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Oral Oncology Jan 2024Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut...
OBJECTIVES
Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis.
MATERIALS AND METHODS
Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients.
RESULTS
A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding.
CONCLUSION
Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.
Topics: Male; Humans; Female; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mucositis; Prospective Studies; Gastrointestinal Microbiome; Chemoradiotherapy
PubMed: 38006691
DOI: 10.1016/j.oraloncology.2023.106623 -
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 -
Nutrients Apr 2024Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in...
Zinc deficiency affects the physical and intellectual development of school-age children, while studies on the effects on intestinal microbes and metabolites in school-age children have not been reported. School-age children were enrolled to conduct anthropometric measurements and serum zinc and serum inflammatory factors detection, and children were divided into a zinc deficiency group (ZD) and control group (CK) based on the results of serum zinc. Stool samples were collected to conduct metagenome, metabolome, and diversity analysis, and species composition analysis, functional annotation, and correlation analysis were conducted to further explore the function and composition of the gut flora and metabolites of children with zinc deficiency. Beta-diversity analysis revealed a significantly different gut microbial community composition between ZD and CK groups. For instance, the relative abundances of , , , sp000434735, and were more enriched in the ZD group, while probiotic bacteria showed the reverse trend. The functional profile of intestinal flora was also under the influence of zinc deficiency, as reflected by higher levels of various glycoside hydrolases in the ZD group. In addition, saccharin, the pro-inflammatory metabolites, and taurocholic acid, the potential factor inducing intestinal leakage, were higher in the ZD group. In conclusion, zinc deficiency may disturb the gut microbiome community and metabolic function profile of school-age children, potentially affecting human health.
Topics: Humans; Gastrointestinal Microbiome; Zinc; Child; Male; Female; Feces; Bacteria; Intestinal Mucosa; Metabolome; Intestines
PubMed: 38732540
DOI: 10.3390/nu16091289 -
Nutrients Jan 2023Flavanones in peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain...
Flavanones in peel (CUP) have been used as therapeutic agents to reduce intestinal inflammation; however, the anti-inflammatory effects of their biometabolites remain ambiguous. Here, we identified aglycone-type flavanones, such as hesperetin and naringenin, which were more abundant in the bioconversion of the CUP than in the ethanol extracts of the CUP. We found that the bioconversion of the CUP induced the canonical nuclear factor-κB pathway via degradation of IκB in Caco-2 cells. To check the immune suppressive capacity of the aglycones of the CUP in vivo, we orally administered the bioconversion of the CUP (500 mg/kg) to mice for two weeks prior to the 3% dextran sulfate sodium treatment. The CUP-pretreated group showed improved body weight loss, colon length shortage, and intestinal inflammation than the control mice. We also found a significant decrease in the population of lamina propria Th17 cells in the CUP-pretreated group following dextran sodium sulfate (DSS) treatment and an increase in mRNA levels of occludin in CUP-treated Caco-2 cells. Pyrosequencing analysis revealed a decreased abundance of and an increased abundance of in the feces of the CUP-pretreated mice compared to those of the control mice. Overall, these findings suggest that the pre-administration of CUP biometabolites may inhibit the development of murine colitis by modulating intestinal permeability and the gut microbiome.
Topics: Humans; Mice; Animals; Caco-2 Cells; Citrus; Colitis; Colon; Inflammation; Bacteria; Flavanones; Permeability; Dextran Sulfate; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 36678190
DOI: 10.3390/nu15020319 -
Nature Microbiology Mar 2018Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial...
Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.
Topics: Adolescent; Adult; Child; Colitis, Ulcerative; Crohn Disease; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Gene Expression Profiling; Humans; Inflammatory Bowel Diseases; Longitudinal Studies; Male; Metagenomics; Phenotype; Transcription, Genetic; Young Adult
PubMed: 29311644
DOI: 10.1038/s41564-017-0089-z -
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 -
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 -
Scientific Reports Dec 2022Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the...
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and adolescents. The gut microbiota plays an important role in the pathophysiology of NAFLD through the gut-liver axis. Therefore, we aimed to investigate the genus and species of gut microbiota and their functions in children and adolescents with NAFLD. From May 2017 to July 2018, a total of 58 children and adolescents, including 27 abnormal weight (AW) (obese) NAFLD patients, 16 AW non-NAFLD children, and 15 healthy children, were enrolled in this study at Shenzhen Children's Hospital. All of them underwent magnetic resonance spectroscopy (MRS) to quantify the liver fat fraction. Stool samples were collected and analysed with metagenomics. According to body mass index (BMI) and MRS proton density fat fraction (MRS-PDFF), we divided the participants into BMI groups, including the AW group (n = 43) and the Lean group (n = 15); MRS groups, including the NAFLD group (n = 27) and the Control group (n = 31); and BMI-MRS 3 groups, including NAFLD_AW (AW children with NAFLD) (n = 27), Ctrl_AW (n = 16) (AW children without NAFLD) and Ctrl_Lean (n = 15). There was no difference in sex or age among those groups (p > 0.05). In the BMI groups, at the genus level, Dialister, Akkermansia, Odoribacter, and Alistipes exhibited a significant decrease in AW children compared with the Lean group. At the species level, Megamonas hypermegale was increased in the AW group, while Akkermansia muciniphila, Dialister invisus, Alistipes putredinis, Bacteroides massiliensis, Odoribacter splanchnicus, and Bacteroides thetaiotaomicron were decreased in AW children, compared to the Lean group. Compared with the Control group, the genus Megamonas, the species of Megamonas hypermegale and Megamonas rupellensis, increased in the NAFLD group. Furthermore, the genus Megamonas was enriched in the NAFLD_AW group, while Odoribacter, Alistipes, Dialister, and Akkermansia were depleted compared with the Ctrl_Lean or Ctrl_AW group at the genus level. Megamonas hypermegale and Megamonas rupellensis exhibited a significant increase in NAFLD_AW children compared with the Ctrl_Lean or Ctrl_AW group at the species level. Compared with healthy children, the pathways of P461-PWY contributed by the genus Megamonas were significantly increased in NAFLD_AW. We found that compared to healthy children, the genus Megamonas was enriched, while Megamonas hypermegale and Megamonas rupellensis were enriched at the species level in children and adolescents with NAFLD. This indicates that the NAFLD status and/or diet associated with NAFLD patients might lead to the enrichment of the genus Megamonas or Megamonas species.
Topics: Humans; Adolescent; Child; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; Firmicutes; Liver
PubMed: 36539432
DOI: 10.1038/s41598-022-25140-2 -
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 -
Obesity Surgery Sep 2020Distinct anatomical rearrangements of the gastrointestinal tract achieved by various types of bariatric surgery cause changes in nutrient intake and gut microbiota. The...
PURPOSE
Distinct anatomical rearrangements of the gastrointestinal tract achieved by various types of bariatric surgery cause changes in nutrient intake and gut microbiota. The contribution of such gut microbiota changes to remission of type 2 diabetes (T2D) remains unclear.
AIM
We examined gut microbiota changes following banded Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in a randomised study, in relation to T2D remission.
MATERIALS AND METHODS
Whole-metagenome shotgun sequencing was carried out on paired stool samples at pre- and 1-year post-surgery collected from 44 participants with T2D randomised to banded Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Taxonomic composition and predicted functional potential of the gut bacteria were identified using HUMANn2, and annotated using MetaCyc. Five-day dietary records (analysed using FoodWorks v8.0), body weight and diabetes status were recorded at both time points.
RESULTS
RYGB participants had higher percentage excess weight loss than SG (p = 0.01), even though dietary intake was similar at 1-year post-surgery. Similar proportions achieved diabetes remission (HbA1c < 48 mmol/mol without medications) after either RYGB (68%) or SG (59%). RYGB resulted in increased abundances of Firmicutes and Proteobacteria, while SG resulted in increased Bacteroidetes. Pre-surgery, an increased abundance of Eubacteriaceae (p = 0.01) and Alistipes putredinis (p = 0.01) was observed in those who went on to remit from T2D post-surgery. Following surgery, Lachnospiraceae (p = 0.04) and Roseburia (p = 0.01) species were more abundant in those who had achieved T2D remission.
CONCLUSIONS
Specific stool bacterial taxa may signal likelihood of T2D remission after bariatric surgery which is potentially mediated by increases in Lachnospiraceae and Roseburia.
Topics: Bacteroidetes; Bariatric Surgery; Diabetes Mellitus, Type 2; Gastrectomy; Gastric Bypass; Gastrointestinal Microbiome; Humans; Obesity, Morbid; Weight Loss
PubMed: 32447634
DOI: 10.1007/s11695-020-04684-0