Common Gut Microbes Research Articles

Black Soldier Fly (Hermetia illucens) Microbiome and Microbe Interactions: A Scoping Review

Black soldier fly (Hermetia illucens, BSF) is farmed worldwide to convert organic waste into usable biomaterials. Studies on the larval microbiome have been carried out to check for symbiotic or pathogenic microbes and their respective functions and fates. Some studies tested these microbes for industrial applications, while others tested the effects of exogenous microbes as probiotics or for substrate pre-processing to improve larval fitness, bioconversion rates, or nutritional qualities. This review examined all peer-reviewed literature on these topics to consolidate many disparate findings together. It followed the PRISMA guidelines for scoping reviews. The results found no evidence of globally conserved core microbes, as diet strongly correlated with gut microbiome, but some genera appeared most frequently in BSF larval guts worldwide regardless of diet. The gut microbes undoubtably assist in digestion, including pathogen suppression, and so microbial probiotics show promise for future investigations. However, the common gut microbes have not been explored as probiotics themselves, which would be a promising direction for future work. The impacts of BSF bioconversion on pathogens varied, so each rearing facility should investigate and manage their pathogen risks independently. The data summarized in this study provide useful reference points for future investigations into BSF–microbe interactions.

Modulation of Microbiota and its Impact on Depression

Gut microbial flora is the largest micro-ecosystem in the human body, it is symbiotically associated with the host; and maintains normal physiological processes in a dynamic equilibrium state. A plethora of evidence supports that gut microbial flora influences the neurotransmitters of the central nervous system. This gut flora influences cognitive function, anxiety, depression; and mood disorders as they are capable of synthesizing neurotransmitters in the nervous system. Therefore intake of probiotics influences gut microbiome; and depression. The versatility and number of gut microbial flora varies individually, so the content of common gut microbes may affect the neurotransmitters, manipulating the gut microbiota with probiotics offers a novel approach to treat brain disorders such as depression via GUT-BRAIN AXIS. The present review outlines the aspect of such alterations and how modulation of gut microbiota influences depression.

Acarbose Impairs Gut Bacteroides Growth by Targeting Intracellular GH97 Enzymes.

Acarbose is a type-2 diabetes medicine that inhibits dietary starch breakdown into glucose by inhibiting host amylase and glucosidase enzymes. Numerous gut species in the Bacteroides genus enzymatically break down starch and change in relative abundance within the gut microbiome in acarbose-treated individuals. To mechanistically explain this observation, we used two model starch-degrading Bacteroides, Bacteroides ovatus (Bo) and Bacteroides thetaiotaomicron (Bt). Bt growth is severely impaired by acarbose whereas Bo growth is not. The Bacteroides use a starch utilization system (Sus) to grow on starch. We hypothesized that Bo and Bt Sus enzymes are differentially inhibited by acarbose. Instead, we discovered that although acarbose primarily targets the Sus periplasmic GH97 enzymes in both organisms, the drug affects starch processing at multiple other points. Acarbose competes for transport through the Sus beta-barrel proteins and binds to the Sus transcriptional regulators. Further, Bo expresses a non-Sus GH97 (BoGH97D) when grown in starch with acarbose. The Bt homolog, BtGH97H, is not expressed in the same conditions, nor can overexpression of BoGH97D complement the Bt growth inhibition in the presence of acarbose. This work informs us about unexpected complexities of Sus function and regulation in Bacteroides, including variation between related species. Further, this indicates that the gut microbiome may be a source of variable response to acarbose treatment for diabetes.

Effects of glycyrrhizin, stevioside, and sucralose on the growth and metabolism of the omnipresent gut commensal Escherichia coli

The rise in popularity of non-caloric sweeteners (NCS) among obese and diabetic patients is due to their ability to provide a sweet taste without any caloric input. However, NCS consumption may be linked to metabolic disorders. The mechanisms behind these adverse effects are still unclear, which suggests that NCS may alter the metabolic activity of the gut microbiome, leading to enteric environmental perturbation and resulting in physiological anomalies in the host. This study investigates how Escherichia coli, a common gut microbe, reacts to three NCS, two of which come from nature (glycyrrhizin and stevioside) and one that is made artificially (sucralose). To assess the impact of these NCS, this study investigated the growth, gene expression, and metabolic pathways of E. coli under different sweetener loads. Compared to the untreated control, low amounts of glycyrrhizin made E. coli grow faster, while similar amounts of sucralose and stevioside had no or a less noticeable effect. At higher concentrations, these sweeteners slowed down or inhibited the growth of the bacteria. Thus, NCS may have dose-dependent impacts on gut microbes. After treatment with amounts that corresponded to the acceptable daily intake, the expression of key metabolic genes showed altered expression, which may potentially affect their metabolism. At different concentrations of the NCS, there were clear differences in the global metabolomic profile between the control and the different NCS treatments. Under in vitro conditions, glycyrrhizin and sucralose appeared to have a less divergent impact on E. coli growth, gene expression, and metabolism, which may suggest that these are relatively safer sugar substitutes for humans.

Mobilization of vitamin B12 transporters alters competitive dynamics in a human gut microbe

SUMMARYThe functional and genomic diversity of the human gut microbiome is shaped by horizontal transfer of mobile genetic elements (MGEs). Characterized MGEs can encode genes beneficial for their host’s self-defense (e.g., antibiotic resistance) or ability to compete for essential or limited resources (e.g., vitamins). Vitamin B12 and related compounds (corrinoids) are critical nutrients that enable colonization by members of the common gut microbe phylum, the Bacteroidetes. Herein, we identify a distinct class of MGEs in the Bacteroidetes responsible for the mobilization and exchange of the genes required for transport of corrinoids, a group of cyclic tetrapyrrole cofactors including vitamin B12 (btuGBFCD). This class includes two distinct groups of conjugative transposons (CTns) and one group of phage. Conjugative transfer and vitamin B12 transport activity of two of the CTns were confirmed in vitro and in vivo, demonstrating the important role MGEs play in distribution of corrinoid transporters in the Bacteroidetes.

Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3

Culture-independent analyses of microbial communities have progressed dramatically in the last decade, particularly due to advances in methods for biological profiling via shotgun metagenomics. Opportunities for improvement continue to accelerate, with greater access to multi-omics, microbial reference genomes, and strain-level diversity. To leverage these, we present bioBakery 3, a set of integrated, improved methods for taxonomic, strain-level, functional, and phylogenetic profiling of metagenomes newly developed to build on the largest set of reference sequences now available. Compared to current alternatives, MetaPhlAn 3 increases the accuracy of taxonomic profiling, and HUMAnN 3 improves that of functional potential and activity. These methods detected novel disease-microbiome links in applications to CRC (1262 metagenomes) and IBD (1635 metagenomes and 817 metatranscriptomes). Strain-level profiling of an additional 4077 metagenomes with StrainPhlAn 3 and PanPhlAn 3 unraveled the phylogenetic and functional structure of the common gut microbe Ruminococcus bromii, previously described by only 15 isolate genomes. With open-source implementations and cloud-deployable reproducible workflows, the bioBakery 3 platform can help researchers deepen the resolution, scale, and accuracy of multi-omic profiling for microbial community studies.

Serotonin helps gut bacteria colonize

From the crowded confines of the intestine comes new research about a bacterial species that uses serotonin from the gut to gain an upper hand in its quest to colonize and survive. In studies done in mice, a team of researchers found that Turicibacter sanguinis, a common gut microbe, can signal nearby intestinal cells to release serotonin, a neurotransmitter typically associated with mammalian mood and digestion (Nat. Microbiol. 2019, DOI: 10.1038/s41564-019-0540-4). When the bacteria take up serotonin, the small molecule prompts the expression of genes related to growth and survival, allowing the microbes to colonize the host’s gut, says Elaine Hsiao, the lead researcher on the project at the University of California, Los Angeles. Treating the mice with fluoxetine, sold as Prozac, blocks serotonin uptake and prevents T. sanguinis from colonizing the animals. The Prozac findings may help explain some of the drug’s gastrointestinal side effects, Hsiao says. Mice, human,

Enterococcus faecalis Sex Pheromone cCF10 Enhances Conjugative Plasmid Transfer In Vivo.

ABSTRACTCell-cell communication mediated by peptide pheromones (cCF10 [CF]) is essential for high-frequency plasmid transfer in vitro in Enterococcus faecalis. To examine the role of pheromone signaling in vivo, we established either a CF-producing (CF+) recipient or a recipient producing a biologically inactive variant of CF (CF− recipient) in a germfree mouse model 3 days before donor inoculation and determined transfer frequencies of the pheromone-inducible plasmid pCF10. Plasmid transfer was detected in the upper and middle sections of the intestinal tract 5 h after donor inoculation and was highly efficient in the absence of antibiotic selection. The transconjugant/donor ratio reached a maximum level approaching 1 on day 4 in the upper intestinal tract. Plasmid transfer was significantly lower with the CF− recipient. While rescue of the CF− mating defect by coculture with CF+ recipients is easily accomplished in vitro, no extracellular complementation occurred in vivo. This suggests that most pheromone signaling in the gut occurs between recipient and donor cells in very close proximity. Plasmid-bearing cells (donors plus transconjugants) steadily increased in the population from 0.1% after donor inoculation to about 10% at the conclusion of the experiments. This suggests a selective advantage of pCF10 carriage distinct from antibiotic resistance or bacteriocin production. Our results demonstrate that pheromone signaling is required for efficient pCF10 transfer in vivo. In the absence of CF+ recipients, a low level of transfer to CF− recipients occurred in the gut. This may result from low-level host-mediated induction of the donors in the gastrointestinal (GI) tract, similar to that previously observed in serum.

Coadministration of the Campylobacter jejuni N-Glycan-Based Vaccine with Probiotics Improves Vaccine Performance in Broiler Chickens.

Source attribution studies report that the consumption of contaminated poultry is the primary source for acquiring human campylobacteriosis. Oral administration of an engineered Escherichia coli strain expressing the Campylobacter jejuni N-glycan reduces bacterial colonization in specific-pathogen-free leghorn chickens, but only a fraction of birds respond to vaccination. Optimization of the vaccine for commercial broiler chickens has great potential to prevent the entry of the pathogen into the food chain. Here, we tested the same vaccination approach in broiler chickens and observed similar efficacies in pathogen load reduction, stimulation of the host IgY response, the lack of C. jejuni resistance development, uniformity in microbial gut composition, and the bimodal response to treatment. Gut microbiota analysis of leghorn and broiler vaccine responders identified one member of Clostridiales cluster XIVa, Anaerosporobacter mobilis, that was significantly more abundant in responder birds. In broiler chickens, coadministration of the live vaccine with A. mobilis or Lactobacillus reuteri, a commonly used probiotic, resulted in increased vaccine efficacy, antibody responses, and weight gain. To investigate whether the responder-nonresponder effect was due to the selection of a C. jejuni "supercolonizer mutant" with altered phase-variable genes, we analyzed all poly(G)-containing loci of the input strain compared to nonresponder colony isolates and found no evidence of phase state selection. However, untargeted nuclear magnetic resonance (NMR)-based metabolomics identified a potential biomarker negatively correlated with C. jejuni colonization levels that is possibly linked to increased microbial diversity in this subgroup. The comprehensive methods used to examine the bimodality of the vaccine response provide several opportunities to improve the C. jejuni vaccine and the efficacy of any vaccination strategy.IMPORTANCECampylobacter jejuni is a common cause of human diarrheal disease worldwide and is listed by the World Health Organization as a high-priority pathogen. C. jejuni infection typically occurs through the ingestion of contaminated chicken meat, so many efforts are targeted at reducing C. jejuni levels at the source. We previously developed a vaccine that reduces C. jejuni levels in egg-laying chickens. In this study, we improved vaccine performance in meat birds by supplementing the vaccine with probiotics. In addition, we demonstrated that C. jejuni colonization levels in chickens are negatively correlated with the abundance of clostridia, another group of common gut microbes. We describe new methods for vaccine optimization that will assist in improving the C. jejuni vaccine and other vaccines under development.

The Common Gut Microbe Eubacterium hallii also Contributes to Intestinal Propionate Formation.

Eubacterium hallii is considered an important microbe in regard to intestinal metabolic balance due to its ability to utilize glucose and the fermentation intermediates acetate and lactate, to form butyrate and hydrogen. Recently, we observed that E. hallii is capable of metabolizing glycerol to 3-hydroxypropionaldehyde (3-HPA, reuterin) with reported antimicrobial properties. The key enzyme for glycerol to 3-HPA conversion is the cobalamin-dependent glycerol/diol dehydratase PduCDE which also utilizes 1,2-propanediol (1,2-PD) to form propionate. Therefore our primary goal was to investigate glycerol to 3-HPA metabolism and 1,2-PD utilization by E. hallii along with its ability to produce cobalamin. We also investigated the relative abundance of E. hallii in stool of adults using 16S rRNA and pduCDE based gene screening to determine the contribution of E. hallii to intestinal propionate formation. We found that E. hallii utilizes glycerol to produce up to 9 mM 3-HPA but did not further metabolize 3-HPA to 1,3-propanediol. Utilization of 1,2-PD in the presence and absence of glucose led to the formation of propanal, propanol and propionate. E. hallii formed cobalamin and was detected in stool of 74% of adults using 16S rRNA gene as marker gene (n = 325). Relative abundance of the E. hallii 16S rRNA gene ranged from 0 to 0.59% with a mean relative abundance of 0.044%. E. hallii PduCDE was detected in 63 to 81% of the metagenomes depending on which subunit was investigated beside other taxons such as Ruminococcus obeum, R. gnavus, Flavonifractor plautii, Intestinimonas butyriciproducens, and Veillonella spp. In conclusion, we identified E. hallii as a common gut microbe with the ability to convert glycerol to 3-HPA, a step that requires the production of cobalamin, and to utilize 1,2-PD to form propionate. Our results along with its ability to use a broad range of substrates point at E. hallii as a key species within the intestinal trophic chain with the potential to highly impact the metabolic balance as well as the gut microbiota/host homeostasis by the formation of different short chain fatty acids.

Microbiota and the gut-brain axis.

Changes in gut microbiota can modulate the peripheral and central nervous systems, resulting in altered brain functioning, and suggesting the existence of a microbiota gut-brain axis. Diet can also change the profile of gut microbiota and, thereby, behavior. Effects of bacteria on the nervous system cannot be disassociated from effects on the immune system since the two are in constant bidirectional communication. While the composition of the gut microbiota varies greatly among individuals, alterations to the balance and content of common gut microbes may affect the production of molecules such as neurotransmitters, e.g., gamma amino butyric acid, and the products of fermentation, e.g., the short chain fatty acids butyrate, propionate, and acetate. Short chain fatty acids, which are pleomorphic, especially butyrate, positively influence host metabolism by promoting glucose and energy homeostasis, regulating immune responses and epithelial cell growth, and promoting the functioning of the central and peripheral nervous systems. In the future, the composition, diversity, and function of specific probiotics, coupled with similar, more detailed knowledge about gut microbiota, will potentially help in developing more effective diet- and drug-based therapies.

Common gut microbe could help prevent development of multiple sclerosis

Common gut microbe could help prevent development of multiple sclerosis

Immunohistochemical search for viral and bacterial antigens in Crohn's disease

BackgroundRecent studies show that diseased intestinal tissues of patients with Crohn's disease (CD) contain obstructed lymphatics, granulomas, and tertiary lymphoid organs, representing responses to persistent antigen. MethodsForty-seven tissue sections from 28 CD patients and 20 tissue sections from 17 control patients were studied. Tissues were immunostained with antibody directed against adenovirus, Epstein-Barr virus, herpes simplex virus I, parvovirus B19, Listeria monocytogenes, Escherichia coli, Clostridium perfringens, and Mycobacterium avium subspecies paratuberculosis. ResultsThere was no evidence of adenovirus, Epstein-Barr virus, parvovirus B19, or M. avium subsp. paratuberculosis in the tissues. Clostridia were positively stained in the mucus of 18.5% of CD patients versus 35.3% of controls and in the tissue of 11.1% of CD patients but in no controls.Immunoreactivity to listeria antibody occurred in the mucus of 3.7% of CD patients and in 5.9% of controls while it occurred in the tissue of 37.0% of CD patients and 29.4% of controls. E. coli occurred in the mucus of 48.1% CD and 64.7% controls and in the tissue of 18.5% and 5.9% respectively. ConclusionsOf the agents demonstrated in this search, none was located in granulomas or inflamed lymphatics. Finding the common gut microbes, E. coli and clostridia, in the mucus of patients and controls was not unexpected. The minor focal staining of E. coli and clostridia does not suggest a primary role for these pathogens in CD. Positive staining for listeria in patients and controls may very well represent cross reactivity rather than specific identification.

Analytical performance of a PCR assay for the detection of KRAS mutations (codons 12/13 and 61) in formalin-fixed paraffin-embedded tissue samples of colorectal carcinoma

KRAS mutation testing is mandatory before prescribing anti-epidermal growth factor monoclonal antibodies in the treatment of advanced colorectal cancer. We describe the performance of a TaqMelt polymerase chain reaction (PCR) assay—the cobas® KRAS Mutation Test—designed to detect 19 mutations in codons 12, 13, and 61. The limit of detection was determined using DNA blends from cell lines, plasmids, and formalin-fixed paraffin-embedded tissue specimens. Assay performance was compared to Sanger sequencing using a panel of 188 specimens. Discordant specimens were subjected to next generation pyrosequencing (454). Assay repeatability was assessed using a panel of six specimens. A >95% correct mutation call rate was obtained in all specimen types with ~5% mutant alleles at DNA inputs of 0.8–6.3 ng per PCR reaction; 100% detection rate was observed at the recommended DNA input of 50 ng. The positive percent agreement with Sanger was 97.5% (79/81) for codons 12/13 and 85.7% (6/7) for codon 61. Negative percent agreement was 94.4% (101/107) for codon 12/13 and 99.4% (180/181) for codon 61. Nine of 10 discordant specimens yielded 454 results consistent with the cobas® results. With repeated testing, the assay showed a correct call rate of 100% (192/192) for all operators, instruments, reagent lots, and days tested. The cobas® test detects KRAS mutations in codons 12, 13, and 61 at a limit of detection of <5%. The PCR assay was more sensitive and specific than Sanger sequencing, and performance was highly reproducible. Test performance was not influenced by various endogenous interfering substances or common gut microbes.