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Chinese Medicine Oct 2022As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that...
BACKGROUND
As a first-line chemotherapeutic agent, 5-fluorouracil (5-FU) exhibits many side effects, weakening its efficacy in cancer treatment. In this study, we hypothesize that Poria cocos polysaccharides (PCP), a traditional Chinese herbal medicine with various bioactivities and prebiotic effects, might improve the therapeutic effect of 5-FU by restoring the homeostasis of the gut microenvironment and the commensal gut microflora.
METHODS
Apc mice were employed to evaluate the anti-cancer effect of 5-FU in conjunction with PCP treatment. Body weight and food consumption were monitored weekly. Polyp count was used to assess the anti-cancer effect of PCP and 5-FU. Expressions of mucosal cytokines and gut epithelial junction molecules were measured using qRT-PCR. 16S rRNA gene sequencing of fecal DNAs was used to evaluate the compositional changes of gut microbiota (GM). Transplantation of Lactobacillus johnsonii and Bifidobacterium animalis were performed to verify the prebiotic effects of PCP in improving the efficacy of 5-FU.
RESULTS
The results showed that PCP treatment alleviated the weight loss caused by 5-FU treatment and reduced the polyp burden in Apc mice. Additionally, PCP treatment eased the cytotoxic effects of 5-FU by reducing the expressions of pro-inflammatory cytokines, increasing the anti-inflammatory cytokines; and significantly improving the gut barriers by enhancing the tight junction proteins and associated adhesion molecules. Furthermore, 16S rRNA gene sequencing data showed that PCP alone or with 5-FU could stimulate the growth of probiotic bacteria (Bacteroides acidifaciens, Bacteroides intestinihominis, Butyricicoccus pullicaecorum, and the genera Lactobacillus, Bifidobacterium, Eubacterium). At the same time, it inhibited the growth of potential pathogens (e.g., Alistipes finegoldii, Alistipes massiliensis, Alistipes putredinis., Citrobacter spp., Desulfovibrio spp., and Desulfovibrio desulfuricans). Moreover, the results showed that transplantation of L.johnsonii and B.animalis effectively reduced the polyp burden in Apc mice being treated with 5-FU.
CONCLUSION
Our study showed that PCP could effectively improve the anti-cancer effect of 5-FU by attenuating its side effects, modulating intestinal inflammation, improving the gut epithelial barrier, and modulating the gut microbiota of Apc mice.
PubMed: 36192796
DOI: 10.1186/s13020-022-00667-8 -
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 Molecular Biosciences 2022IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and...
IgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia. Its pathogenesis involves higher expression of galactose-deficient IgA1 (Gd-IgA1) and dysregulated intestinal mucosal immunity. The objective of this study was to explore whether specific gut microbiota and associated enzymes affect Gd-IgA1 in IgAN. This study carried out shotgun metagenomic sequencing with Illumina on fecal samples collected from 20 IgAN patients (IgAN group) and 20 healthy controls (HCs group) who were recruited from January 2016 to December 2018 at the Second Clinical College of Guangzhou University of Chinese Medicine. Differences analysis in gut microbiota was performed to determine the overall microbiota composition, the representative enterotypes, and the microbiota abundance. Correlations between gut microbiota and clinical indicators were assessed by Spearman's analysis. Moreover, the functional prediction of microbial communities and the quantitative calculation of enzymes encoded by microbiome were performed using the MetaCyc pathway and the bioBakery three platform, respectively. and levels were higher, while and levels were lower in the IgAN group compared to HCs group. Enterotype I characterized by was closely related to the IgAN patients. Moreover, , and were characteristic bacteria enriched in IgAN patients. Spearman's correlation analysis found that and were positively correlated with urine protein-creatinine ratio, while showed a direct association with red blood cells in urine, and and were positively correlated with eGFR. These results indicated that intestinal dysbacteriosis occurred in IgAN patients and was associated with clinical and biochemical features. In addition, MetaCyc pathway analysis predicted microbiota-related metabolic pathways, including the biosynthesis of amino acids and glycans, were associated with the IgAN group. Microbial enzymes analysis highlighted that Gd-IgA1-associated α-galactosidase and α-N-acetyl-galactosaminidase secreted by were enriched in IgAN patients. These findings suggested that α-galactosidase and α-N-acetyl-galactosaminidase secreted by might be related to the production of Gd-IgA1, indicating that enzymes originated from abnormal intestinal microbiota may contribute to the production of Gd-IgA1 and play an important role in the pathogenesis of IgAN.
PubMed: 36090029
DOI: 10.3389/fmolb.2022.970723 -
Nutrients Aug 2022Recent research advances examining the gut microbiome and its association with human health have indicated that microbiota-targeted intervention is a promising means for... (Randomized Controlled Trial)
Randomized Controlled Trial
Recent research advances examining the gut microbiome and its association with human health have indicated that microbiota-targeted intervention is a promising means for health modulation. In this study, elderly people in long-term care (aged 83.2 ± 5.3 year) with malnutrition (MNA-SF score ≤ 7) were recruited in a community hospital for a 12-week randomized, single-blind clinical trial with Clostridium butyricum. Compared with the basal fluctuations of the control group, an altered gut microbiome was observed in the intervention group, with increased (p < 0.05) Coprobacillus species, Carnobacterium divergens, and Corynebacterium_massiliense, and the promoted growth of the beneficial organisms Akketmanse muciniphila and Alistipes putredinis. A concentrated profile of 14 increased Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs (KOs) that were enriched in cofactor/vitamin production and carbohydrate metabolism pathways were discovered; the genes were found to be correlated (p < 0.05) with an elevated abundance of plasma metabolites and short-chain fatty acids (SCFAs), unsaturated medium- to long-chain fatty acids (MFA, LFA), carnitines, and amino acids, thus suggesting a coordinated ameliorated metabolism. Proinflammatory factor interferon-gamma (IFN-γ) levels decreased (p < 0.05) throughout the intervention, while the gut barrier tight junction protein, occludin, rose in abundance (p = 0.059), and the sensitive nutrition biomarker prealbumin improved, in contrast to the opposite changes in control. Based on our results obtained during a relatively short intervention time, C. butyricum might have great potential for improving nutrition and immunity in elderly people in long-term care with malnutrition through the alteration of gut microbiota, increasing the abundance of beneficial bacteria and activating the metabolism in SCFA and cofactor/vitamin production, bile acid metabolism, along with efficient energy generation.
Topics: Aged; Clostridium butyricum; Fatty Acids, Volatile; Humans; Long-Term Care; Malnutrition; Microbiota; Single-Blind Method; Vitamins
PubMed: 36079806
DOI: 10.3390/nu14173546 -
Cancer Medicine Feb 2023Colorectal cancer (CRC) incidence is increasing in young patients without a clear etiology. Emerging data have implicated the fecal microbiome in CRC carcinogenesis.... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Colorectal cancer (CRC) incidence is increasing in young patients without a clear etiology. Emerging data have implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC is poorly defined.
METHODS
We performed a meta-analysis of fecal metagenomics sequencing data from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate features of the fecal metagenome associated with CRC. We hypothesized that known carcinogenic virulence factors (colibactin, fadA) and species abundance may be differentially enriched in young CRC patients relative to older CRC patients and controls.
RESULTS
Summary odds ratios (OR) for CRC were increased with the presence of colibactin (OR 1.92 95% CI 1.08-3.38), fadA (OR 4.57 95% CI 1.63-12.85), and F. nucleatum (OR 6.93 95% CI 3.01-15.96) in meta-analysis models adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of Fusobacterium nucleatum (OR = 1.40 [1.18; 1.65]) and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. Species relative abundance was differentially enriched in young CRC patients for five species-Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis.
CONCLUSION
In this study, we observed strong associations with CRC status for colibactin, fadA, and Fusobacterium nucleatum with CRC relative to controls. In addition, we identified several microbial species differentially enriched in young colorectal cancer patients. Studies targeting the young CRC patients are warranted to elucidate underlying preclinical mechanisms.
Topics: Humans; Colorectal Neoplasms; Metagenome; Metagenomics; Fusobacterium nucleatum; Carcinogenesis; Microbiota
PubMed: 36056757
DOI: 10.1002/cam4.5197 -
Brain, Behavior, and Immunity Nov 2022Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and...
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by deficits in social behaviour, increased repetitive behaviour, anxiety and gastrointestinal symptoms. The aetiology of ASD is complex and involves an interplay of genetic and environmental factors. Emerging pre-clinical and clinical studies have documented a potential role for the gut microbiome in ASD, and consequently, the microbiota represents a potential target in the development of novel therapeutics for this neurodevelopmental disorder. In this study, we investigate the efficacy of the live biotherapeutic strain, Blautia stercoris MRx0006, in attenuating some of the behavioural deficits in the autism-relevant, genetic mouse model, BTBR T+ Itpr3tf/J (BTBR). We demonstrate that daily oral administration with MRx0006 attenuates social deficits while also decreasing repetitive and anxiety-like behaviour. MRx0006 administration increases the gene expression of oxytocin and its receptor in hypothalamic cells in vitro and increases the expression of hypothalamic arginine vasopressin and oxytocin mRNA in BTBR mice. Additionally at the microbiome level, we observed that MRx0006 administration decreases the abundance of Alistipes putredinis, and modulates the faecal microbial metabolite profile. This alteration in the metabolite profile possibly underlies the observed increase in expression of oxytocin, arginine vasopressin and its receptors, and the consequent improvements in behavioural outcomes. Taken together, these findings suggest that the live biotherapeutic MRx0006 may represent a viable and efficacious treatment option for the management of physiological and behavioural deficits associated with ASD.
Topics: Animals; Anxiety; Arginine Vasopressin; Autism Spectrum Disorder; Autistic Disorder; Clostridiales; Disease Models, Animal; Mice; Mice, Inbred Strains; Oxytocin; RNA, Messenger
PubMed: 35995237
DOI: 10.1016/j.bbi.2022.08.007 -
Frontiers in Cellular and Infection... 2022It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is...
It is predicted that by 2035, metabolic syndrome (MS) will be found in nearly more than half of our adult population, seriously affecting the health of our body. MS is usually accompanied by the occurrence of abnormal liver enzymes, such as elevated gamma-glutamyl transpeptidase (GGT). More and more studies have shown that the gut microbiota is involved in MS; however, the correlation between gut microbiota and MS with elevated GGT has not been studied comprehensively. Especially, there are few reports about its role in the physical examination of the population of men with MS and elevated GGT. By using the whole-genome shotgun sequencing technology, we conducted a genome-wide association study of the gut microbiome in 66 participants diagnosed as having MS accompanied by high levels of GGT (case group) and 66 participants with only MS and normal GGT level (control group). We found that the number of gut microbial species was reduced in participants in the case group compared to that of the control group. The overall microbial composition between the two groups is of significant difference. The gut microbiota in the case group is characterized by increased levels of "harmful bacteria" such as , , unclassified, , and and decreased levels of "beneficial bacteria" such as , , , , , and . Moreover, the pathways of POLYAMSYN-PWY, ARG+POLYAMINE-SYN, PWY-6305, and GOLPDLCAT-PWY were also increased in the case group, which may play a role in the elevation of GGT by producing amine, polyamine, putrescine, and endogenous alcohol. Taken together, there are apparent changes in the composition of the gut microbiome in men with MS and abnormal GGT levels, and it is high time to discover specific gut microbiome as a potential therapeutic target in that population. More in-depth studies of relevant mechanism could offer some new methods for the treatment of MS with elevated GGT.
Topics: Adult; Gastrointestinal Microbiome; Genome-Wide Association Study; Humans; Male; Metabolic Syndrome; Polyamines; gamma-Glutamyltransferase
PubMed: 35967853
DOI: 10.3389/fcimb.2022.946757 -
Frontiers in Microbiology 2022The host and its symbiotic bacteria form a biological entity, holobiont, in which they share a dynamic connection characterized by symbiosis, co-metabolism, and...
The host and its symbiotic bacteria form a biological entity, holobiont, in which they share a dynamic connection characterized by symbiosis, co-metabolism, and coevolution. However, how these collaborative relationships were maintained over evolutionary time remains unclear. In this research, the small non-coding RNA (sncRNA) profiles of cecum and their bacteria contents were measured from lines of chickens that have undergone long-term selection for high (HWS) or low (LWS) 56-day body weight. The results from these lines that originated from a common founder population and maintained under the same husbandry showed an association between host intestinal sncRNA expression profile (miRNA, lncRNA fragment, mRNA fragment, snoRNA, and snRNA) and intestinal microbiota. Correlation analyses suggested that some central miRNAs and mRNA fragments had interactions with the abundance of intestinal microbial species and microbiota functions. miR-6622-3p, a significantly differentially expressed (DE) miRNA was correlated with a body weight gain related bacterium, s. Our results showed that host sncRNAs may be mediators of interaction between the host and its intestinal microbiome. This provides additional clue for holobiont concepts.
PubMed: 35847106
DOI: 10.3389/fmicb.2022.916280 -
Frontiers in Immunology 2022In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the...
In clinical practice, fecal microbiota transplantation (FMT) has been used to treat inflammatory bowel disease (IBD), and has shown certain effects. However, the selection of FMT donors and the mechanism underlying the effect of FMT intervention in IBD require further exploration. In this study, dextran sodium sulfate (DSS)-induced colitis mice were used to determine the differences in the protection of colitis symptoms, inflammation, and intestinal barrier, by FMT from two donors. Intriguingly, pre-administration of healthy bacterial fluid significantly relieved the symptoms of colitis compared to the ulcerative colitis (UC) bacteria. In addition, healthy donor (HD) bacteria significantly reduced the levels of inflammatory markers Myeloperoxidase (MPO) and Eosinophil peroxidase (EPO), and various pro-inflammatory factors, in colitis mice, and increased the secretion of the anti-inflammatory factor IL-10. Metagenomic sequencing indicated higher species diversity and higher abundance of anti-inflammatory bacteria in the HD intervention group, including , , , short-chain fatty acids (SCFAs)-producing bacterium , and secondary bile acids (SBAs)-producing bacterium . In the UC intervention group, the SCFA-producing bacterium , IBD-related bacterium , , and the conditional pathogen , were more abundant. Metabolomics analysis showed that the two types of FMT significantly modulated the metabolism of DSS-induced mice. Moreover, compared with the UC intervention group, indoleacetic acid and unsaturated fatty acids (DHA, DPA, and EPA) with anti-inflammatory effects were significantly enriched in the HD intervention group. In summary, these results indicate that FMT can alleviate the symptoms of colitis, and the effect of HD intervention is better than that of UC intervention. This study offers new insights into the mechanisms of FMT clinical intervention in IBD.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; Colitis; Colitis, Ulcerative; Dextran Sulfate; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Mice
PubMed: 35237276
DOI: 10.3389/fimmu.2022.836542 -
Microbiome Dec 2021Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to...
BACKGROUND
Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection. We studied fecal microbiome profiles, short-chain fatty acids, and blood plasma inflammatory cytokines of 109 HIV-1 seroconverters (SC) from the early, 1984-1985 phase of the HIV-1 pandemic in the Multicenter AIDS Cohort Study (MACS) before and after HIV-1 infection compared to 156 HIV-1-negative MACS MSM (negative controls [NC]).
RESULTS
We found that family Succinivibrionaceae, S24-7, Mogibacteriaceae, Coriobacteriaceae, and Erysipelotrichaceae were significantly higher (p<0.05), whereas Odoribacteraceae, Verucomicrobiaceae, Bacteroidaceae, Barnesiellaceae, and Rikenellaceae were significantly lower (p<0.05), in SC before HIV-1 infection compared to NC. At the species level, Prevotella stercorea, Eubacterium biforme, and Collinsella aerofaciens were significantly higher (p<0.05), and Eubacterium dolichum, Desulfovibrio D168, Alistipes onderdonkii, Ruminococcus torques, Bacteroides fragilis, Bacteroides caccae, Alistipes putredinis, Akkermansia muciniphila, Bacteroides uniformis, and Bacteroides ovatus were significantly lower (p<0.05) in SC before HIV-1 infection compared to NC. After HIV-1 infection, family Prevotellaceae and Victivallaceae and species Bacteroides fragilis and Eubacterium cylindroides were significantly higher (p<0.05) in SC who developed AIDS within 5 years compared to the SC who were AIDS free for more than 10 years without antiretroviral therapy (ART). In addition, family Victivallaceae and species Prevotella stercorea, Coprococcus eutactus, and Butyrivibrio crossotus were significantly higher (p<0.05) and Gemmiger formicilis and Blautia obeum were significantly lower (p<0.05) after HIV-1 infection in SC who developed AIDS within 5-10 years compared to the SC who were AIDS-free for more than 10 years without ART. Furthermore, plasma inflammatory cytokine levels of sCD14, sCD163, interleukin 6, and lipopolysaccharide binding protein were significantly higher in SC with p<0.05 before HIV-1 infection compared to NC.
CONCLUSIONS
Our results suggest that pathogenic changes in the gut microbiome were present in MSM several months prior to infection with HIV-1 in the early phase of the AIDS pandemic in the USA. This was associated with increased inflammatory biomarkers in the blood and risk for development of AIDS. Video abstract.
Topics: Cohort Studies; Female; Gastrointestinal Microbiome; HIV Infections; HIV-1; Homosexuality, Male; Humans; Male; Sexual and Gender Minorities
PubMed: 34879869
DOI: 10.1186/s40168-021-01168-w