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PLoS Biology May 2023In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We...
In the human gut, the growth of the pathogen Clostridioides difficile is impacted by a complex web of interspecies interactions with members of human gut microbiota. We investigate the contribution of interspecies interactions on the antibiotic response of C. difficile to clinically relevant antibiotics using bottom-up assembly of human gut communities. We identify 2 classes of microbial interactions that alter C. difficile's antibiotic susceptibility: interactions resulting in increased ability of C. difficile to grow at high antibiotic concentrations (rare) and interactions resulting in C. difficile growth enhancement at low antibiotic concentrations (common). Based on genome-wide transcriptional profiling data, we demonstrate that metal sequestration due to hydrogen sulfide production by the prevalent gut species Desulfovibrio piger increases the minimum inhibitory concentration (MIC) of metronidazole for C. difficile. Competition with species that display higher sensitivity to the antibiotic than C. difficile leads to enhanced growth of C. difficile at low antibiotic concentrations due to competitive release. A dynamic computational model identifies the ecological principles driving this effect. Our results provide a deeper understanding of ecological and molecular principles shaping C. difficile's response to antibiotics, which could inform therapeutic interventions.
Topics: Humans; Anti-Bacterial Agents; Gastrointestinal Microbiome; Clostridioides difficile; Clostridioides; Clostridium Infections
PubMed: 37167201
DOI: 10.1371/journal.pbio.3002100 -
Scientific Reports Apr 2022In the present study, we elucidated the effect of grain-based (GB) diet containing both soluble and insoluble fibers and purified ingredients-based (PIB) diet containing...
In the present study, we elucidated the effect of grain-based (GB) diet containing both soluble and insoluble fibers and purified ingredients-based (PIB) diet containing only insoluble fiber, namely cellulose on mice gut microbiome using whole shotgun based metagenomic sequencing. Although the fiber content in both diet types is the same (5%) the presence of soluble fiber only in the GB diet differentiates it from the PIB diet. The taxonomic analysis of sequenced reads reveals a significantly higher enrichment of probiotic Lactobacilli in the GB group as compared to the PIB group. Further, the enhancement of energy expensive cellular processes namely, cell cycle control, cell division, chromosome partitioning, and transcription is observed in the GB group which could be due to the metabolization of the soluble fiber for faster energy production. In contrast, a higher abundance of cellulolytic bacterial community namely, the members of family Lachnospiraceae and Ruminococcaceae and the metabolism functions are found in the PIB group. The PIB group shows a significant increase in host-derived oligosaccharide metabolism functions indicating that they might first target the host-derived oligosaccharides and self-stored glycogen in addition to utilising the available cellulose. In addition to the beneficial microbial community variations, both the groups also exhibited an increased abundance of opportunistic pathobionts which could be due to an overall low amount of fiber in the diet. Furthermore, backtracing analysis identified probiotic members of Lactobacillus, viz., L. crispatus ST1, L. fermentum CECT 5716, L. gasseri ATCC 33323, L. johnsonii NCC 533 and L. reuteri 100-23 in the GB group, while Bilophila wadsworthia 3_1_6, Desulfovibrio piger ATCC 29098, Clostridium symbiosum WAL-14163, and Ruminococcaceae bacterium D16 in the PIB group. These data suggest that Lactobacilli, a probiotic community of microorganisms, are the predominant functional contributors in the gut of GB diet-fed mice, whereas pathobionts too coexisted with commensals in the gut microbiome of the PIB group. Thus at 5% fiber, GB modifies the gut microbial ecology more effectively than PIB and the inclusion of soluble fiber in the GB diet may be one of the primary factors responsible for this impact.
Topics: Animals; Cellulose; Diet; Dietary Fiber; Edible Grain; Lactobacillus; Metagenome; Metagenomics; Mice; Prebiotics
PubMed: 35468931
DOI: 10.1038/s41598-022-10762-3 -
Frontiers in Cellular and Infection... 2020Gut dysbiosis has been associated with several disease outcomes including diabetes in human populations. Currently, there are no studies of the gut microbiome...
Gut dysbiosis has been associated with several disease outcomes including diabetes in human populations. Currently, there are no studies of the gut microbiome composition in relation to type 2 diabetes (T2D) in Africans. Here, we describe the profile of the gut microbiome in non-diabetic adults (controls) and investigate the association between gut microbiota and T2D in urban West Africans. Gut microbiota composition was determined in 291 Nigerians (98 cases, 193 controls) using fecal 16S V4 rRNA gene sequencing done on the Illumina MiSeq platform. Data analysis of operational taxonomic units (OTU) was conducted to describe microbiome composition and identify differences between T2D and controls. The most abundant phyla were , and . , and were significantly lower in cases than controls ( < 0.001). Feature selection analysis identified a panel of 18 OTUs enriched in cases that included . A panel of 17 OTUs that was enriched in the controls included , and . OTUs with strain-level annotation showing the largest fold-change included (logFC = -3.1; = 4.2 × 10), (logFC = -2.5; = 0.005), (logFC = -1.76; = 0.01), all lower in cases. These findings are notable because supplementation with and has been shown to improve hyperglycemia and reduce insulin resistance in murine models. This first investigation of gut microbiome and diabetes in urban Africans shows that T2D is associated with compositional changes in gut microbiota highlighting the possibility of developing strategies to improve glucose control by modifying bacterial composition in the gut.
Topics: Actinobacteria; Bacteroidetes; Black People; Case-Control Studies; Diabetes Mellitus, Type 2; Dysbiosis; Female; Firmicutes; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Nigeria; Urban Health
PubMed: 32158702
DOI: 10.3389/fcimb.2020.00063 -
Biomolecules Jun 2020A comparative study of the kinetic characteristics (specific activity, initial and maximum rate, and affinity for substrates) of key enzymes of assimilatory sulfate...
A comparative study of the kinetic characteristics (specific activity, initial and maximum rate, and affinity for substrates) of key enzymes of assimilatory sulfate reduction (APS reductase and dissimilatory sulfite reductase) in cell-free extracts of sulphate-reducing bacteria (SRB) from various biotopes was performed. The material for the study represented different strains of SRB from various ecotopes. Microbiological (isolation and cultivation), biochemical (free cell extract preparation) and chemical (enzyme activity determination) methods served in defining kinetic characteristics of SRB enzymes. The determined affinity data for substrates (i.e., sulfite) were 10 times higher for SRB strains isolated from environmental (soil) ecotopes than for strains from the human intestine. The maximum rate of APS reductase reached 0.282-0.862 µmol/min×mg of protein that is only 10 to 28% higher than similar initial values. The maximum rate of sulfite reductase for corrosive relevant collection strains and SRB strains isolated from heating systems were increased by 3 to 10 times. A completely different picture was found for the intestinal SRB V in the strains Desulfovibrio piger Vib-7 (0.67 µmol/min × mg protein) and Desulfomicrobium orale Rod-9 (0.45 µmol/min × mg protein). The determinant in the cluster distribution of SRB strains is the activity of the terminal enzyme of dissimilatory sulfate reduction-sulfite reductase, but not APS reductase. The data obtained from the activity of sulfate reduction enzymes indicated the adaptive plasticity of SRB strains that is manifested in the change in enzymatic activity.
Topics: Adenosine Phosphosulfate; Biodegradation, Environmental; Desulfovibrio desulfuricans; Desulfovibrio vulgaris; Hydrogen Sulfide; Oxidoreductases Acting on Sulfur Group Donors
PubMed: 32560561
DOI: 10.3390/biom10060921 -
Microorganisms Aug 2021This study was conducted to compare the infection heterogeneity and cecal microbiota in chicks infected by . Forty-eight 8-d-old female Arbor Acres chicks were...
This study was conducted to compare the infection heterogeneity and cecal microbiota in chicks infected by . Forty-eight 8-d-old female Arbor Acres chicks were challenged with and euthanized 24 h later. The eight chicks with the highest tissue loads were assigned to group S (-susceptible), and the eight chicks with the lowest tissue loads were assigned to group R (-resistant). Chicks in group S showed a higher liver index ( < 0.05), obvious liver lesions, and an decreasing trend for the villus height-to-crypt depth ratio ( < 0.10), compared with those in group R. Gene expression of , , and was higher, whereas that of and was lower ( < 0.05), in chicks of group R relative to those in group S. Separation of the cecal microbial community structure has been found between the two groups. The -susceptible chicks showed higher abundance of pathogenic bacteria ( and ) in their cecal, while was enriched in the cecal of -resistant chicks. In summary, chicks showed heterogeneous responses to infection. Enhanced intestinal barrier function and cecal microbiota structure, especially a higher abundance of , may help chicks resist invasion.
PubMed: 34442784
DOI: 10.3390/microorganisms9081705 -
NPJ Biofilms and Microbiomes Apr 2022The gut microbes play important roles in human longevity and the gut microbiota profile of centenarians shows some unique features from young adults. Nowadays, most...
The gut microbes play important roles in human longevity and the gut microbiota profile of centenarians shows some unique features from young adults. Nowadays, most microbial studies on longevity are commonly based on metagenomic sequencing which may lose information about the functional microbes with extremely low abundance. Here, we combined in-depth metagenomic sequencing and large-scale culturomics to reveal the unique gut microbial structure of a Chinese longevity population, and to explore the possible relationship between intestinal microbes and longevity. Twenty-five healthy Hainan natives were enrolled in the study, including 12 centenarians and 13 senior neighbors. An average of 51.1 Gb raw sequencing data were obtained from individual fecal sample. We assembled 1778 non-redundant metagenomic assembled genomes (MAGs), 33.46% of which cannot be classified into known species. Comparison with the ordinary people in Hainan province, the longevous cohort displayed significantly decreased abundance of butyrate-producing bacteria and largely increased proportion of Escherichia coli, Desulfovibrio piger and Methanobrevibacter smithii. These species showed a constant change with aging. We also isolated 8,030 strains from these samples by large-scale culturomics, most of which belonged to 203 known species as identified by MALDI-TOF. Surprisingly, only 42.17% of the isolated species were also detected by metagenomics, indicating obvious complementarity between these two approaches. Combination of two complement methods, in-depth metagenomic sequencing and culturomics, provides deeper insights into the longevity-related gut microbiota. The uniquely enriched gut microbes in Hainan extreme decades population may help to promote health and longevity.
Topics: Aged, 80 and over; Bacteria; Centenarians; China; Health Promotion; Humans; Longevity; Metagenomics; Microbiota; Young Adult
PubMed: 35440640
DOI: 10.1038/s41522-022-00282-3 -
Journal of Immunology (Baltimore, Md. :... Mar 2018Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in...
Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in cathelin-related antimicrobial peptide (CRAMP) were defective in the development of colon mucosa and highly sensitive to dextran sulfate sodium (DSS)-elicited colitis, as well as azoxymethane-mediated carcinogenesis. Pretreatment of CRAMP mice with antibiotics markedly reduced the severity of DSS-induced colitis, suggesting CRAMP as a limiting factor on dysbiosis in the colon. This was supported by observations that wild-type (WT) mice cohoused with CRAMP mice became highly sensitive to DSS-induced colitis, and the composition of fecal microbiota was skewed by CRAMP deficiency. In particular, several bacterial species that are typically found in oral microbiota, such as , , and , were increased in feces of CRAMP mice and were transferred to WT mice during cohousing. When littermates of CRAMP parents were examined, the composition of the fecal microbiota of WT pups and heterozygous parents was similar. In contrast, although the difference in fecal microbiota between CRAMP and WT pups was small early on after weaning and single mouse housing, there was an increasing divergence with prolonged single housing. These results indicate that CRAMP is critical in maintaining colon microbiota balance and supports mucosal homeostasis, anti-inflammatory responses, and protection from carcinogenesis.
Topics: Animals; Antimicrobial Cationic Peptides; Colitis; Colon; Disease Models, Animal; Feces; Gastrointestinal Microbiome; Homeostasis; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Microbiota; Proteins; Cathelicidins
PubMed: 29440355
DOI: 10.4049/jimmunol.1602073 -
Scientific Reports Sep 2017The aetiology of colic, a functional gastrointestinal disorder in infants, is not yet resolved. Different mechanisms have been suggested involving the gut microbiota and...
The aetiology of colic, a functional gastrointestinal disorder in infants, is not yet resolved. Different mechanisms have been suggested involving the gut microbiota and intermediate metabolites such as lactate. Lactate can be metabolized by lactate-utilizing bacteria (LUB) to form different end-products. Using a functional approach, we hypothesized that H production and accumulation by LUB is associated with the development of colic. The LUB communities in the feces of forty infants, including eight colicky infants, were characterized using a combination of culture- and molecular-based methods, and metabolite concentrations were measured by HPLC. Interactions among LUB strains isolated from feces were investigated with pure and mixed cultures using anaerobic techniques. We emphasized high prevalence of crying, flatulence, colic and positive correlations thereof in the first 3 months of life. Crying infants showed significantly higher ratio of LUB non-sulfate-reducing bacteria (LUB non-SRB) (H-producer), to LUB SRB (H-utilizer) at 3 months. Colicky infants had significantly higher number of H-producing Eubacterium hallii at 2 weeks compared to non-colicky infants. We revealed the function of Desulfovibrio piger and Eubacterium limosum to reduce H accumulation in co-cultures with H-producing Veillonella ratti. Our data suggest that the balance between H-producing and H-utilizing LUB might contribute to colic symptoms.
Topics: Bacteria; Chromatography, High Pressure Liquid; Colic; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Humans; Hydrogen; Infant; Infant, Newborn; Lactic Acid; Male; Metabolome
PubMed: 28894218
DOI: 10.1038/s41598-017-11509-1 -
International Journal of Molecular... Nov 2022Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these...
Links between gut microbiota and autism spectrum disorder (ASD) have been explored in many studies using 16S rRNA gene amplicon and shotgun sequencing. Based on these links, microbiome therapies have been proposed to improve gastrointestinal (GI) and ASD symptoms in ASD individuals. Previously, our open-label microbiota transfer therapy (MTT) study provided insight into the changes in the gut microbial community of children with ASD after MTT and showed significant and long-term improvement in ASD and GI symptoms. Using samples from the same study, the objective of this work was to perform a deeper taxonomic and functional analysis applying shotgun metagenomic sequencing. Taxonomic analyses revealed that ASD Baseline had many bacteria at lower relative abundances, and their abundance increased after MTT. The relative abundance of fiber consuming and beneficial microbes including (, , , ), , and a sulfur reducer increased after MTT-10wks in children with ASD compared to Baseline (consistent at genus level with the previous 16S rRNA gene study). Metabolic pathway analysis at Baseline compared to typically developing (TD) children found an altered abundance of many functional genes but, after MTT, they became similar to TD or donors. Important functional genes that changed included: genes encoding enzymes involved in folate biosynthesis, sulfur metabolism and oxidative stress. These results show that MTT treatment not only changed the relative abundance of important genes involved in metabolic pathways, but also seemed to bring them to a similar level to the TD controls. However, at a two-year follow-up, the microbiota and microbial genes shifted into a new state, distinct from their levels at Baseline and distinct from the TD group. Our current findings suggest that microbes from MTT lead to initial improvement in the metabolic profile of children with ASD, and major additional changes at two years post-treatment. In the future, larger cohort studies, mechanistic in vitro experiments and metatranscriptomics studies are recommended to better understand the role of these specific microbes, functional gene expression, and metabolites relevant to ASD.
Topics: Child; Humans; Autistic Disorder; RNA, Ribosomal, 16S; Autism Spectrum Disorder; Microbiota; Metagenomics; Oxidative Stress; Sulfur
PubMed: 36362265
DOI: 10.3390/ijms232113481 -
Proceedings of the National Academy of... Jun 2006Our colons harbor trillions of microbes including a prominent archaeon, Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we...
Our colons harbor trillions of microbes including a prominent archaeon, Methanobrevibacter smithii. To examine the contributions of Archaea to digestive health, we colonized germ-free mice with Bacteroides thetaiotaomicron, an adaptive bacterial forager of the polysaccharides that we consume, with or without M. smithii or the sulfate-reducing bacterium Desulfovibrio piger. Whole-genome transcriptional profiling of B. thetaiotaomicron, combined with mass spectrometry, revealed that, unlike D. piger, M. smithii directs B. thetaiotaomicron to focus on fermentation of dietary fructans to acetate, whereas B. thetaiotaomicron-derived formate is used by M. smithii for methanogenesis. B. thetaiotaomicron-M. smithii cocolonization produces a significant increase in host adiposity compared with monoassociated, or B. thetaiotaomicron-D. piger biassociated, animals. These findings demonstrate a link between this archaeon, prioritized bacterial utilization of polysaccharides commonly encountered in our modern diets, and host energy balance.
Topics: Animals; Bacteroides; Colon; Desulfovibrio; Diet; Digestion; Fermentation; Fructans; Germ-Free Life; Humans; Methanobrevibacter; Mice; Molecular Sequence Data; Polysaccharides; Symbiosis
PubMed: 16782812
DOI: 10.1073/pnas.0602187103