scholarly journals Microbial Colonization in Adulthood Shapes the Intestinal Macrophage Compartment

2019 ◽  
Vol 13 (9) ◽  
pp. 1173-1185 ◽  
Author(s):  
Franziska Schmidt ◽  
Katja Dahlke ◽  
Arvind Batra ◽  
Jacqueline Keye ◽  
Hao Wu ◽  
...  

Abstract Background and Aims Contact with distinct microbiota early in life has been shown to educate the mucosal immune system, hence providing protection against immune-mediated diseases. However, the impact of early versus late colonization with regard to the development of the intestinal macrophage compartment has not been studied so far. Methods Germ-free mice were colonized with specific-pathogen-free [SPF] microbiota at the age of 5 weeks. The ileal and colonic macrophage compartment were analysed by immunohistochemistry, flow cytometry, and RNA sequencing 1 and 5 weeks after colonization and in age-matched SPF mice, which had had contact with microbiota since birth. To evaluate the functional differences, dextran sulfate sodium [DSS]-induced colitis was induced, and barrier function analyses were undertaken. Results Germ-free mice were characterized by an atrophied intestinal wall and a profoundly reduced number of ileal macrophages. Strikingly, morphological restoration of the intestine occurred within the first week after colonization. In contrast, ileal macrophages required 5 weeks for complete restoration, whereas colonic macrophages were numerically unaffected. However, following DSS exposure, the presence of microbiota was a prerequisite for colonic macrophage infiltration. One week after colonization, mild colonic inflammation was observed, paralleled by a reduced inflammatory response after DSS treatment, in comparison with SPF mice. This attenuated inflammation was paralleled by a lack of TNFα production of LPS-stimulated colonic macrophages from SPF and colonized mice, suggesting desensitization of colonized mice by the colonization itself. Conclusions This study provides the first data indicating that after colonization of adult mice, the numeric, phenotypic, and functional restoration of the macrophage compartment requires the presence of intestinal microbiota and is time dependent.

2016 ◽  
Vol 113 (47) ◽  
pp. E7554-E7563 ◽  
Author(s):  
Jing Yan ◽  
Jeremy W. Herzog ◽  
Kelly Tsang ◽  
Caitlin A. Brennan ◽  
Maureen A. Bower ◽  
...  

Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.


2018 ◽  
Author(s):  
Carola I. Radulescu ◽  
Marta Garcia-Miralles ◽  
Harwin Sidik ◽  
Costanza Ferrari Bardile ◽  
Nur Amirah Binte Mohammad Yusof ◽  
...  

ABSTRACTStructural and molecular myelination deficits represent early pathological features of Huntington disease (HD). Recent evidence from germ-free (GF) animals suggests a role for microbiota-gut-brain bidirectional communication in the regulation of myelination. In this study, we aimed to investigate the impact of microbiota on myelin plasticity and oligodendroglial population dynamics in the mixed-sex BACHD mouse model of HD. Ultrastructural analysis of myelin in the corpus callosum revealed alterations of myelin thickness in BACHD GF compared to specific-pathogen free (SPF) mice, whereas no differences were observed between wild-type (WT) groups. In contrast, myelin compaction was altered in all groups when compared to WT SPF animals. Levels of myelin-related proteins were generally reduced, and the number of mature oligodendrocytes was decreased in the prefrontal cortex under GF compared to SPF conditions, regardless of genotype. Minor differences in commensal bacteria at the family and genera levels were found in the gut microbiota of BACHD and WT animals housed in standard living conditions. Our findings indicate complex effects of a germ-free status on myelin-related characteristics, and highlight the adaptive properties of myelination as a result of environmental manipulation.


mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Darin Quach ◽  
Fraser Collins ◽  
Narayanan Parameswaran ◽  
Laura McCabe ◽  
Robert A. Britton

ABSTRACTAnnually, an estimated 2 million osteoporotic fractures occur in the United States alone. Osteoporosis imparts a great burden on the health care system. The identification of novel regulators of bone health is critical for developing more effective therapeutics. A previous study on the colonization of germ-free (GF) mice with a microbial community has demonstrated that bacterial colonization dramatically increases bone loss. We therefore investigated the impact of multiple microbial communities in different mice to understand how generalizable the impact of bacterial colonization is on bone health. To investigate the impact of different microbial communities on bone health in outbred and inbred mouse strains, gavage was performed on GF Swiss Webster and GF C57BL/6 mice to introduce distinct microbiotas that originated from either humans or mice. GF mice displayed a high degree of colonization, as indicated by more than 90% of the operational taxonomic units present in the starting inoculum being successfully colonized in the mice when they were examined at the end of the experiment. In spite of the successful colonization of GF mice with gut microbiota of either mouse or human origin, bone mass did not change significantly in any of the groups tested. Furthermore, static and dynamic bone parameters and osteoclast precursor and T cell populations, as well as the expression of several inflammatory markers, were mostly unchanged following microbial colonization of GF mice.IMPORTANCEThe microbiota has been shown to be an important regulator of health and development. With regard to its effect on bone health, a previous study has suggested that gut microbes negatively impact bone density. However, we show here that this is not generalizable to all microbial communities and mouse strain backgrounds. Our results demonstrate that colonization of mice, both outbred and inbred strains, did not have a major impact on bone health. The identification of microbial communities that do not negatively impact bone health may provide a foundation for future investigations that seek to identify microbes that are either beneficial or detrimental to bone metabolism.


Author(s):  
Paulina Kowalczyk ◽  
Anna Strzępa ◽  
Marian Szczepanik

Abstract Background Antibiotics, while eliminating pathogens, also partially deplete commensal bacteria. Antibiotic-induced dysbiosis may contribute to the observed rise in “immune-mediated” diseases, including autoimmunity and allergy. The aim of this study is to investigate the impact of perinatal antibiotic treatment on T cell-mediated immune response in adult mice. Methods Oral treatment with broad-spectrum antibiotic enrofloxacin during gestation and breastfeeding or breastfeeding or gestation alone was used to evaluate whether antibiotic exposure early in life could modulate contact sensitivity (CS) in adult mice. Results Here, we demonstrated that enrofloxacin treatment during gestation and breastfeeding, but not during pregnancy or breastfeeding alone, aggravated CS reaction in adult mice measured by ear swelling. These data correlate with increased myeloperoxidase (MPO) activity in the ear extracts and elevated production of IL-6 and IL-17A by auricular lymph node cells (ELNC) and was not influenced by food consumption and body weight. In each dosing regimen, enrofloxacin treatment reduced the relative abundance of Enterococcus spp. but did not influence the relative abundances of Lactobacillus, Clostridium cluster XIVa, XIVab, I, Bacteroidetes, and segmented filamentous bacteria (SFB). However, prolonged enrofloxacin-treatment during both gestation and breastfeeding decreased the relative abundance of Clostridium cluster IV. Conclusion These data show that long-term perinatal enrofloxacin treatment induces intestinal dysbiosis, characterized by decreased levels of anti-inflammatory Clostridium cluster IV, and alters T cell-dependent immune responses, enhancing CS reaction in adult mice.


2020 ◽  
Vol 91 (8) ◽  
pp. 651-661
Author(s):  
Joshua T. Davis ◽  
Hilary A. Uyhelji

INTRODUCTION: Although the impact of microorganisms on their hosts has been investigated for decades, recent technological advances have permitted high-throughput studies of the collective microbial genomes colonizing a host or habitat, also known as the microbiome. This literature review presents an overview of microbiome research, with an emphasis on topics that have the potential for future applications to aviation safety. In humans, research is beginning to suggest relationships of the microbiome with physical disorders, including type 1 and type 2 diabetes mellitus, cardiovascular disease, and respiratory disease. The microbiome also has been associated with psychological health, including depression, anxiety, and the social complications that arise in autism spectrum disorders. Pharmaceuticals can alter microbiome diversity, and may lead to unintended consequences both short and long-term. As research strengthens understanding of the connections between the microbiota and human health, several potential applications for aerospace medicine and aviation safety emerge. For example, information derived from tests of the microbiota has potential future relevance for medical certification of pilots, accident investigation, and evaluation of fitness for duty in aerospace operations. Moreover, air travel may impact the microbiome of passengers and crew, including potential impacts on the spread of disease nationally and internationally. Construction, maintenance, and cleaning regimens that consider the potential for microbial colonization in airports and cabin environments may promote the health of travelers. Altogether, the mounting knowledge of microbiome effects on health presents several opportunities for future research into how and whether microbiome-based insights could be used to improve aviation safety.Davis JT, Uyhelji HA. Aviation and the microbiome. Aerosp Med Hum Perform. 2020; 91(8):651–661.


Author(s):  
E.N. Glavatskaya , O.V. Pribushenya , N.A. Venchikova

Two clinical cases of meconium peritonitis in the fetuses are presented. The diagnosis was made prenatally at 30+5 and 20+1 weeks of gestation. The main ultrasound signs were ascites, loop expansion and thickening of the intestinal wall, peritoneal calcifications, meconium pseudocysts. In one case, pregnancy was complicated by polyhydramnios. In both cases, the pregnancy ended in premature birth, followed by surgical treatment during the first days of life. A review of the literature on the topic are discussed the etiology, the spectrum and frequency of ultrasound signs suggesting this condition in the fetus, the effectiveness of prenatal diagnosis, the prognosis for the life and health of the newborn, as well as the impact of the quality and timeliness of the prenatal diagnosis on the management of pregnancy and timeliness of surgical care for the newborn.


2019 ◽  
Vol 97 (9) ◽  
pp. 3741-3757 ◽  
Author(s):  
Nirosh D Aluthge ◽  
Dana M Van Sambeek ◽  
Erin E Carney-Hinkle ◽  
Yanshuo S Li ◽  
Samodha C Fernando ◽  
...  

Abstract A variety of microorganisms inhabit the gastrointestinal tract of animals including bacteria, archaea, fungi, protozoa, and viruses. Pioneers in gut microbiology have stressed the critical importance of diet:microbe interactions and how these interactions may contribute to health status. As scientists have overcome the limitations of culture-based microbiology, the importance of these interactions has become more clear even to the extent that the gut microbiota has emerged as an important immunologic and metabolic organ. Recent advances in metagenomics and metabolomics have helped scientists to demonstrate that interactions among the diet, the gut microbiota, and the host to have profound effects on animal health and disease. However, although scientists have now accumulated a great deal of data with respect to what organisms comprise the gastrointestinal landscape, there is a need to look more closely at causative effects of the microbiome. The objective of this review is intended to provide: 1) a review of what is currently known with respect to the dynamics of microbial colonization of the porcine gastrointestinal tract; 2) a review of the impact of nutrient:microbe effects on growth and health; 3) examples of the therapeutic potential of prebiotics, probiotics, and synbiotics; and 4) a discussion about what the future holds with respect to microbiome research opportunities and challenges. Taken together, by considering what is currently known in the four aforementioned areas, our overarching goal is to set the stage for narrowing the path towards discovering how the porcine gut microbiota (individually and collectively) may affect specific host phenotypes.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.


Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 584
Author(s):  
Natalia Nunez ◽  
Louis Réot ◽  
Elisabeth Menu

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.


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