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Scientific Reports Jul 2020Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. We assessed the effect of Bacteroides thetaiotaomicron...
Alterations to the gut microbiota can cause an amplification of the inflammatory response to intestinal pathogens. We assessed the effect of Bacteroides thetaiotaomicron and Lactobacillus johnsonii on the elimination of Candida species and whether restoration of these two anaerobic bacteria could attenuate the development of colitis in mice. In this study, L. johnsonii and B. thetaiotaomicron interacted directly with Candida species and induced a degradation of the fungal cell wall, mediated via chitinase-like and mannosidase-like activities, which promoted the inhibition of Candida species growth. In the DSS-induced colitis model, oral administration of L. johnsonii and B. thetaiotaomicron to mice reduced the overgrowth of Escherichia coli, Enterococcus faecalis and Candida glabrata populations and resulted in a significant reduction in inflammatory parameters. L. johnsonii and B. thetaiotaomicron decreased pro-inflammatory mediators and enhanced the anti-inflammatory cytokine response with high TLR9 expression and chitinase-like protein-1 activation, which promoted the elimination of C. glabrata from the gut. Overall, these findings provide evidence that L. johnsonii and B. thetaiotaomicron decrease the development of colitis mediated by TLR9 and promote the elimination of C. glabrata from the gut via chitinase-like and mannosidase-like activities.
Topics: Animals; Bacteroides thetaiotaomicron; Candida glabrata; Cell Wall; Gastrointestinal Microbiome; Hydrolysis; Inflammation; Inflammation Mediators; Lactobacillus johnsonii; Mice
PubMed: 32661259
DOI: 10.1038/s41598-020-68214-9 -
Research Square Jan 2023Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known...
Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing reduced severity of GVHD and improved survival. reduced degradation of colonic mucus by another intestinal commensal, , via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by and reduce GVHD-related mortality.
PubMed: 36778495
DOI: 10.21203/rs.3.rs-2460097/v1 -
Microbiology Spectrum Jun 2022Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the...
Trophic interactions between microbes are postulated to determine whether a host microbiome is healthy or causes predisposition to disease. Two abundant taxa, the Gram-negative heterotrophic bacterium Bacteroides thetaiotaomicron and the methanogenic archaeon Methanobrevibacter smithii, are proposed to have a synergistic metabolic relationship. Both organisms play vital roles in human gut health; B. thetaiotaomicron assists the host by fermenting dietary polysaccharides, whereas M. smithii consumes end-stage fermentation products and is hypothesized to relieve feedback inhibition of upstream microbes such as B. thetaiotaomicron. To study their metabolic interactions, we defined and optimized a coculture system and used software testing techniques to analyze growth under a range of conditions representing the nutrient environment of the host. We verify that B. thetaiotaomicron fermentation products are sufficient for M. smithii growth and that accumulation of fermentation products alters secretion of metabolites by B. thetaiotaomicron to benefit M. smithii. Studies suggest that B. thetaiotaomicron metabolic efficiency is greater in the absence of fermentation products or in the presence of M. smithii. Under certain conditions, B. thetaiotaomicron and M. smithii form interspecies granules consistent with behavior observed for syntrophic partnerships between microbes in soil or sediment enrichments and anaerobic digesters. Furthermore, when vitamin B, hematin, and hydrogen gas are abundant, coculture growth is greater than the sum of growth observed for monocultures, suggesting that both organisms benefit from a synergistic mutual metabolic relationship. The human gut functions through a complex system of interactions between the host human tissue and the microbes which inhabit it. These diverse interactions are difficult to model or examine under controlled laboratory conditions. We studied the interactions between two dominant human gut microbes, B. thetaiotaomicron and M. smithii, using a seven-component culturing approach that allows the systematic examination of the metabolic complexity of this binary microbial system. By combining high-throughput methods with machine learning techniques, we were able to investigate the interactions between two dominant genera of the gut microbiome in a wide variety of environmental conditions. Our approach can be broadly applied to studying microbial interactions and may be extended to evaluate and curate computational metabolic models. The software tools developed for this study are available as user-friendly tutorials in the Department of Energy KBase.
Topics: Bacteroides; Fermentation; Gastrointestinal Microbiome; Humans; Methanobrevibacter; Microbial Interactions
PubMed: 35536023
DOI: 10.1128/spectrum.01067-22 -
Gut Microbes Nov 2020As the importance of gut-brain interactions increases, understanding how specific gut microbes interact with the enteric nervous system (ENS), which is the first point...
BACKGROUND AND AIMS
As the importance of gut-brain interactions increases, understanding how specific gut microbes interact with the enteric nervous system (ENS), which is the first point of neuronal exposure becomes critical. Our aim was to understand how the dominant human gut bacterium (Bt) regulates anatomical and functional characteristics of the ENS.
METHODS
Neuronal cell populations, as well as enteroendocrine cells, were assessed in proximal colonic sections using fluorescent immunohistochemistry in specific pathogen-free (SPF), germ-free (GF) and Bt conventionalized-germ-free mice (Bt-CONV). RNA expression of tight junction proteins and toll-like receptors (TLR) were measured using qPCR. Colonic motility was analyzed using colonic manometry.
RESULTS
Decreased neuronal and vagal afferent innervation observed in GF mice was normalized by Bt-CONV with increased neuronal staining in mucosa and myenteric plexus. Bt-CONV also restored expression of nitric oxide synthase expressing inhibitory neurons and of choline acetyltransferase and substance P expressing excitatory motor neurons comparable to those of SPF mice. Neurite outgrowth and glial cells were upregulated by Bt-CONV. RNA expression of tight junction protein claudin 3 was downregulated while TLR2 was upregulated by Bt-CONV. The enteroendocrine cell subtypes L-cells and enterochromaffin cells were reduced in GF mice, with Bt-CONV restoring L-cell numbers. Motility as measured by colonic migrating motor complexes (CMMCs) increased in GF and Bt-CONV.
CONCLUSION
Bt, common gut bacteria, is critical in regulating enteric neuronal and enteroendocrine cell populations, and neurogenic colonic activity. This highlights the potential use of this resident gut bacteria for maintaining healthy gut function.
Topics: Animals; Bacteroides thetaiotaomicron; Claudin-3; Colon; Enteric Nervous System; Gastrointestinal Microbiome; Mice; Mice, Inbred C57BL; Neurons; Nitric Oxide Synthase; Specific Pathogen-Free Organisms; Tight Junctions; Toll-Like Receptor 2
PubMed: 32515657
DOI: 10.1080/19490976.2020.1766936 -
A biosynthetic pathway for the selective sulfonation of steroidal metabolites by human gut bacteria.Nature Microbiology Sep 2022Members of the human gut microbiome enzymatically process many bioactive molecules in the gastrointestinal tract. Most gut bacterial modifications characterized so far...
Members of the human gut microbiome enzymatically process many bioactive molecules in the gastrointestinal tract. Most gut bacterial modifications characterized so far are hydrolytic or reductive in nature. Here we report that abundant human gut bacteria from the phylum Bacteroidetes perform conjugative modifications by selectively sulfonating steroidal metabolites. While sulfonation is a ubiquitous biochemical modification, this activity has not yet been characterized in gut microbes. Using genetic and biochemical approaches, we identify a widespread biosynthetic gene cluster that encodes both a sulfotransferase (BtSULT, BT0416) and enzymes that synthesize the sulfonate donor adenosine 3'-phosphate-5'-phosphosulfate (PAPS), including an APS kinase (CysC, BT0413) and an ATP sulfurylase (CysD and CysN, BT0414-BT0415). BtSULT selectively sulfonates steroidal metabolites with a flat A/B ring fusion, including cholesterol. Germ-free mice monocolonized with Bacteroides thetaiotaomicron ΔBT0416 exhibited reduced gastrointestinal levels of cholesterol sulfate (Ch-S) compared with wild-type B. thetaiotaomicron-colonized mice. The presence of BtSULT and BtSULT homologues in bacteria inhibited leucocyte migration in vitro and in vivo, and abundances of cluster genes were significantly reduced in patients with inflammatory bowel disease. Together, these data provide a mechanism by which gut bacteria sulfonate steroidal metabolites and suggest that these compounds can modulate immune cell trafficking in the host.
Topics: Animals; Bacteria; Bacteroides thetaiotaomicron; Biosynthetic Pathways; Gastrointestinal Tract; Humans; Mice; Sulfate Adenylyltransferase
PubMed: 35982310
DOI: 10.1038/s41564-022-01176-y -
Microorganisms Aug 2022Bisphenols are used in the process of polymerization of polycarbonate plastics and epoxy resins. Bisphenols can easily migrate out of plastic products and enter the...
Bisphenols are used in the process of polymerization of polycarbonate plastics and epoxy resins. Bisphenols can easily migrate out of plastic products and enter the gastrointestinal system. By increasing colonic inflammation in mice, disrupting the intestinal bacterial community structure and altering the microbial membrane transport system in zebrafish, bisphenols seem to interfere with the gut microbiome. The highly abundant human commensal bacterium was exposed to bisphenols (Bisphenol A (BPA), Bisphenol F (BPF), Bisphenol S (BPS)), to examine the mode of action, in particular of BPF. All chemicals caused a concentration-dependent growth inhibition and the half-maximal effective concentration (EC50) corresponded to their individual logP values, a measure of their hydrophobicity. exposed to BPF decreased membrane fluidity with increasing BPF concentrations. Physiological changes including an increase of acetate concentrations were observed. On the proteome level, a higher abundance of several ATP synthase subunits and multidrug efflux pumps suggested an increased energy demand for adaptive mechanisms after BPF exposure. Defense mechanisms were also implicated by a pathway analysis that identified a higher abundance of members of resistance pathways/strategies to cope with xenobiotics (i.e., antibiotics). Here, we present further insights into the mode of action of bisphenols in a human commensal gut bacterium regarding growth inhibition, and the physiological and functional state of the cell. These results, combined with microbiota-directed effects, could lead to a better understanding of host health disturbances and disease development based on xenobiotic uptake.
PubMed: 36014027
DOI: 10.3390/microorganisms10081610 -
Microbiology Spectrum Feb 2022Members of the gut-dwelling genus have remarkable abilities in degrading a diverse set of fiber polysaccharide structures, most of which are found in the mammalian...
Members of the gut-dwelling genus have remarkable abilities in degrading a diverse set of fiber polysaccharide structures, most of which are found in the mammalian diet. As part of their metabolism, they convert these fibers to organic acids that can in turn provide energy to their host. While many studies have identified and characterized the genes and corresponding proteins involved in polysaccharide degradation, relatively little is known about genes involved in downstream metabolic pathways. Bacteroides thetaiotaomicron is one of the most studied species from the genus and is representative of this group in producing multiple organic acids as part of its metabolism. We focused here on several organic acid synthesis pathways in B. thetaiotaomicron, including those involved in formate, lactate, propionate, and acetate production. We identified potential genes involved in each pathway and characterized these through gene deletions coupled to growth assays and organic acid quantification. In addition, we developed and employed a Golden Gate-compatible plasmid system to simplify alteration of native gene expression levels. Our work both validates and contradicts previous bioinformatic gene annotations, and we develop a model on which to base future efforts. A clearer understanding of metabolic pathways can inform and facilitate efforts to employ these bacteria for improved human health or other utilization strategies. Both humans and animals host a large community of bacteria and other microorganisms in their gastrointestinal tracts. This community breaks down dietary fiber and produces organic acids that are used as an energy source by the body and can also help the host resist infection by various pathogens. While the Bacteroides genus is one of the most common in the gut microbiota, it is only distantly related to bacteria with well-characterized metabolic pathways and it is therefore unclear whether research insights on organic acid production in those species can also be directly applied to the Bacteroides. By investigating multiple genetic pathways for organic acid production in Bacteroides thetaiotaomicron, we provide a basis for deeper understanding of these pathways. The work further enables greater understanding of Bacteroides-host relationships, as well as inter-species relationships in the microbiota, which are of importance for both human and animal gut health.
Topics: Animals; Bacteria; Bacterial Proteins; Bacteroides thetaiotaomicron; Biosynthetic Pathways; Fatty Acids, Volatile; Gastrointestinal Microbiome; Gastrointestinal Tract; Gene Expression Regulation, Bacterial; Humans
PubMed: 35196806
DOI: 10.1128/spectrum.02312-21 -
Microbiology (Reading, England) Jul 2020Unique morphologies can enable bacteria to survive in their native environment. Furthermore, many bacteria change their cell shape to adapt to different environmental...
Unique morphologies can enable bacteria to survive in their native environment. Furthermore, many bacteria change their cell shape to adapt to different environmental conditions. For instance, some bacteria increase their surface area under carbon or nitrogen starvation. is an abundant human gut species; it efficiently degrades a number of carbohydrates and also supports the growth of other bacteria by breaking down complex polysaccharides. The gut provides a variable environment as nutrient availability is subject to the diet and health of the host, yet how gut bacteria adapt and change their morphologies under different nutrient conditions has not been studied. Here, for the first time, we report an elongated morphology under sugar-limited conditions using live-cell imaging; this elongated morphology is enhanced in the presence of sodium bicarbonate. Similarly, we also observed that sodium bicarbonate produces an elongated-length phenotype in another Gram-negative gut bacterium, . The increase in cell length might provide an adaptive advantage for cells to survive under nutrient-limited conditions.
Topics: Bacteroides thetaiotaomicron; Escherichia coli; Gastrointestinal Tract; Humans; Morphogenesis; Phenotype; Sodium Bicarbonate; Stress, Physiological; Sugars
PubMed: 32416743
DOI: 10.1099/mic.0.000924 -
Journal of Clinical Laboratory Analysis May 2022Certain "star intestinal bacteria" have been found to act as a contributor to the development of colorectal cancer (CRC). Besides, given that the gut microbiome can be... (Review)
Review
BACKGROUND
Certain "star intestinal bacteria" have been found to act as a contributor to the development of colorectal cancer (CRC). Besides, given that the gut microbiome can be detected in a diverse range of samples (stool, tissue, blood, etc), it is categorized into fecal microbiome, blood microbiome, and tissue microbiome.
METHODS
To provide an overview of the recent research progress, this review summarizes the characteristics of the gut microbiome in different samples at each stage of CRC and their screening efficiency.
RESULTS
The screening models constructed from different sample microbiomes (healthy/colorectal adenoma, healthy/CRC, and colorectal adenoma/CRC) have both strengths and constraints in terms of biomarker reproducibility and area under the receiver-operating characteristic curve (AUC) of the screening models. Many bacteria, such as Bifidobacteria, Fusobacterium nucleatum (F. n), Geotrichum candidum, Porphyromonas asaccharolytica, Escherichia coli, Rhodococcus, Anaerostipes caccae, Enhydrobacter, Lachnoclostridiumsp. m3, Bacteroides clarus, Clostridium hathewayi, Ruminococcaceae, Bacteroides thetaiotaomicron, Culinariside, and enterotoxigenic Bacteroides fragilis (ETBF), show favorable diagnostic efficacy in early screening of colorectal cancer.
CONCLUSIONS
This review highlights stool, blood, tissue, and bowel fluid are the main sample sources for biomarkers, each with its own advantages and limitations. Moreover, other samples such as extracellular vesicles and biofilms also should been deserved further attention.
Topics: Adenoma; Biomarkers; Colorectal Neoplasms; Early Detection of Cancer; Feces; Gastrointestinal Microbiome; Humans; Reproducibility of Results
PubMed: 35312122
DOI: 10.1002/jcla.24359 -
Proceedings of the National Academy of... Sep 2003Our intestine is the site of an extraordinarily complex and dynamic environmentally transmitted consortial symbiosis. The molecular foundations of beneficial symbiotic...
Our intestine is the site of an extraordinarily complex and dynamic environmentally transmitted consortial symbiosis. The molecular foundations of beneficial symbiotic host-bacterial relationships in the gut are being revealed in part from studies of simplified models of this ecosystem, where germ-free mice are colonized with specified members of the microbial community, and in part from comparisons of the genomes of members of the intestinal microbiota. The results emphasize the contributions of symbionts to postnatal gut development and host physiology, as well as the remarkable strategies these microorganisms have evolved to sustain their alliances. These points are illustrated by the human-Bacteroides thetaiotaomicron symbiosis. Interdisciplinary studies of the effects of the intestinal environment on genome structure and function should provide important new insights about how microbes and humans have coevolved mutually beneficial relationships and new perspectives about the foundations of our health.
Topics: Animals; Bacteroides; Biological Evolution; Ecosystem; Genome, Bacterial; Genomics; Germ-Free Life; Humans; Intestines; Polysaccharides, Bacterial; Symbiosis
PubMed: 12923294
DOI: 10.1073/pnas.1734063100