An RNA regulates iron homeostasis and host mucus colonization inBacteroides thetaiotaomicron

Meta'omic Analytic Techniques for Studying the Intestinal Microbiome

Conservation and the microbiome.

The Human Gut Microbiome: The Ghost in the Machine

SARS-CoV-2, one of the human RNA viruses, is widely studied around the world. Significant efforts have been made to understand its molecular mechanisms of action and how it interacts with epithelial cells and the human microbiome since it has also been observed in gut microbiome bacteria. Many studies emphasize the importance of surface immunity and also that the mucosal system is critical in the interaction of the pathogen with the cells of the oral, nasal, pharyngeal, and intestinal epithelium. Recent studies have shown how bacteria in the human gut microbiome produce toxins capable of altering the classical mechanisms of interaction of viruses with surface cells. This paper presents a simple approach to highlight the initial behavior of a novel pathogen, SARS-CoV-2, on the human microbiome. The immunofluorescence microscopy technique can be combined with spectral counting performed at mass spectrometry of viral peptides in bacterial cultures, along with identification of the presence of D-amino acids within viral peptides in bacterial cultures and in patients' blood. This approach makes it possible to establish the possible expression or increase of viral RNA viruses in general and SARS-CoV-2, as discussed in this study, and to determine whether or not the microbiome is involved in the pathogenetic mechanisms of the viruses. This novel combined approach can provide information more rapidly, avoiding the biases of virological diagnosis and identifying whether a virus can interact with, bind to, and infect bacteria and epithelial cells. Understanding whether some viruses have bacteriophagic behavior allows vaccine therapies to be focused either toward certain toxins produced by bacteria in the microbiome or toward finding inert or symbiotic viral mutations with the human microbiome. This new knowledge opens a scenario on a possible future vaccine: the probiotics vaccine, engineered with the right resistance to viruses that attach to both the epithelium human surface and gut microbiome bacteria.

The agents we now know as bacteria have been known for centuries to play a key role in certain kinds of illnesses and ailments. But aside from infectious diseases, the communities of microbes we carry in specific parts of our bodies—our microbiomes—are a relatively new topic in human health. Now this field of study has taken an evolutionary leap forward with new research showing human microbiomes may play a far greater role in environ-mental health than ever imagined. The excitement around this field was obvious at a National Academy of Sciences (NAS) workshop on the interplay of the microbiomes, environ-mental agents, and human health held 27–28 April 2011,1 where talks by researchers working in this area inspired numerous “eureka!” moments. New findings about the ways in which human microbiomes transform arsenic and mercury—two of our most prevalent and well-defined external human health hazards—suggest the role of commensal bacteria may equal or exceed that of genetic polymorphisms that regulate metal transformations within the body, says Ellen Silbergeld, a professor of environmental health sciences at the Johns Hopkins University Bloomberg School of Public Health. The implications of these new insights are staggering. Environmental health scientists may need to expand the toxicokinetics of metals and other environmental agents, as well as associated biomarkers, to include the microbial component. “This is a huge thing that has never been thought of before in environmental health sciences,” Silbergeld told workshop attendees. Emerging findings also demand a re-examination of what it means to be exposed to environmental agents, Silbergeld says. To a toxicologist, she explains, a contaminant is only “in the body” once it has crossed from the external environment into circulating blood, or a cell, or an organ. But new findings suggest biologically relevant transformations may take place prior to absorption, when contaminants interact with the microbiome in the mouth, intestines, or other tissues. Because of the metabolic processes mediated by microbiomes, a great deal of what toxicologists attribute to human metabolism—such as methylation of arsenic—may actually take place at least in part before contaminants cross into the internal environment of our bodies.

The gut microbiota influences the development and progression of metabolic diseases partly by metabolism of bile acids (BAs) and modified signaling through the farnesoid X receptor (FXR). In this study, we aimed to determine how the human gut microbiota metabolizes murine BAs and affects FXR signaling in colonized mice. We colonized germ-free mice with cecal content from a mouse donor or feces from a human donor and euthanized the mice after short-term (2 weeks) or long-term (15 weeks) colonization. We analyzed the gut microbiota and BA composition and expression of FXR target genes in ileum and liver. We found that cecal microbiota composition differed between mice colonized with mouse and human microbiota and was stable over time. Human and mouse microbiota reduced total BA levels similarly, but the humanized mice produced less secondary BAs. The human microbiota was able to reduce the levels of tauro-β-muricholic acid and induce expression of FXR target genes Fgf15 and Shp in ileum after long-term colonization. We show that a human microbiota can change BA composition and induce FXR signaling in colonized mice, but the levels of secondary BAs produced are lower than in mice colonized with a mouse microbiota.

The neonatal period represents a critical stage for the establishment and development of the gut microbiota, which profoundly influences the future health trajectory of individuals. This review examines the importance of intestinal microbiota in humans and dogs, aiming to elucidate the distinct characteristics and variations in the composition between these two species. In humans, the intestinal microbiota contributes to several crucial physiological processes, including digestion, nutrient absorption, immune system development, and modulation of host metabolism. Dysbiosis, an imbalance or disruption of the gut microbial community, has been linked to various disorders, such as inflammatory bowel disease, obesity, and even neurological conditions. Furthermore, recent research has unveiled the profound influence of the gut-brain axis, emphasizing the bidirectional communication between the gut microbiota and the central nervous system, impacting cognitive function and mental health. Similarly, alterations in the canine intestinal microbiota have been associated with gastrointestinal disorders, including chronic enteropathy, such as inflammatory bowel disease, food allergies, and ulcerative histiocytic colitis. However, our understanding of the intricacies and functional significance of the intestinal microbiota in dogs remains limited. Understanding the complex dynamics of the intestinal microbiota in both humans and dogs is crucial for devising effective strategies to promote health and manage disease. Moreover, exploring the similarities and differences in the gut microbial composition between these two species can facilitate translational research, potentially leading to innovative therapeutic interventions and strategies to enhance the well-being of both humans and dogs.

BackgroundCampylobacter jejuni is a major cause of inflammatory diarrhoea in humans and is considered a commensal of the gastroenteric tract of the avian host. However, little is known about the interaction between C. jejuni and the avian host including the cytokine responses and the expression of the bacterial genes. We have investigated the invasiveness of primary chicken embryo intestinal cells (CEICs) by C. jejuni strains of human and chicken origins and the production of pro-inflammatory cytokines as well as the expression of the bacterial virulence-associated genes during co-cultivation.ResultsC. jejuni strains are capable of invading the CEICs and stimulate these cells in a pro-inflammatory manner and during this interaction the expression of the bacterial virulence-associated genes ciaB, dnaJ and racR is increased. Furthermore, incubation of bacteria with conditioned cell- and bacteria-free media from another co-cultivation experiment also increased the expression of the virulence-associated genes in the C. jejuni chicken isolate, indicating that the expression of bacterial genes is regulated by component(s) secreted upon co-cultivation of bacteria and CEICs.ConclusionWe show that under in vitro culture condition C. jejuni strains of both human and chicken origins can invade avian host cells with a pro-inflammatory response and that the virulence-associated genes of C. jejuni may play a role in this process.

The Intestinal Metabolome: An Intersection Between Microbiota and Host

Gnotobiotic rats harboring human intestinal microbiota as a model for studying cholesterol-to-coprostanol conversion

Bacterial interactions with eukaryotic hosts are complex processes which vary from pathogenic to mutualistic. Identification of bacterial genes differentially expressed in the host, promises to unravel molecular mechanisms driving and maintaining such interactions. Several techniques have been developed in the past 20 years to investigate bacterial gene expression within their hosts. The most commonly used techniques include in-vivo expression technology, signature-tagged mutagenesis, differential fluorescence induction, and cDNA microarrays. However, the limitations of these techniques in analyzing bacterial in-vivo gene expression indicate the need to develop alternative tools. With many advantages over the other methods for analyzing bacterial in-vivo gene expression, selective capture of transcribed sequences (SCOTS) technique has the prospect of becoming an elegant tool for discovery of genes involved in the bacterium-host interaction. Here, we summarize the advances in SCOTS technique, including its current and potential applications in bacterial gene expression studies under a variety of conditions from in-vitro to in-vivo and from mammals to insects.

Adherence of Cervical, Vaginal and Distal Urethral Normal Microbial Flora to Human Uroepithelial Cells and the Inhibition of Adherence of Gram-Negative Uropathogens by Competitive Exclusion

BackgroundComparative data from non-human primates provide insight into the processes that shaped the evolution of the human gut microbiome and highlight microbiome traits that differentiate humans from other primates. Here, in an effort to improve our understanding of the human microbiome, we compare gut microbiome composition and functional potential in 14 populations of humans from ten nations and 18 species of wild, non-human primates.ResultsContrary to expectations from host phylogenetics, we find that human gut microbiome composition and functional potential are more similar to those of cercopithecines, a subfamily of Old World monkey, particularly baboons, than to those of African apes. Additionally, our data reveal more inter-individual variation in gut microbiome functional potential within the human species than across other primate species, suggesting that the human gut microbiome may exhibit more plasticity in response to environmental variation compared to that of other primates.ConclusionsGiven similarities of ancestral human habitats and dietary strategies to those of baboons, these findings suggest that convergent ecologies shaped the gut microbiomes of both humans and cercopithecines, perhaps through environmental exposure to microbes, diet, and/or associated physiological adaptations. Increased inter-individual variation in the human microbiome may be associated with human dietary diversity or the ability of humans to inhabit novel environments. Overall, these findings show that diet, ecology, and physiological adaptations are more important than host-microbe co-diversification in shaping the human microbiome, providing a key foundation for comparative analyses of the role of the microbiome in human biology and health.

BackgroundWithin seven days following peroral high dose infection with Toxoplasma gondii susceptible conventionally colonized mice develop acute ileitis due to an underlying T helper cell (Th) -1 type immunopathology. We here addressed whether mice harboring a human intestinal microbiota developed intestinal, extra-intestinal and systemic sequelae upon ileitis induction.Methodology/Principal findingsSecondary abiotic mice were generated by broad-spectrum antibiotic treatment and associated with a complex human intestinal microbiota following peroral fecal microbiota transplantation. Within three weeks the human microbiota had stably established in the murine intestinal tract as assessed by quantitative cultural and culture-independent (i.e. molecular 16S rRNA based) methods. At day 7 post infection (p.i.) with 50 cysts of T. gondii strain ME49 by gavage human microbiota associated (hma) mice displayed severe clinical, macroscopic and microscopic sequelae indicating acute ileitis. In diseased hma mice increased numbers of innate and adaptive immune cells within the ileal mucosa and lamina propria and elevated intestinal secretion of pro-inflammatory mediators including IFN-γ, IL-12 and nitric oxide could be observed at day 7 p.i. Ileitis development was accompanied by substantial shifts in intestinal microbiota composition of hma mice characterized by elevated total bacterial loads and increased numbers of intestinal Gram-negative commensals such as enterobacteria and Bacteroides / Prevotella species overgrowing the small and large intestinal lumen. Furthermore, viable bacteria translocated from the inflamed ileum to extra-intestinal including systemic compartments. Notably, pro-inflammatory immune responses were not restricted to the intestinal tract as indicated by increased pro-inflammatory cytokine secretion in extra-intestinal (i.e. liver and kidney) and systemic compartments including spleen and serum.Conclusion/SignificanceWith respect to the intestinal microbiota composition “humanized” mice display acute ileitis following peroral high dose T. gondii infection. Thus, hma mice constitute a suitable model to further dissect the interactions between pathogens, human microbiota and vertebrate host immunity during acute intestinal inflammation.

The human intestine hosts a vast and complex microbial community that is vital for maintaining several functions related with host health. The processes that determine the gut microbiome composition are poorly understood, being the interaction between species, the external environment, and the relationship with the host the most feasible. Animal models offer the opportunity to understand the interactions between the host and the microbiota. There are different gnotobiotic mice or rat models colonized with the human microbiota, however, to our knowledge, there are no reports on the colonization of germ-free zebrafish with a complex human intestinal microbiota. In the present study, we have successfully colonized 5 days postfertilization germ-free zebrafish larvae with the human intestinal microbiota previously extracted from a donor and analyzed by high-throughput sequencing the composition of the transferred microbial communities that established inside the zebrafish gut. Thus, we describe for first time which human bacteria phylotypes are able to colonize the zebrafish digestive tract. Species with relevant interest because of their linkage to dysbiosis in different human diseases, such as Akkermansia muciniphila, Eubacterium rectale, Faecalibacterium prausnitzii, Prevotella spp., or Roseburia spp. have been successfully transferred inside the zebrafish digestive tract.