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Nature Communications Oct 2023Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the... (Meta-Analysis)
Meta-Analysis
Malaria is caused by Plasmodium species and remains a significant cause of morbidity and mortality globally. Gut bacteria can influence the severity of malaria, but the contribution of specific bacteria to the risk of severe malaria is unknown. Here, multiomics approaches demonstrate that specific species of Bacteroides are causally linked to the risk of severe malaria. Plasmodium yoelii hyperparasitemia-resistant mice gavaged with murine-isolated Bacteroides fragilis develop P. yoelii hyperparasitemia. Moreover, Bacteroides are significantly more abundant in Ugandan children with severe malarial anemia than with asymptomatic P. falciparum infection. Human isolates of Bacteroides caccae, Bacteroides uniformis, and Bacteroides ovatus were able to cause susceptibility to severe malaria in mice. While monocolonization of germ-free mice with Bacteroides alone is insufficient to cause susceptibility to hyperparasitemia, meta-analysis across multiple studies support a main role for Bacteroides in susceptibility to severe malaria. Approaches that target gut Bacteroides present an opportunity to prevent severe malaria and associated deaths.
Topics: Child; Humans; Animals; Mice; Microbial Consortia; Malaria; Bacteroides; Bacteroides fragilis; Anemia; Plasmodium yoelii
PubMed: 37833304
DOI: 10.1038/s41467-023-42235-0 -
Neoplasia (New York, N.Y.) Sep 2023Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in... (Review)
Review
BACKGROUND
Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ICI would be valuable. This systematic review aimed to investigate the association between fecal gut microbiota composition and ICI-treatment response in patients with cancer.
METHODS
EMBASE, Medline, and Cochrane Library databases were searched using the "Participants, Interventions, Comparisons, and Outcomes" (PICO) process to locate studies including participants with solid cancers treated with ICI intervention. The comparator was the gut microbiota, and the outcomes were oncological outcomes such as response rates and progression-free survival. Study data were synthesized qualitatively in a systematic narrative synthesis, and the risk of bias in the studies was assessed.
RESULTS
Two reviewers screened 2092 abstracts independently, and 140 studies were read as full-text reports and assessed for eligibility. Eighteen studies were included with 775 patients with different types of solid cancers who received anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Distinct patterns were observed in the patients' fecal samples. Some bacterial species were reported to be present in responders and non-responders, while others were present only in one group. The most reported species associated with better prognosis were Faecalibacterium prausnitzii, Streptococcus parasanguinis, Bacteroides caccae, and Prevotella copri. In contrast, the most reported species associated with poor prognosis were Blautia obeum and Bacteroides ovatus.
CONCLUSION
Distinct microbiota features were associated with good and poor prognoses in ICI-treated patients with cancer.
Topics: Humans; Gastrointestinal Microbiome; Microbiota; Databases, Factual
PubMed: 37603952
DOI: 10.1016/j.neo.2023.100923 -
Frontiers in Cellular and Infection... 2023This study aims to investigate the composition and function of the gut microbiome in long-term depression using an 8-week chronic unpredictable mild stress (CUMS) rat...
OBJECTIVE
This study aims to investigate the composition and function of the gut microbiome in long-term depression using an 8-week chronic unpredictable mild stress (CUMS) rat model.
MATERIALS AND METHODS
Animals were sacrificed after either 4 weeks or 8 weeks under CUMS to mimic long-term depression in humans. The gut microbiome was analyzed to identify potential depression-related gut microbes, and the fecal metabolome was analyzed to detect their functional metabolites. The correlations between altered gut microbes and metabolites in the long-term depression rats were explored. The crucial metabolic pathways related to long-term depression were uncovered through enrichment analysis based on these gut microbes and metabolites.
RESULTS
The microbial composition of long-term depression (8-week CUMS) showed decreased species richness indices and different profiles compared with the control group and the 4-week CUMS group, characterized by disturbance of Alistipes indistinctus, Bacteroides ovatus, and Alistipes senegalensis at the species level. Additionally, long-term depression was associated with disturbances in fecal metabolomics. D-pinitol was the only increased metabolite in the 8-week CUMS group among the top 10 differential metabolites, while the top 3 decreased metabolites in the long-term depression rats included indoxyl sulfate, trimethylaminen-oxide, and 3 alpha,7 alpha-dihydroxy-12-oxocholanoic acid. The disordered fecal metabolomics in the long-term depression rats mainly involved the biosynthesis of pantothenate, CoA, valine, leucine and isoleucine.
CONCLUSION
Our findings suggest that the gut microbiome may participate in the long-term development of depression, and the mechanism may be related to the regulation of gut metabolism.
Topics: Humans; Rats; Animals; Gastrointestinal Microbiome; Depression; Metabolomics; Metabolome; Feces
PubMed: 37051300
DOI: 10.3389/fcimb.2023.1116277 -
Cellular and Molecular Life Sciences :... Jul 2023Members of the Bacteroidetes phylum in the human colon deploy an extensive number of proteins to capture and degrade polysaccharides. Operons devoted to glycan breakdown...
Members of the Bacteroidetes phylum in the human colon deploy an extensive number of proteins to capture and degrade polysaccharides. Operons devoted to glycan breakdown and uptake are termed polysaccharide utilization loci or PUL. The starch utilization system (Sus) is one such PUL and was initially described in Bacteroides thetaiotaomicron (Bt). BtSus is highly conserved across many species, except for its extracellular α-amylase, SusG. In this work, we show that the Bacteroides ovatus (Bo) extracellular α-amylase, BoGH13A, is distinguished from SusG in its evolutionary origin and its domain architecture and by being the most prevalent form in Bacteroidetes Sus. BoGH13A is the founding member of both a novel subfamily in the glycoside hydrolase family 13, GH13_47, and a novel carbohydrate-binding module, CBM98. The BoGH13A CBM98-CBM48-GH13_47 architecture differs from the CBM58 embedded within the GH13_36 of SusG. These domains adopt a distinct spatial orientation and invoke a different association with the outer membrane. The BoCBM98 binding site is required for Bo growth on polysaccharides and optimal enzymatic degradation thereof. Finally, the BoGH13A structure features bound Ca and Mn ions, the latter of which is novel for an α-amylase. Little is known about the impact of Mn on gut bacterial function, much less on polysaccharide consumption, but Mn addition to Bt expressing BoGH13A specifically enhances growth on starch. Further understanding of bacterial starch degradation signatures will enable more tailored prebiotic and pharmaceutical approaches that increase starch flux to the gut.
Topics: Humans; alpha-Amylases; Bacteroides; Starch; Polysaccharides
PubMed: 37500984
DOI: 10.1007/s00018-023-04812-w -
Cell Surface Xyloglucan Recognition and Hydrolysis by the Human Gut Commensal Bacteroides uniformis.Applied and Environmental Microbiology Jan 2022Xyloglucan (XyG) is a ubiquitous plant cell wall hemicellulose that is targeted by a range of syntenic, microheterogeneous xyloglucan utilization loci (XyGUL) in... (Review)
Review
Xyloglucan (XyG) is a ubiquitous plant cell wall hemicellulose that is targeted by a range of syntenic, microheterogeneous xyloglucan utilization loci (XyGUL) in species of the human gut microbiota (HGM), including Bacteroides ovatus and B. uniformis. Comprehensive biochemical and biophysical analyses have identified key differences in the protein complements of each locus that confer differential access to structurally diverse XyG side chain variants. A second, nonsyntenic XyGUL was previously identified in B. uniformis, although its function in XyG utilization compared to its syntenic counterpart was unclear. Here, complementary enzymatic product profiles and bacterial growth curves showcase the notable preference of XyGUL2 surface glycan-binding proteins (SGBPs) to bind full-length XyG, as well as a range of oligosaccharides produced by the glycoside hydrolase family 5 (GH5_4) -xyloglucanase from this locus. We use isothermal titration calorimetry (ITC) to characterize this binding capacity and pinpoint the specific contributions of each protein to nutrient capture. The high-resolution structure of XyGUL2 SGBP-B reveals remarkable putative binding site conservation with the canonical XyG-binding XyGUL SGBP-B, supporting similar roles for these proteins in glycan capture. Together, these data underpin the central role of complementary XyGUL function in B. uniformis and broaden our systems-based and mechanistic understanding of XyG utilization in the HGM. The omnipresence of xyloglucans in the human diet has led to the evolution of heterogeneous gene clusters in several species in the HGM, each specially tuned to respond to the structural variations of these complex plant cell wall polysaccharides. Our research illuminates the complementary roles of syntenic and nonsyntenic XyGUL in B. uniformis in conferring growth on a variety of XyG-derived substrates, providing evidence of glycan-binding protein microadaptation within a single species. These data serve as a comprehensive overview of the binding capacities of the SGBPs from a nonsyntenic B. uniformis XyGUL and will inform future studies on the roles of complementary loci in glycan targeting by key HGM species.
Topics: Bacteroides; Gastrointestinal Tract; Glucans; Humans; Hydrolysis; Xylans
PubMed: 34731054
DOI: 10.1128/AEM.01566-21 -
Cureus Jul 2022The authors present the case of a 29-year-old female diagnosed with acute appendicitis who underwent an uneventful laparoscopic appendectomy. Three weeks later, she...
The authors present the case of a 29-year-old female diagnosed with acute appendicitis who underwent an uneventful laparoscopic appendectomy. Three weeks later, she returned to the emergency department with fevers, abdominal pain, chills, and nausea. Laboratory analysis revealed elevated liver enzymes and leukocytosis, and a computed tomography scan of the abdomen revealed a liver abscess. Interventional radiology placed an 8 French drainage catheter in the hepatic abscess and drained 40cc of purulent fluid. A culture of the abscess fluid revealed Streptococcus constellatus, Bacteroides fragilis, and Bacteroides ovatus. We believe appendicitis causes hematogenous spreading of bowel organisms along the portal vein, which is seeded to the liver.
PubMed: 35978753
DOI: 10.7759/cureus.26867 -
Gut Microbes 2019: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined -based bacteriotherapy could... (Comparative Study)
Comparative Study
: Bacteriotherapy aimed at addressing dysbiosis may be therapeutic for Inflammatory Bowel Diseases (IBDs). We sought to determine if defined -based bacteriotherapy could be an effective and consistent alternative to fecal microbiota transplantation (FMT) in a murine model of IBD. : We induced experimental colitis in 8- 12-week-old C57BL/6 mice using 2-3% dextran sodium sulfate. Mice were simultaneously treated by oral gavage with a triple- cocktail, individual strains, FMT using stool from healthy donor mice, or their own stool as a control. Survival, weight loss and markers of inflammation (histology, serum amyloid A, cytokine production) were correlated to gene profiling of fecal and mucosal microbiomes. : Triple- combination therapy was more protective against weight loss and mortality than traditional FMT therapy. ATCC8483 was more effective than any individual strain, or a combination of strains, in preventing weight loss, decreasing histological damage, dampening inflammatory response, and stimulating epithelial recovery. Irrespective of the treatment group, overall abundance associated with treatment success and decreased cytokine production while the presence of correlated with treatment failure. However, the therapeutic benefit associated with high abundance was negated in the presence of . : monotherapy was more consistent and effective than traditional FMT at ameliorating colitis and stimulating epithelial recovery in a murine model of IBD. Given the tolerability of ATCC 8483 in an active, on-going human study, this therapy may be repurposed for the management of IBD in a clinically expedient timeline.
Topics: Animals; Bacteria; Bacteroides; Colitis; Dextran Sulfate; Disease Models, Animal; Fecal Microbiota Transplantation; Feces; Gastrointestinal Tract; Inflammation; Male; Mice, Inbred C57BL; RNA, Ribosomal, 16S; Survival Analysis; Treatment Outcome
PubMed: 30663928
DOI: 10.1080/19490976.2018.1560753 -
Frontiers in Microbiology 2021Bacteroidetes are the most common bacterial phylum in the mammalian intestine and the effects of several spp. on multiple facets of host physiology have been...
Bacteroidetes are the most common bacterial phylum in the mammalian intestine and the effects of several spp. on multiple facets of host physiology have been previously described. Of the spp., has recently garnered attention due to its beneficial effects in the context of intestinal inflammation. In this study, we aimed to examine model host intestinal physiological conditions and dietary modifications to characterize their effects on growth. Using Biolog phenotypic microarrays, we evaluated 62 primary carbon sources and determined that ATCC 8384 can use the following carbohydrates as primary carbon sources: 10 disaccharides, 4 trisaccharides, 4 polysaccharides, 4 polymers, 3 L-linked sugars, 6 D-linked sugars, 5 amino-sugars, 6 alcohol sugars, and 15 organic acids. Proteomic profiling of bacteria revealed that a significant portion of the proteome contains proteins important for metabolism. Among the proteins, we found glycosyl hydrolase (GH) familes GH2, GH5, GH20, GH 43, GH88, GH92, and GH95. We also identified multiple proteins with antioxidant properties and reasoned that these proteins may support growth in the GI tract. Upon further testing, we showed that grew robustly in various pH, osmolarity, bile, ethanol, and HO concentrations; indicating that is a well-adapted gut microbe. Taken together, we have demonstrated that key host and diet-derived changes in the intestinal environment influence growth. These data provide the framework for future work toward understanding how diet and lifestyle interventions may promote a beneficial environment for growth.
PubMed: 34899632
DOI: 10.3389/fmicb.2021.745469 -
Frontiers in Microbiology 2022β-glucuronidases (GUS) of intestinal bacteria remove glucuronic acid from glucoronides, reversing phase II metabolism of the liver and affecting the level of active...
β-glucuronidases (GUS) of intestinal bacteria remove glucuronic acid from glucoronides, reversing phase II metabolism of the liver and affecting the level of active deconjugated metabolites deriving from drugs or xenobiotics. Two hundred seventy-nine non-redundant GUS sequences are known in the gut microbiota, classified in seven structural categories (NL, L1, L2, mL1, mL2, mL1,2, and NC) with different biocatalytic properties. In the present study, the intestinal metagenome of 60 healthy subjects from five geographically different cohorts was assembled, binned, and mined to determine qualitative and quantitative differences in GUS profile, potentially affecting response to drugs and xenobiotics. Each metagenome harbored 4-70 different GUS, altogether accounting for 218. The amount of intestinal bacteria with at least one GUS gene was highly variable, from 0.7 to 82.2%, 25.7% on average. No significant difference among cohorts could be identified, except for the Ethiopia (ETH) cohort where GUS-encoding bacteria were significantly less abundant. The structural categories were differently distributed among the metagenomes, but without any statistical significance related to the cohorts. GUS profiles were generally dominated by the category NL, followed by mL1, L2, and L1. The GUS categories most involved in the hydrolysis of small molecules, including drugs, are L1 and mL1. Bacteria contributing to these categories belonged to , , , , , , , and . Bacteria harboring L1 GUS were generally scarcely abundant (<1.3%), except in three metagenomes, where they reached up to 24.3% for the contribution of and Bacteria harboring mL1 GUS were significantly more abundant (mean = 4.6%), with representing a major contributor. Albeit mL1 enzymes are less active than L1 ones, likely plays a pivotal role in the deglucuronidation, due to its remarkable abundance in the microbiomes. The observed broad interindividual heterogeneity of GUS profiles, particularly of the L1 and mL1 categories, likely represent a major driver of pharmacomicrobiomics variability, affecting drug response and toxicity. Different geographical origins, genetic, nutritional, and lifestyle features of the hosts seemed not to be relevant in the definition of glucuronidase activity, albeit they influenced the richness of the GUS profile.
PubMed: 35308380
DOI: 10.3389/fmicb.2022.826994 -
MSystems Feb 2022Symbiotic bacteria are responsible for the majority of complex carbohydrate digestion in the human colon. Since the identities and amounts of dietary polysaccharides...
Symbiotic bacteria are responsible for the majority of complex carbohydrate digestion in the human colon. Since the identities and amounts of dietary polysaccharides directly impact the gut microbiota, determining which microorganisms consume specific nutrients is central for defining the relationship between diet and gut microbial ecology. Using a custom phenotyping array, we determined carbohydrate utilization profiles for 354 members of the , a dominant saccharolytic phylum. There was wide variation in the numbers and types of substrates degraded by individual bacteria, but phenotype-based clustering grouped members of the same species indicating that each species performs characteristic roles. The ability to utilize dietary polysaccharides and endogenous mucin glycans was negatively correlated, suggesting exclusion between these niches. By analyzing related Bacteroides ovatusBacteroides xylanisolvens strains that vary in their ability to utilize mucin glycans, we addressed whether gene clusters that confer this complex, multilocus trait are being gained or lost in individual strains. Pangenome reconstruction of these strains revealed a remarkably mosaic architecture in which genes involved in polysaccharide metabolism are highly variable and bioinformatics data provide evidence of interspecies gene transfer that might explain this genomic heterogeneity. Global transcriptomic analyses suggest that the ability to utilize mucin has been lost in some lineages of and , which harbor residual gene clusters that are involved in mucin utilization by strains that still actively express this phenotype. Our data provide insight into the breadth and complexity of carbohydrate metabolism in the microbiome and the underlying genomic events that shape these behaviors. Nonharmful bacteria are the primary microbial symbionts that inhabit the human gastrointestinal tract. These bacteria play many beneficial roles and in some cases can modify disease states, making it important to understand which nutrients sustain specific lineages. This knowledge will in turn lead to strategies to intentionally manipulate the gut microbial ecosystem. We designed a scalable, high-throughput platform for measuring the ability of gut bacteria to utilize polysaccharides, of which many are derived from dietary fiber sources that can be manipulated easily. Our results provide paths to expand phenotypic surveys of more diverse gut bacteria to understand their functions and also to leverage dietary fibers to alter the physiology of the gut microbial community.
Topics: Humans; Polysaccharides; Bacteria; Dietary Carbohydrates; Microbiota; Dietary Fiber; Genomics; Mucins
PubMed: 35166563
DOI: 10.1128/msystems.00947-21