jazz: Research Funding; Bristol Meyers Squibb: Patents & Royalties, Research Funding. Hamadani:Medimmune: Consultancy, Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Merck: Research Funding; Celgene: Consultancy; Otsuka: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Sanofi Genzyme: Research Funding, Speakers Bureau. Bolaños-Meade:Incyte Corporation: Other: DSMB fees.

Development of an Infection Risk Index for Microbiome Targeted Intervention in Children at High-Risk of Multidrug-Resistant Bloodstream Infections

Background Bloodstream infections (BSI) cause significant morbidity and mortality following pediatric hematopoietic stem cell transplantation (HSCT) and are increasingly from multidrug-resistant pathogens. Most of these BSI pathogens arise from the intestines. Increased evidence demonstrates commensal gut anaerobes maintain host resistance from enteric infection, while loss of commensals increases host susceptibility. Antibiotic use reduces gut anaerobes and allows a compensatory increased pathogen burden that precedes BSI; BSI risk is related to colonization burden. Recent reports suggest fecal microbiota transplantation (FMT) can displace an enteric pathogens and broad-spectrum antibiotic resistance genes during restoration of a healthy microbiome. However, the impact of intestinal microbiota on colonization, transmission, and invasive MDR infections is poorly understood in children undergoing HSCT. Methods Using metagenomic shotgun sequencing (MSS) data of longitudinal stool samples from high-risk children, including 63 undergoing HSCT with 166 samples preceding BSI onset (n = 23), we developed a metagenomic-based infection risk index (IRI) from key microbiome features (scaled Brady-Curtis distance relative to healthy controls and relative anaerobe and pathogen abundance). Traditional cart data analysis was compared to advanced machine learning algorithms that consider microbiome distribution, longitudinal sampling, and feature selection. Results A metagenomic-derived IRI from our cohort identified children having up to an 8-fold increased BSI risk. Evaluation of these key microbiome features as a diagnostic screening test by traditional cart analysis accurately identified patients at-risk for BSI with 91% sensitivity using its negative likelihood ratio. However, its specificity of 51% prohibits targeting interventions to those at greatest risk (Figure 1). Therefore, advanced machine learning algorithms were used for metagenomic-derived BSI prediction. While training results suggest overfitting, its performance promises clinical utility with a sensitivity of 92% and specificity of 84% warranting optimization and validation in HSCT patients (Figure 2). Analysis during heterologous FMT interventions in 5 symptomatic high-risk children (including 1 HSCT patient) revealed a concomitant pathogen-dominated gut microbiome harboring a high burden of broad-spectrum antibiotic resistance genes prior to each FMT. Following FMT, we confirmed restoration of a healthy gut microbiome with abundant anaerobes had a low metagenomic-derived IRI in all cases (Figure 3). Conclusions The application of advanced machine learning to shotgun metagenomic data provides the resolution required for accurate BSI prediction to identify HSCT patients at greatest risk preceding an illness providing new opportunity for early FMT intervention to prevent BSI.

Impact of Intestinal Microbiota on Reconstitution of Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Stem Cell Transplantation

INTRODUCTION:Mucosal-associated invariant T (MAIT) cells are innate-like T cells that express a semi-invariant T cell receptor (TCR) consisting of a Vα7.2 chain paired with a restricted repertoire of Vβ chains. The MAIT cell TCR recognizes riboflavin metabolites, and potentially other ligands produced by distinct bacterial and fungal species and presented in the context of the MHC class I-related molecule (MR1). MAIT cells are abundant in humans, comprising up to 10% of T cells in the peripheral blood, and are enriched in the gastrointestinal (GI) mucosa and liver. The GI localization of MAIT cells and their activation by microbial metabolites raises the possibility of a role in acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (HCT) when the GI mucosal barrier is compromised. Indeed, we found an increased risk of severe aGVHD in patients with low MAIT cell counts in the blood after HCT (Bhattacharyya, BBMT 2018). The impact of alterations in the GI microbiota on reconstitution and function of MAIT cells in HCT recipients remains unknown.METHODS:Paired blood and stool samples were collected from allogeneic HCT recipients prior to conditioning, and on days 0, 10, 20, 30, 60, and 100 after HCT. MAIT cells were identified as CD3+/CD161hi/Vα7.2+ cells by flow cytometry and absolute counts in the peripheral blood were determined in conjunction with a complete blood count. The bacterial composition of the stool was characterized by broad-range 16S ribosomal RNA gene PCR and high-throughput sequencing followed by placement into a maximum-likelihood phylogeny via pplacer against a custom reference package. A linear mixed model with random intercept was used to estimate the correlation between absolute MAIT cell count in the blood and relative abundance of bacterial species in the stool.RESULTS:We analyzed 302 paired blood and stool samples from 78 allogeneic HCT recipients. MAIT cells declined from pre-conditioning levels to a nadir on the day of stem cell infusion, followed by an increase to a plateau between day 30 and 100 after HCT. Microbial diversity was low prior to HCT and further decreased in the first 20 days after HCT, followed by an increase between days 30 and 100 to pre-HCT levels. MAIT cell counts in the blood correlated with stool microbial diversity and the relative abundance of individual bacterial species. We found a direct correlation between the abundance of bacterial species belonging to the Lachnospiraceae family (including distinct Blautia and Clostridium spp.) and an inverse correlation between the relative abundance of oral and perineal bacteria in the stool with absolute MAIT cell counts in blood (Table 1). Consistent with our findings and a possible protective role for MAIT cells in the pathogenesis of aGVHD (Varelias, JCI 2018), decreased Blautia abundance in stool has been associated with increased risk of death from aGVHD (Jenq, BBMT 2015) and increased abundance of oral and perineal bacteria in stool has been associated with aGVHD (Golob, CID 2017).CONCLUSION:In this study, we identified bacterial species whose relative abundance directly or inversely correlated with the absolute number of MAIT cells in blood after HCT. This observation is consistent with a mechanism in which a gut microbiome that is deficient in bacteria in the Lachnospiraceae family (capable of generating riboflavin metabolites for MAIT cell activation) is associated with poor MAIT cell recovery and potentially an increased risk of aGVHD. [Display omitted] DisclosuresTurtle:Caribou Biosciences: Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Nektar Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno/Celgene: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.

Microbiota-Dependent Involvement of Th17 Cells in Murine Models of Inflammatory Arthritis.

ObjectiveIntestinal microbiota are associated with the development of inflammatory arthritis. The aim of this study was to dissect intestinal mucosal immune responses in the preclinical phase of arthritis and determine whether the presence of Th17 cells, beyond involvement of the cytokine interleukin‐17 (IL‐17), is required for arthritis development, and whether the involvement of Th17 cells in arthritis depends on the composition of the host microbiota.MethodsMucosal T cell production of IL‐17, interferon‐γ, tumor necrosis factor α (TNFα), IL‐22, and granulocyte–macrophage colony‐stimulating factor (GM‐CSF) was analyzed by flow cytometry and Luminex assay before arthritis onset in mice immunized to develop collagen‐induced arthritis (CIA). Pathogenic features of arthritis in mice with CIA and mice with antigen‐induced arthritis were compared between Th17 cell–deficient (CD4‐Cre + Rorc flox/flox) and Th17 cell–sufficient (CD4‐Cre − Rorc flox/flox) mice. In addition, the impact of intestinal microbiota on the Th17 cell dependence of CIA was assessed.ResultsLamina propria CD4 T cells were activated before the onset of arthritis in mice with CIA, with marked up‐regulation of several cytokines, including IL‐17A, TNFα, and GM‐CSF. CD4‐Cre + Rorc flox/flox mice showed a specific reduction in intestinal mucosal levels of Th17 cells and partially reduced levels of IL‐17–producing CD8 T cells. However, total levels of IL‐17A, mostly produced by γδ T cells and neutrophils, were unaffected. The severity of arthritis was significantly reduced in Th17 cell–deficient mice, suggesting that Th17 cells have additional, IL‐17A–independent roles in inflammatory arthritis. Accordingly, antigen‐stimulated T cells from Th17 cell–deficient mice produced less IL‐17A, IL‐17F, and GM‐CSF. Importantly, the dependence of CIA on the involvement of Th17 cells was mitigated in the presence of an alternative microbiome.ConclusionThese data from murine models suggest that activation of mucosal immunity precedes the development of arthritis, and also that Th17 cells have a microbiota‐dependent role in arthritis. Therefore, a microbiome‐guided stratification of patients might improve the efficacy of Th17‐targeted therapies.

Gut microbiota: puppeteer of the host juvenile growth.

This review focuses on the recent discoveries about the impact of intestinal microbiota on mammalian host juvenile growth. Intestinal microbiota is a powerful modulator of many facets of multicellular host's physiology. Recent results from human field studies and animal research have clearly shown that not only the nutrition, but also the intestinal microbiota impacts host postnatal growth kinetics. Absence of microbiome leads to stunted growth in mammalian gnotobiotic models and changes in the composition of the intestinal microbiota can impact the postnatal growth kinetics both positively and negatively under normal nutritional conditions as well as in undernutrition. Strikingly, specific bacterial strains are able to interact with GH/IGF-1 somatotropic axis activity, thus directly impacting host juvenile development. Intestinal microbiota dictates the pace of host postnatal growth. This newly described role envisages that therapy with specific bacterial strains, together with re-nutritional strategies, might successfully alleviate the long-term sequelae of undernutrition during childhood in humans.

The impact of intestinal microbiota on bio-medical research: definitions, techniques and physiology of a "new frontier".

In recent years the metagenomics techniques have allowed to study composition and function of the intestinal microbiota. The microbiota is a new frontier of biomedical research to be explored and there is growing evidence of its fundamental health-promoting activity. The present review gives a synthetic overview on the characteristics and the role of the microbiota in the adult with particular reference to physiology, pathophysiology and relationships with the host and the environment. (www.actabiomedica.it)

Insights into the fecal microbiota of captive Iberian lynx (Lynx pardinus).

The Iberian lynx (Lynx pardinus) is an endangered species restricted to several areas of Spain and Portugal. Its low genetic diversity likely provokes immune depression and high susceptibility to infectious diseases. The intestinal microbiota is closely related to host health and nutrition. In order to contribute to the knowledge of the Iberian lynx intestinal microbiota, fecal microbiota of captive specimens from two breeding centers ("La Olivilla" and "El Acebuche"), located in Southern Spain, were studied by Denaturing Gradient Gel Electrophoresis (DGGE). Results grouped microbiota in two main clusters (I and III) which included DGGE patterns of 19 out of 36 specimens, cluster I being the most frequent in "La Olivilla" (50%) and cluster III in "El Acebuche" (55.55 %) specimens. Bacteroidetes, Firmicutes and Proteobacteria phyla were identified. Segregation of clusters I and III was attributed to different microorganism presence (Pseudomonas koreensis, Pseudomonas migulae, Carnobacterium sp., Arthrobacter, Robinsoniella peorensis and Ornithinibacillus sp.) and ability to use different carbon sources. Biolog EcoPlates® results indicate high functional diversity of fecal microbiota, it being higher in cluster III. The great impact of intestinal microbiota on host health supports the importance of its microbial composition understanding. This study is the first report of captive Iberian lynx fecal microbiota composition. [Int Microbiol 20(1): 31-41 (2017)].

Impact of intestinal microbiota and gastrointestinal conditions on the in vitro survival and growth of Bacillus cereus

Ingestion of B. cereus can result in diarrhea, if these bacteria survive gastrointestinal passage and achieve growth and enterotoxin production in the small intestine. The gastrointestinal survival of vegetative cells and spores of the diarrheal food poisoning strain B. cereus NVH 1230-88 was investigated during in vitro batch experiments simulating the stomach, duodenum and ileum using simulation media and competing intestinal microbiota. All spores and approx. 30% of the vegetative B. cereus cells survived the 2h incubation in gastric medium with pH 4.0. Sterile intestinal medium induced germination of spores and enabled outgrowth of vegetative cells to approx. 7 log CFU/mL. The behavior of B. cereus in the intestinal environment with competing intestinal bacteria was determined by their relative concentrations. Besides the numbers of intestinal bacteria, the nutrition and composition of the intestinal community were also very important for the growth inhibition of B. cereus.