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Search for other papers by Muhammad Hassan Saeed in
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Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK
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The early-life microbiota is an ‘immature’ and highly dynamic microbial ecosystem, which is central to infant health. Both perinatal and postnatal factors can impact the gut microbiota, with antibiotics proposed to cause short and longer-term disturbances. Antibiotics not only impact microbial community composition but also contribute to the overall antibiotic resistance profile, i.e. the ‘resistome’, and they may also enhance carriage of multi-drug-resistant bacteria. Given high antibiotic prescription practices in pregnant women and newborns this also contributes to the global threat of antimicrobial resistance. This review summarises the current literature on antibiotic usage and how this may impact the developing gut microbiota during early-life, including the influence of horizontal gene transfer on contributions to pathogenicity and resistance of gut bacteria. We also focus on Enterococcus spp. given their high levels in infants and their link with opportunistic infections that are a significant cause of morbidity and mortality during early-life. Finally, a perspective on the importance to antibiotic stewardship, and harnessing the microbiota itself for anti-infection therapies for reducing antibiotic usage are also covered.
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Many, if not all, plants and animals form mutually beneficial symbioses (mutualisms) with microbes and a subset of these mutualisms are defensive, in which the host provides food and housing in return for defence against disease. These symbioses typically involve antibiotic-producing bacteria, the best known of which are filamentous actinomycetes in the genera Streptomyces and Pseudonocardia and unicellular species in the genus Pseudomonas. Such mutualisms are likely to be widespread in nature, but they are best characterised in insects, which provide experimentally tractable models for studying symbiosis and microbiome formation because they typically host less complex microbial communities. Here, we examine the mutualisms formed between insects and antibiotic-producing bacteria using well-characterised examples, including digger wasps and their endosymbiotic Streptomyces species, attine ants and their mutualist Pseudonocardia species and Paederus beetles with their pederin-producing Pseudomonas species. We also discuss how searching such symbiotic niches can give insights into the evolution and functions of microbial specialised metabolites and provide new platforms for antibiotic discovery.
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Search for other papers by John Henry Dasinger in
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Search for other papers by Bina Joe in
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Search for other papers by Justine M Abais-Battad in
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Consistent research over the last 20 years has shown that there are clear sex differences in the pathogenesis of hypertension, the leading risk factor for the development of cardiovascular diseases. More recently, there is evidence in both humans and experimental animal models that causally implicates the gut microbiota in hypertension. It therefore follows that sex differences in the gut microbiota may mediate the extent of disease between sexes. This new field is rapidly changing and advancing, and the purpose of this review is to cover the most up-to-date evidence regarding the sexual dimorphism of the gut microbiota and its potential influence on the differential manifestation of hypertension in males versus females. Emphasis will be placed on the mechanisms thought to contribute to these sex differences in both the gut microbiota and hypertension, including sex steroid hormones, gut-derived metabolites, the immune system, and pregnancy.
The Gut Microbiome Center (CCM), Zagreb, Croatia
Search for other papers by Andrija Karačić in
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Search for other papers by Jasna Novak in
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School of Medicine, University of Zagreb, Zagreb, Croatia
Department of Clinical Medicine, University of Applied Health Sciences, Zagreb, Croatia
Search for other papers by Alan Ivković in
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The recent recognition of the importance of the intestinal microbiome in host physiology has driven investigations of gut microbiome-directed therapeutics, with probiotics attracting increased attention in the treatment of a diversity of conditions. The application of probiotics has expanded beyond the treatment of intestinal tract disorders. Today, their capacity to treat a vast array of conditions arising also along the gut–bone axis is being studied. Therefore, in this study we have carried out a scoping literature review of the clinical trials evaluating the effect of probiotics in the treatment of bone fracture. In total, six articles were found for review, four randomized placebo-controlled trials on humans and two studies using animal models. Probiotics were found to have positive effects on fracture treatment. Probiotics were shown to improve not only bone regeneration but also decrease systemic inflammation and pain during conservative fracture treatment. However, this is a novel field and due to the limited number of studies only sparse conclusions can be made. Additional clinical trials on the possible role of probiotics in fracture treatment are necessary to fully evaluate their therapeutic potential.
Search for other papers by John C Alverdy in
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Despite major advances in infection control and the ever-increasing use of broader-spectrum antibiotics in surgery, postoperative infections continue to occur under the best of care and in the best institutions. Postoperative infections, also termed surgical site infections (SSIs), can range from superficial wound infections to deep organ space infections. SSIs can be superficial and only require medical treatment (i.e. antibiotics), whereas others such as deep organ space infections resulting from an anastomotic leak can require multiple surgeries leading to sepsis and occasionally shock and death. Many if not most stakeholders in the field including surgeons, infectious disease specialists, infection control nurses, etc., in general, advocate the use of prophylactic antibiotics and the enforcement of greater levels of sterility, reasoning that all postoperative infections must arise from some type of direct contamination event. In this article, the alternative view is presented that today, in the era of mandated asepsis protocols, enhanced recovery programs, and enforcement of prophylactic antibiotics in all cases, many if not most postoperative infections and SSIs occur from pathogens endogenous to the patient and not from sources exogenous to the patient. It is also suggested that applying broader antibiotic coverage in elective surgery is neither an evolutionarily stable strategy nor inexorable in the context of emerging knowledge in the field of gut ecology. Here this concept is reviewed and the rationale behind using agents that preserve the gut microbiome and attenuate pathogen virulence in lieu of applying broader-spectrum antibiotics and greater levels of sterility.
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Microbiota composition is known to be linked to sex. However, separating sex hormones and sex chromosome roles in gut microbial diversity is yet to be determined. To investigate the sex chromosome role independent of sex hormones, we used the four-core genotype mouse model. In this mouse model, males with testes and females with ovaries have XX or XY sex chromosome complement. In gonadectomized four-core genotype mice, we observed a significant decrease in the levels of estradiol (P < 0.001) and progesterone (P < 0.03) in female and testosterone (P < 0.0001) in male mice plasma samples. Independent of sex chromosome complement, microbial α diversity was increased in gonadectomized female but not male mice compared to sex-matched gonad-intact controls. β diversity analysis showed separation between male (P < 0.05) but not female XX and XY mice. Importantly, Akkermansiamuciniphila was less abundant in gonadectomized compared to gonadal intact female mice (P < 0.0001). In the presence of β-estradiol, A.muciniphila growth exponentially increased, providing evidence for the identification of a female sex hormone-responsive bacterium (P < 0.001).
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Search for other papers by Sarah E Blutt in
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The epithelial lining of the small intestine mediates its absorptive and secretory function and thus is a critical component of human health. Regeneration and renewal of the epithelium is the result of proliferation of intestinal stem cells (ISCs). Many cell types and molecular factors are known to regulate the ability of ISCs to proliferate, including adjacent neighboring epithelial cells and the underlying, supportive stromal cells. The microbiome resides in the lumen of the small intestine and is in close contact with the epithelium. Due to its proximity to ISCs, it has been hypothesized that species within the microbiome have the capacity to regulate ISC proliferation and differentiation. This review highlights research that probes interactions between ISCs and the microbiome in the small intestine to detail the current understanding of microbial regulation of ISCs. Results from these studies provide important knowledge that can be exploited to identify therapeutic targets or develop novel preventative treatments to treat intestinal diseases.
