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Genome Medicine Oct 2019Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have...
BACKGROUND
Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community.
METHODS
In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression.
RESULTS
Higher microbial community richness was associated with longer PFS in 16S and shotgun data (p < 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance of Bacteroides ovatus, Bacteroides dorei, Bacteroides massiliensis, Ruminococcus gnavus, and Blautia producta were related to shorter PFS, and Faecalibacterium prausnitzii, Coprococcus eutactus, Prevotella stercorea, Streptococcus sanguinis, Streptococcus anginosus, and Lachnospiraceae bacterium 3 1 46FAA to longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways of L-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis.
CONCLUSIONS
This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes.
Topics: Aged; Feces; Female; Gastrointestinal Microbiome; Humans; Immunotherapy; Male; Melanoma; Metagenome; Microbiota; RNA, Ribosomal, 16S; Transcriptome
PubMed: 31597568
DOI: 10.1186/s13073-019-0672-4 -
Biomedicine & Pharmacotherapy =... Jan 2022Metformin modifies the gut microbiome in type 2 diabetes and gastrointestinal tolerance to metformin could be mediated by the gut microbiome.
OBJECTIVE
Metformin modifies the gut microbiome in type 2 diabetes and gastrointestinal tolerance to metformin could be mediated by the gut microbiome.
METHODS
We enrolled 35 patients with type 2 diabetes not receiving treatment with metformin due to suspected gastrointestinal intolerance. Metformin was reintroduced at 425 mg, increasing 425 mg every two weeks until reaching 1700 mg per day. According to the occurrence of metformin-related gastrointestinal symptoms, patients were classified into three groups: early intolerance, non-tolerant, and tolerant. Gut microbiota was profiled with 16 S rRNA. This sequencing aimed to determine the differences in the baseline gut microbiota in all groups and prospectively in the tolerant and non-tolerant groups.
RESULTS
The classification resulted in 15 early intolerant, 10 tolerant, and 10 non-tolerant subjects. Early tolerance was characterized by a higher abundance of Subdoligranulum; while Veillonella and Serratia were higher in the non-tolerant group. The tolerant group showed enrichment of Megamonas, Megamonas rupellensis, and Phascolarctobacterium spp; Ruminococcus gnavus was lower in the longitudinal analysis. At the end point Prevotellaceae, Prevotella stercorea, Megamonas funiformis, Bacteroides xylanisolvens, and Blautia producta had a higher relative abundance in the tolerant group compared to the non-tolerant group. Subdoligranulum, Ruminococcus torques_1, Phascolarctobacterium faecium, and Eubacterium were higher in the non-tolerant group. The PICRUSt analysis showed a lower activity of the amino acid biosynthesis pathways and a higher sugar degradation pathway in the intolerant groups.
CONCLUSIONS
Gut microbiota of subjects with gastrointestinal intolerance depicted taxonomic and functional differences compared to tolerant patients, and this changed differently after metformin administration.
Topics: Aged; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Prospective Studies
PubMed: 34844104
DOI: 10.1016/j.biopha.2021.112448 -
Frontiers in Oncology 2021The prognosis of advanced gastrointestinal cancer is poor. There are studies indicating that gut microbes might have the predictive ability to evaluate the outcome of...
OBJECTIVE
The prognosis of advanced gastrointestinal cancer is poor. There are studies indicating that gut microbes might have the predictive ability to evaluate the outcome of cancer therapy, especially immunotherapy. There is limited evidence to date on the influence of microbes on chemotherapeutic response.
DESIGN
In total, 130 patients with advanced or metastatic esophageal (n=40), gastric (n=46), and colorectal cancer (n=44) were enrolled. We included 147 healthy people as controls and used 16S rRNA sequencing to analyze the fecal microbiota.
RESULTS
Significant differences in the abundance of fecal microbiota between patients with gastrointestinal cancer and controls were identified. The abundance of , , , , and were significantly increased in the patient group. , , , , and taxa were significantly more abundant in the controls. The amount of in non-responders (NR) was more likely to decrease significantly after chemotherapy, while the amount mostly increased in responders (R) (=0.040). The optimal abundance variation of may be a predictor for distinguishing patients with PD from those with non-PD in all patients with gastrointestinal cancer, with a sensitivity of 75.0% and a specificity of 93.9%.
CONCLUSION
The gut microbiome of patients with esophageal cancer, gastric cancer, and colorectal cancer differs from those of healthy people. The abundance alteration of in patients with GI cancer might be a predictor of chemotherapy efficacy.
PubMed: 35004303
DOI: 10.3389/fonc.2021.781697 -
FEMS Microbiology Ecology Jun 2010The bioactivity of lignans depends on their transformation by gut bacteria. The intestinal bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and...
The bioactivity of lignans depends on their transformation by gut bacteria. The intestinal bacteria Clostridium saccharogumia, Eggerthella lenta, Blautia producta and Lactonifactor longoviformis convert the plant lignan secoisolariciresinol diglucoside via secoisolariciresinol (SECO) into the bioactive enterolignans enterodiol (ED) and enterolactone (EL). While the in vitro conversion of lignans by these bacteria has already been demonstrated, it is unclear whether this defined community is also capable of catalysing lignan transformation in vivo. We therefore associated germ-free rats with these four species. Germ-free rats served as a control. All animals were fed a diet containing 5% ground flaxseed. The caecal contents of rats associated with the four lignan-activating bacteria (ALB rats) contained SECO, ED and EL. The maximal EL formation rate from lignans in the pooled caecal contents of ALB rats was 7.52 nmol min(-1) g(-1) dry matter. The ALB rats excreted EL, but no SECO and ED, in their urine. The caecal contents of germ-free rats contained SECO, but no ED and EL. Their urine was devoid of lignans. Hence, the presence of enterolignans in the ALB rats, but not in the germ-free rats, demonstrates that this defined microbial community is capable of transforming plant lignans into EL in vivo.
Topics: 4-Butyrolactone; Animals; Biotransformation; Butylene Glycols; Cecum; Diet; Feces; Flax; Germ-Free Life; Gram-Positive Bacteria; Lignans; Rats; Rats, Sprague-Dawley
PubMed: 20370826
DOI: 10.1111/j.1574-6941.2010.00863.x -
Metabolites Apr 2023Diet energy is a key component of pet food, but it is usually ignored during pet food development and pet owners also have limited knowledge of its importance. This...
Diet energy is a key component of pet food, but it is usually ignored during pet food development and pet owners also have limited knowledge of its importance. This study aimed to explore the effect of diet energy on the body condition, glucolipid metabolism, fecal microbiota and metabolites of adult beagles and analyze the relation between diet and host and gut microbiota. Eighteen healthy adult neutered male beagles were selected and randomly divided into three groups. Diets were formulated with three metabolizable energy (ME) levels: the low-energy (Le) group consumed a diet of 13.88 MJ/kg ME; the medium-energy (Me) group consumed a diet of 15.04 MJ/kg ME; and the high-energy (He) group consumed a diet of 17.05 MJ/kg ME. Moreover, the protein content of all these three diets was 29%. The experiment lasted 10 weeks, with a two-week acclimation period and an eight-week test phase. Body weight, body condition score (BCS), muscle condition score (MCS) and body fat index (BFI) decreased in the Le group, and the changes in these factors in the Le group were significantly higher than in the other groups ( < 0.05). The serum glucose and lipid levels of the Le and He groups changed over time ( < 0.05), but those of the Me group were stable ( > 0.05). The fecal pH of the Le and He groups decreased at the end of the trial ( < 0.05) and we found that the profiles of short-chain fatty acids (SCFAs) and bile acids (BAs) changed greatly, especially secondary BAs ( < 0.05). As SCFAs and secondary BAs are metabolites of the gut microbiota, the fecal microbiota was also measured. Fecal 16S rRNA gene sequencing found that the Me group had higher α-diversity indices ( < 0.05). The Me group had notably higher levels of gut probiotics, such as , and ( < 0.05). The diet-host-fecal microbiota interactions were determined by network analysis, and fecal metabolites may help to determine the best physical condition of dogs, assisting pet food development. Overall, feeding dogs low- or high-energy diets was harmful for glucostasis and promoted the relative abundance of pathogenic bacteria in the gut, while a medium-energy diet maintained an ideal body condition. We concluded that dogs that are fed a low-energy diet for an extended period may become lean and lose muscle mass, but diets with low energy levels and 29% protein may not supply enough protein for dogs losing weight.
PubMed: 37110212
DOI: 10.3390/metabo13040554 -
Frontiers in Cellular and Infection... 2022Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified...
RATIONALE AND OBJECTIVE
Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota.
STUDY DESIGN
This was a cross-sectional cohort study.
SETTINGS AND PARTICIPANTS
Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients.
RESULTS
Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients was , and at the species level hemodialysis patients showed significant abundance in , , and peritoneal dialysis patients showed higher abundance in (p ≤ 0.05) than the control group. Pathways pertaining to the production of uremic toxins were enriched in CKD patients. The abundance of the bacterial species depended on the type of dialysis treatment.
CONCLUSION
This study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients' condition.
Topics: Bacteria; Bacteroides; Cross-Sectional Studies; Dysbiosis; Female; Gastrointestinal Microbiome; Humans; Male; Microbiota; RNA, Ribosomal, 16S; Renal Insufficiency, Chronic; Taiwan; Toxins, Biological; Uremic Toxins
PubMed: 35558102
DOI: 10.3389/fcimb.2022.726256 -
Research Square Apr 2024Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood. Here, we demonstrate in Malian...
Malaria is a major public health problem, but many of the factors underlying the pathogenesis of this disease are not well understood. Here, we demonstrate in Malian children that susceptibility to febrile malaria following infection with is associated with the composition of the gut microbiome prior to the malaria season. Gnotobiotic mice colonized with the fecal samples of malaria-susceptible children had a significantly higher parasite burden following infection compared to gnotobiotic mice colonized with the fecal samples of malaria-resistant children. The fecal microbiome of the susceptible children was enriched for bacteria associated with inflammation, mucin degradation, gut permeability and inflammatory bowel disorders (e.g., and sp. YL32). However, the susceptible children also had a greater abundance of bacteria known to produce anti-inflammatory short-chain fatty acids and those associated with favorable prognosis and remission following dysbiotic intestinal events (e.g., and . Metabolomics analysis of the human fecal samples corroborated the existence of inflammatory and recovery-associated features within the gut microbiome of the susceptible children. There was an enrichment of nitric oxide-derived DNA adducts (deoxyinosine and deoxyuridine) and long-chain fatty acids, the absorption of which has been shown to be inhibited by inflamed intestinal epithelial cells, and a decrease in the abundance of mucus phospholipids. Nevertheless, there were also increased levels of pseudouridine and hypoxanthine, which have been shown to be regulated in response to cellular stress and to promote recovery following injury or hypoxia. Overall, these results indicate that the gut microbiome may contribute malaria pathogenesis and suggest that therapies targeting intestinal inflammation could decrease malaria susceptibility.
PubMed: 38645126
DOI: 10.21203/rs.3.rs-3974068/v1 -
Gut Microbes May 2020The formation of secondary bile acids by gut microbes is a current topic of considerable biomedical interest. However, a detailed understanding of the biology of...
The ' lifestyle' of bile acid 7α-dehydroxylating bacteria: comparative genomics, metatranscriptomic, and bile acid metabolomics analysis of a defined microbial community in gnotobiotic mice.
The formation of secondary bile acids by gut microbes is a current topic of considerable biomedical interest. However, a detailed understanding of the biology of anaerobic bacteria in the genus that are capable of generating secondary bile acids is lacking. We therefore sought to determine the transcriptional responses of two prominent secondary bile acid producing bacteria, and to bile salts () and the cecal environment of gnotobiotic mice. The genomes of DSM 15053 and DSM 13275 were closed, and found to encode 3,647 genes (3,584 protein-coding) and 2,363 predicted genes (of which 2,239 are protein-coding), respectively, and 1,035 orthologs were shared between and . RNA-Seq analysis was performed in growth medium alone, and in the presence of cholic acid (CA) and deoxycholic acid (DCA). Growth with CA resulted in differential expression (>0.58 logFC; FDR < 0.05) of 197 genes in and 118 genes in . The bile acid-inducible operons () from each organism were highly upregulated in the presence of CA but not DCA. We then colonized germ-free mice with human gut bacterial isolates capable of metabolizing taurine-conjugated bile acids. This consortium included bile salt hydrolase-expressing ATCC 8492, ATCC 8482, DSM 20701, as well as taurine-respiring DSM 11045, and deoxycholic/lithocholic acid generating DSM 15053 and DSM 13275. Butyrate and iso-bile acid-forming ATCC 27340 was also included. The Bacteroidetes made up 84.71% of 16S rDNA cecal reads, , constituted 14.7%, and the clostridia made up <.75% of 16S rDNA cecal reads. Bile acid metabolomics of the cecum, serum, and liver indicate that the synthetic community were capable of functional bile salt deconjugation, oxidation/isomerization, and 7α-dehydroxylation of bile acids. Cecal metatranscriptome analysis revealed expression of genes involved in metabolism of taurine-conjugated bile acids. The transcriptomes of and suggest fermentation of simple sugars and utilization of amino acids glycine and proline as electron acceptors. Genes predicted to be involved in trimethylamine (TMA) formation were also expressed.
Topics: Animals; Bacteria, Anaerobic; Bacteroides; Bile Acids and Salts; Bilophila; Cecum; Cholic Acids; Clostridium; Gene Expression Regulation, Bacterial; Genome, Bacterial; Genomics; Germ-Free Life; Humans; Metabolome; Mice; Mice, Inbred C57BL; Microbiota; Operon; RNA-Seq; Transcriptome; Up-Regulation
PubMed: 31177942
DOI: 10.1080/19490976.2019.1618173 -
Microorganisms Sep 2020Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still...
Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to and , inherited by respective donors. Moreover, a decrease of and , and the increment of , , , , , and were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.
PubMed: 32992653
DOI: 10.3390/microorganisms8101486 -
Gut Microbes 2021. Our recent publication (Chey et al., Nutrients 2020) showed that a 30-day administration of pure galacto-oligosaccharides (GOS) significantly reduced symptoms and... (Randomized Controlled Trial)
Randomized Controlled Trial
A double-blind, 377-subject randomized study identifies , and as long-term potential key players in the modulation of the gut microbiome of lactose intolerant individuals by galacto-oligosaccharides.
. Our recent publication (Chey et al., Nutrients 2020) showed that a 30-day administration of pure galacto-oligosaccharides (GOS) significantly reduced symptoms and altered the fecal microbiome in patients with lactose intolerance (LI). . In this addendum, we performed an in-depth analysis of the fecal microbiome of the 377 LI patients randomized to one of two GOS doses (Low, 10-15 grams/day or High, 15-20 grams/day), or placebo in a multi-center, double-blinded, placebo-controlled trial. Sequencing of 16S rRNA amplicons was done on GOS or placebo groups at weeks zero (baseline), four (end of treatment), nine, 16 and 22. Taxa impacted by treatment and subsequent dairy consumption included lactose-fermenting species of , and . Increased secondary fermentation microorganisms included and species, , and . Finally, tertiary fermenters that use acetate to generate butyrate were also increased, including , and . . Results confirmed and expanded data on GOS microbiome modulation in LI individuals. Microbiome analysis at 16 and 22 weeks after treatment further suggested relatively long-term benefits when individuals continued consumption of dairy products.
Topics: Actinobacteria; Clostridiales; Double-Blind Method; Gastrointestinal Microbiome; Humans; Lactobacillus; Lactose Intolerance; Oligosaccharides; Placebos; Prebiotics; RNA, Ribosomal, 16S
PubMed: 34365905
DOI: 10.1080/19490976.2021.1957536