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Cancers Apr 2024The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies...
The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder ( = 28) and non-responder ( = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of and was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.
PubMed: 38730627
DOI: 10.3390/cancers16091675 -
Gut Microbes 2024Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify...
Ulcerative colitis (UC) is a challenging form of inflammatory bowel disease, and its etiology is intricately linked to disturbances in the gut microbiome. To identify the potential alleviators of UC, we employed an integrative analysis combining microbial community modeling with advanced machine learning techniques. Using metagenomics data sourced from the Integrated Human Microbiome Project, we constructed individualized microbiome community models for each participant. Our analysis highlighted a significant decline in both α and β-diversity of strain-level microbial populations in UC subjects compared to controls. Distinct differences were also observed in the predicted fecal metabolite profiles and strain-to-metabolite contributions between the two groups. Using tree-based machine learning models, we successfully identified specific microbial strains and their associated metabolites as potential alleviators of UC. Notably, our experimental validation using a dextran sulfate sodium-induced UC mouse model demonstrated that the administration of ATCC 43,184 and N-acetyl-D-mannosamine provided notable relief from colitis symptoms. In summary, our study underscores the potential of an integrative approach to identify novel therapeutic avenues for UC, paving the way for future targeted interventions.
Topics: Animals; Mice; Humans; Colitis, Ulcerative; Gastrointestinal Microbiome; Inflammatory Bowel Diseases; Colitis; Machine Learning
PubMed: 38563656
DOI: 10.1080/19490976.2024.2336877 -
Microbiological Research Jun 2024As the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various...
As the most abundant gram-negative bacterial order in the gastrointestinal tract, Bacteroidales bacteria have been extensively studied for their contribution to various aspects of gut health. These bacteria are renowned for their involvement in immunomodulation and their remarkable capacity to break down complex carbohydrates and fibers. However, the human gut microbiota is known to produce many metabolites that ultimately mediate important microbe-host and microbe-microbe interactions. To gain further insights into the metabolites produced by the gut commensal strains of this order, we examined the metabolite composition of their bacterial cell cultures in the stationary phase. Based on their abundance in the gastrointestinal tract and their relevance in health and disease, we selected a total of six bacterial strains from the relevant genera Bacteroides, Phocaeicola, Parabacteroides, and Segatella. We grew these strains in modified Gifu anaerobic medium (mGAM) supplemented with mucin, which resembles the gut microbiota's natural environment. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolite profiling revealed 179 annotated metabolites that had significantly differential abundances between the studied bacterial strains and the control growth medium. Most of them belonged to classes such as amino acids and derivatives, organic acids, and nucleot(s)ides. Of particular interest, Segatella copri DSM 18205 (previously referred to as Prevotella copri) produced substantial quantities of the bioactive metabolites phenylethylamine, tyramine, tryptamine, and ornithine. Parabacteroides merdae CL03T12C32 stood out due to its ability to produce cadaverine, histamine, acetylputrescine, and deoxycarnitine. In addition, we found that strains of the genera Bacteroides, Phocaeicola, and Parabacteroides accumulated considerable amounts of proline-hydroxyproline, a collagen-derived bioactive dipeptide. Collectively, these findings offer a more detailed comprehension of the metabolic potential of these Bacteroidales strains, contributing to a better understanding of their role within the human gut microbiome in health and disease.
Topics: Humans; Chromatography, Liquid; Liquid Chromatography-Mass Spectrometry; Tandem Mass Spectrometry; Bacteria; Gastrointestinal Microbiome
PubMed: 38518452
DOI: 10.1016/j.micres.2024.127700 -
Cancers Oct 2023Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in...
Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with and were elevated in mucosa from polyp patients, while ASVs associated with , , and were relatively decreased. Only was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.
PubMed: 37894412
DOI: 10.3390/cancers15205045 -
Frontiers in Nutrition 2023The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren.
UNLABELLED
The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren.
METHODS
Male (114) and female children (8-10 years) belonging to five primary schools in the neighborhoods of Turin were classified as active (A) or sedentary (S) based on PAQ-C-It questionnaire. PCR amplification of salivary DNA targeted the hypervariable V3-V4 regions of the 16S rRNA bacterial genes. DADA2 workflow was used to infer the Amplicon Sequence Variants and the taxonomic assignments; the beta-diversity was obtained by PCoA with the UniFrac method; LEfSe algorithm, threshold at 5%, and Log LDA cutoff at ±0.5 were used to identify differently abundant species in A compared to S saliva sample. Daily food intake was assessed by 3-Days food record. The metabolic potential of microbial communities was assessed by PICRUSt.
RESULTS
No significant differences were found in individual's gender distribution ( = 0.411), anthropometry, BMI ( > 0.05), and all diet composition between A and S groups ( > 0.05). Eight species were differently abundant: (LDA score = -3.76; FDR = 1.5×10-03), (LDA score = -3.17; FDR = 7.45×10-03), (LDA score = -2.96; FDR = 2.76×10-05), (LDA score = -2.43; FDR = 1.3×10-02) are enriched in the A group; , (LDA score = -3.9; FDR = 5.27×10-04), (LDA score = 4.23; FDR = 1.93×10-02), (LDA score = 4.43; FDR = 1.31×10-02; LDA score = 2.94; FDR = 7.45×10-03) are enriched in the S group. A prevalence of superpathway of fatty acid biosynthesis initiation () and catechol degradation II (meta-cleavage pathway) was found in saliva from A compared to S children.
CONCLUSION
Our results showed that active children had an enrichment of species and genera mainly associated with a healthier profile. By contrast, the genera and the species enriched in the sedentary group could be linked to human diseases.
PubMed: 37671197
DOI: 10.3389/fnut.2023.1226891 -
Gut Microbes 2023The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and...
The gut microbiota is involved in the production of numerous metabolites that maintain host wellbeing. The assembly of the gut microbiome is highly dynamic, and influenced by many postnatal factors, moreover, little is known about the development of the gut metabolome. We showed that geography has an important influence on the microbiome dynamics in the first year of life based on two independent cohorts from China and Sweden. Major compositional differences since birth were the high relative abundance of in the Swedish cohort and in the Chinese cohort. We analyzed the development of the fecal metabolome in the first year of life in the Chinese cohort. Lipid metabolism, especially acylcarnitines and bile acids, was the most abundant metabolic pathway in the newborn gut. Delivery mode and feeding induced particular differences in the gut metabolome since birth. In contrast to C-section newborns, medium- and long-chain acylcarnitines were abundant at newborn age only in vaginally delivered infants, associated by the presence of bacteria such as and . Our data provide a basis for understanding the maturation of the fecal metabolome and the metabolic role of gut microbiota in infancy.
Topics: Gastrointestinal Microbiome; Humans; Infant, Newborn; Infant; China; Bile Acids and Salts; Amino Acids; Sweden; Bacteroides; Streptococcus; Feces; Lipid Metabolism; Feeding Behavior; Metabolic Networks and Pathways; Delivery, Obstetric; Female; Pregnancy; Cesarean Section; Longitudinal Studies; Male
PubMed: 37424334
DOI: 10.1080/19490976.2023.2231596 -
Immunity Feb 2023The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations...
The physiological and immune changes that occur during pregnancy are associated with worsened disease outcomes during infection and sepsis. How these perturbations exacerbate inflammation has not been explored. Here, using antibiotic treatment and fecal microbial transfers, we showed that sepsis susceptibility is driven by pregnancy-induced changes to gut microbiome in mice and humans. Integrative multiomics and genetically engineered bacteria revealed that reduced Parabacteroides merdae (P. merdae) abundance during pregnancy led to decreased formononetin (FMN) and increased macrophage death. Mechanistically, FMN inhibited macrophage pyroptosis by suppressing nuclear accumulation of hnRNPUL2 and subsequent binding to the Nlrp3 promoter. Treatment with FMN or deletion of murine hnRNPUL2 protected against septic inflammation. Intestinal abundances of P. merdae and FMN inversely correlated with the progression of septic patients. Our data reveal a microbe-immune axis that is disrupted in pregnant septic hosts, highlighting the potential of the FMN-hnRNPUL2-NLRP3 axis in providing promising therapeutic strategies for sepsis.
Topics: Pregnancy; Female; Humans; Animals; Mice; Gastrointestinal Microbiome; Pyroptosis; NLR Family, Pyrin Domain-Containing 3 Protein; Macrophages; Sepsis; Inflammation
PubMed: 36792573
DOI: 10.1016/j.immuni.2023.01.015 -
MSystems Feb 2023Previous study found that appropriate high-fiber diet (containing 19.10% total dietary fiber [TDF], treatment II) did not reduce apparent fiber digestibility of Chinese...
Previous study found that appropriate high-fiber diet (containing 19.10% total dietary fiber [TDF], treatment II) did not reduce apparent fiber digestibility of Chinese Suhuai finishing pigs and increased the yield of short-chain fatty acids (SCFAs), but too high-fiber diet (containing 24.11% TDF, treatment IV) significantly reduced apparent fiber digestibility compared with normal diet (containing 16.70% TDF, control group). However, characteristics of microbiota at the species level and histological structure in pigs with the ability to digest appropriate high-fiber diets were still unknown. This study conducted comparative analysis of cecal physiology and microbial populations colonizing cecal mucosa. The results showed intestinal development indexes including cecum length, densities of cecal goblet cells, and renewal of cecal epithelial cells in treatment II and IV had better performance than those in the control. Paludibacter jiangxiensis, Coprobacter fastidiosus, Bacteroides coprocola CAG:162, Bacteroides barnesiae, and Parabacteroides merdae enriched in treatment II expressed large number of glycoside hydrolase (GH)-encoding genes and had the largest number of GH families. In addition, pathogenic bacteria (Shigella sonnei, Mannheimia haemolytica, and Helicobacter felis) were enriched in treatment IV. Correlation analysis revealed that the intestinal development index positively correlated with the relative abundance of cecal mucosal microbiota and the amount of digested fiber. These results indicated that increased proportions of fiber-degrading microbes and enhanced intestinal development jointly promote the host to digest an appropriate high-fiber diet. However, although too-high fiber levels in diet could maintain the adaptive development of cecal epithelium, the proportions of pathogenic bacteria increased, which might lead to a decrease of fiber digestion in pigs. Although studies about the effects of dietary fiber on fiber digestion and intestinal microbiota of pigs were widely in progress, few studies have been conducted on the dynamic response of intestinal microbiota to dietary fiber levels, and the characteristics of intestinal microbiota and intestinal epithelial development adapted to high-fiber diet s were still unclear. Appropriate high fiber promoted the thickness of large intestine wall, increased the density of cecal goblet cells, and promoted the renewal of cecal epithelial cells. In addition, appropriate high fiber improves the microbial abundance with fiber-digesting potential. However, excessive dietary fiber caused an increase in the abundance of pathogenic bacteria. These results indicated that an increased proportion of fiber-degrading microbes and enhanced intestinal development jointly promote host to digest appropriate high-fiber diets. However, although too-high fiber levels in diet could maintain the adaptive development of cecal epithelium, the proportions of pathogenic bacteria increased, which might lead to a decrease of fiber digestion in pigs. Our data provided a theoretical basis for rational and efficient utilization of unconventional feed resources in pig production.
Topics: Swine; Animals; Digestion; Cecum; Diet; Dietary Fiber; Intestinal Mucosa
PubMed: 36511688
DOI: 10.1128/msystems.00937-22 -
PloS One 2022Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity....
Time series strain tracking analysis post fecal transplantation identifies individual specific patterns of fecal dominant donor, recipient, and unrelated microbial strains.
BACKGROUND
Fecal microbial transplantation (FMT) has been used with the therapeutic intent to change the functions of the gut microbial community in metabolism and host immunity. For most of these therapies, the recipients are not given antibiotics to eliminate the microbial community prior to transplant with donor fecal microbes resulting in the initial gut microbial community following FMT consisting of a consortium of donor and recipient microbes. The detailed analysis of the fecal samples from these FMT over time provides a unique opportunity to study the changes in the gut microbial strain community that occurs following the introduction of new microbial strains (donor) into an established community (recipient).
METHODS
In this study, we have metagenomic data set consisting of 5 FMT that contained donor, recipient and recipient post FMT taken multiple times for periods up to 535 days after the FMT. We used two established strain tracking methods, Window-based Single Nucleotide Variant (SNV) Similarity (WSS) and StrainPhlAn, to determine the presence of donor and recipient microbial strains following FMT. To assess recombination between donor and recipient strains of Bacteroides vulgatus post FMT, we used BLAST+ to analyze the data sets for Bacteroidales-specific antimicrobial proteins (BSAP-3) that have known functions to restrict species specific replication.
RESULTS
We found that Alistipes onderdonkii, Alistipes shahii, Alistipes putredinis, and Parabacteroides merdae, all had patterns post FMT consisting of either dominant donor or recipient microbial strains in the feces. In contrast, the analysis of Bacteroides spp. in five FMT pairs revealed inter-individual oscillation over time with the appearance of either donor or recipient fecal strain dominance. In some instances, B. vulgatus and B. uniformis were also identified after FMT that were not related to either the donor or recipient. Finally, in one of the FMT, we identified a distinct B. vulgatus strain post-FMT that matched the pre-FMT strain but was BSAP-3 positive, suggesting a possible recombination event between the donor and recipient strains.
CONCLUSION
The complex oscillating patterns of the appearance of fecal dominant donor, recipient or unrelated strains following extended times post FMT provide new insights into the dynamics of the microbial community interactions with the recipients following FMT. The result from our analysis has implications for the use of FMT to predictably change the biological functions of the gut community in metabolism and host immunity.
Topics: Anti-Bacterial Agents; Fecal Microbiota Transplantation; Feces; Nucleotides; Time Factors
PubMed: 36107983
DOI: 10.1371/journal.pone.0274633 -
Frontiers in Cellular and Infection... 2022Aging is now the most profound risk factor for almost all non-communicable diseases. Studies have shown that probiotics play a specific role in fighting aging. We used...
Aging is now the most profound risk factor for almost all non-communicable diseases. Studies have shown that probiotics play a specific role in fighting aging. We used metagenomic sequencing to study the changes in gut microbes in different age groups and found that aging had the most significant effect on subjects' gut microbe structure. Our study divided the subjects (n=614) into two groups by using 50 years as the age cut-off point for the grouping. Compared with the younger group, several species with altered abundance and specific functional pathways were found in the older group. At the species level, the abundance of , , , , , and were increased in older individuals. They were positively correlated to the pathways responsible for lipopolysaccharide (LPS) biosynthesis and the degradation of short-chain fatty acids (SCFAs). On the contrary, the levels of , , and were decreased in the older group, which negatively correlated with the above pathways (p-value<0.05). Functional prediction revealed 92 metabolic pathways enriched in the older group significantly higher than those in the younger group (p-value<0.05), especially pathways related to LPS biosynthesis and the degradation of SCFAs. Additionally, we established a simple non-invasive model of aging, nine species (, , , , , , , , and ) were selected to construct the model. The area under the receiver operating curve (AUC) of the model implied that supplemented probiotics might influence aging. We discuss the features of the aging microbiota that make it more amenable to pre-and probiotic interventions. We speculate these metabolic pathways of gut microbiota can be associated with the immune status and inflammation of older adults. Health interventions that promote a diverse microbiome could influence the health of older adults.
Topics: Aged; Bacteroides; Bacteroides fragilis; Bacteroidetes; Bifidobacterium longum; Clostridiales; Escherichia coli; Feces; Firmicutes; Gastrointestinal Microbiome; Humans; Lipopolysaccharides
PubMed: 35959379
DOI: 10.3389/fcimb.2022.877914