Pathogenesis of Children's Allergic Diseases: Refocusing the Role of the Gut Microbiota.

Allergic diseases comprise a genetically heterogeneous cluster of immunologically mediated diseases, including asthma, food allergy (FA), allergic rhinitis (AR) and eczema, that have become major worldwide health problems. Over the past few decades, the spread of allergic diseases has displayed an increasing trend, and it has been reported that 22% of 1.39 billion people in 30 countries have a type of allergic disease. Undoubtedly, allergic diseases, which can be chronic, with significant morbidity, mortality and dynamic progression, impose major economic burdens on society and families; thus, exploring the cause of allergic diseases and reducing their prevalence is a top priority. Recently, it has been reported that the gastrointestinal (GI) microbiota can provide vital signals for the development, function, and regulation of the immune system, and the above-mentioned contributions make the GI microbiota a key player in allergic diseases. Notably, the GI microbiota is highly influenced by the mode of delivery, infant diet, environment, antibiotic use and so on. Specifically, changes in the environment can result in the dysbiosis of the GI microbiota. The proper function of the GI microbiota depends on a stable cellular composition which in the case of the human microbiota consists mainly of bacteria. Large shifts in the ratio between these phyla or the expansion of new bacterial groups lead to a disease-promoting imbalance, which is often referred to as dysbiosis. And the dysbiosis can lead to alterations of the composition of the microbiota and subsequent changes in metabolism. Further, the GI microbiota can affect the physiological characteristics of the human host and modulate the immune response of the host. The objectives of this review are to evaluate the development of the GI microbiota, the main drivers of the colonization of the GI tract, and the potential role of the GI microbiota in allergic diseases and provide a theoretical basis as well as molecular strategies for clinical practice.

A Minireview on Gastrointestinal Microbiota and Radiosusceptibility.

Gastrointestinal (GI) microbiota maintains a symbiotic relationship with the host and plays a key role in modulating many important biological processes and functions of the host, such as metabolism, inflammation, immune and stress response. It is becoming increasingly apparent that GI microbiota is susceptible to a wide range of environmental factors and insults, for examples, geographic location of birth, diet, use of antibiotics, and exposure to radiation. Alterations in GI microbiota link to various diseases, including radiation-induced disorders. In addition, GI microbiota composition could be used as a biomarker to estimate radiosusceptibility and radiation health risk in the host. In this minireview, we summarized the documented studies on radiation-induced alterations in GI microbiota and the relationship between GI microbiota and radiosusceptibility of the host, and mainly discussed the possible mechanisms underlying GI microbiota influencing the outcome of radiation response in humans and animal models. Furthermore, we proposed that GI microbiota manipulation may be used to reduce radiation injury and improve the health of the host.

Gut microbial ß-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens.

Gut microbial ß-glucuronidase (GUS) enzymes have been suggested to be involved in the estrobolome, the collection of microbial reactions involving estrogens. Furthermore, bacterial GUS enzymes within the gastrointestinal tract have been postulated to be a contributing factor in hormone-driven cancers. However, to date, there has been no experimental evidence to support these hypotheses. Here we provide the first in vitro analysis of the ability of 35 human gut microbial GUS enzymes to reactivate two distinct estrogen glucuronides, estrone-3-glucuronide and estradiol-17-glucuronide, to estrone and estradiol, respectively. We show that certain members within the Loop 1, mini-Loop 1, and FMN-binding classes of gut microbial GUS enzymes can reactivate estrogens from their inactive glucuronides. We provide molecular details of key interactions that facilitate these catalytic processes and present the structures of two novel human gut microbial GUS enzymes related to the estrobolome. Further, we demonstrate that estrogen reactivation by Loop 1 bacterial GUS enzymes can be inhibited both in purified enzymes and in fecal preparations of mixed murine fecal microbiota. Finally, however, despite these in vitro and ex vivo data, we show that a Loop 1 GUS-specific inhibitor is not capable of reducing the development of tumors in the PyMT mouse model of breast cancer. These findings validate that gut microbial GUS enzymes participate in the estrobolome but also suggest that the estrobolome is a multidimensional set of processes on-going within the mammalian gastrointestinal tract that likely involves many enzymes, including several distinct types of GUS proteins.

Multilevel social structure and diet shape the gut microbiota of the gelada monkey, the only grazing primate.

BACKGROUND: The gelada monkey (Theropithecus gelada), endemic to the Ethiopian highlands, is the only graminivorous primate, i.e., it feeds mainly on grasses and sedges. In spite of known dental, manual, and locomotor adaptations, the intestinal anatomy of geladas is similar to that of other primates. We currently lack a clear understanding of the adaptations in digestive physiology necessary for this species to subsist on a graminoid-based diet, but digestion in other graminivores, such as ruminants, relies heavily on the microbial community residing in the gastrointestinal (GI) system. Furthermore, geladas form complex, multilevel societies, making them a suitable system for investigating links between sociality and the GI microbiota. RESULTS: Here, we explore the gastrointestinal microbiota of gelada monkeys inhabiting an intact ecosystem and document how factors like multilevel social structure and seasonal changes in diet shape the GI microbiota. We compare the gelada GI microbiota to those of other primate species, reporting a gradient from geladas to herbivorous specialist monkeys to dietary generalist monkeys and lastly humans, the ultimate ecological generalists. We also compare the microbiotas of the gelada GI tract and the sheep rumen, finding that geladas are highly enriched for cellulolytic bacteria associated with ruminant digestion, relative to other primates. CONCLUSIONS: This study represents the first analysis of the gelada GI microbiota, providing insights into the adaptations underlying graminivory in a primate. Our results also highlight the role of social organization in structuring the GI microbiota within a society of wild animals.

Microbial Molecules from the Multitudes within Us.

Chemists demonstrate in Cell that intestinal microbes are capable of synthesizing metabolites that look like clinical drugs and inhibit human targets. These results provide molecular resolution to the field of mammalian-microbial mutualism and highlight the potential for natural product discovery from the multitudes within us.