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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 -
Scientific Reports Nov 2023To investigate the gut microbiota distribution and its functions in children with avoidant/restrictive food intake disorder (ARFID). A total of 135 children were...
To investigate the gut microbiota distribution and its functions in children with avoidant/restrictive food intake disorder (ARFID). A total of 135 children were enrolled in the study, including 102 children with ARFID and 33 healthy children. Fecal samples were analyzed to explore differences in gut microbiota composition and diversity and functional differences between the ARFID and healthy control (HC) groups via 16S rDNA and metagenomic sequencing. The gut microbiota composition and diversity in children with ARFID were different from those in heathy children, but there is no difference in the composition and diversity of gut microbiota between children at the age of 3-6 and 7-12 with ARFID. At the phylum level, the most abundant microbes in the two groups identified by 16S rDNA and metagenomic sequencing were the same. At the genus level, the abundance of Bacteroides was higher in the ARFID group (P > 0.05); however, different from the result of 16SrDNA sequencing, metagenomic sequencing showed that the abundance of Bacteroides in the ARFID group was significantly higher than that in the HC group (P = 0.041). At the species level, Escherichia coli, Streptococcus thermophilus and Lachnospira eligens were the most abundant taxa in the ARFID group, and Prevotella copri, Bifidobacterium pseudocatenulatum, and Ruminococcus gnavus were the top three microbial taxa in the HC group; there were no statistically significant differences between the abundance of these microbial taxa in the two groups. LefSe analysis indicated a greater abundance of the order Enterobacterales and its corresponding family Enterobacteriaceae, the family Bacteroidaceae and corresponding genus Bacteroides, the species Bacteroides vulgatus in ARFID group, while the abundance of the phylum Actinobacteriota and its corresponding class Actinobacteria , the order Bifidobacteriales and corresponding family Bifidobacteriaceae, the genus Bifidobacterium were enriched in the HC group. There were no statistically significant differences in the Chao1, Shannon and Simpson indices between the Y1 and Y2 groups (P = 0.1, P = 0.06, P = 0.06). At the phylum level, Bacillota, Bacteroidota, Proteobacteria and Actinobacteriota were the most abundant taxa in both groups, but there were no statistically significant differences among the abundance of these bacteria (P = 0.958, P = 0.456, P = 0.473, P = 0.065). At the genus level, Faecalibacterium was more abundant in the Y2 group than in the Y1 group, and the difference was statistically significant (P = 0.037). The KEGG annotation results showed no significant difference in gut microbiota function between children with ARFID and healthy children; however, GT26 was significantly enriched in children with ARFID based on the CAZy database. The most abundant antibiotic resistance genes in the ARFID group were the vanT, tetQ, adeF, ermF genes, and the abundance of macrolide resistance genes in the ARFID group was significantly higher than that in the HC group (P = 0.041). Compared with healthy children, children with ARFID have a different distribution of the gut microbiota and functional genes. This indicates that the gut microbiome might play an important role in the pathogenesis of ARFID.Clinical trial registration: ChiCTR2300074759.
Topics: Humans; Child; Anti-Bacterial Agents; Avoidant Restrictive Food Intake Disorder; Drug Resistance, Bacterial; Macrolides; Microbiota; Bacteria; Actinobacteria; Eating; RNA, Ribosomal, 16S
PubMed: 37985845
DOI: 10.1038/s41598-023-47760-y -
Translational Psychiatry Nov 2023Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently...
Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD.
Topics: Adult; Humans; Microbiota; Stress Disorders, Post-Traumatic; Gastrointestinal Microbiome; Feces; Biological Availability
PubMed: 37980332
DOI: 10.1038/s41398-023-02643-8 -
Nature Communications Nov 2023The early-life gut microbiome development has long-term health impacts and can be influenced by factors such as infant diet. Human milk oligosaccharides (HMOs), an...
The early-life gut microbiome development has long-term health impacts and can be influenced by factors such as infant diet. Human milk oligosaccharides (HMOs), an essential component of breast milk that can only be metabolized by some beneficial gut microorganisms, ensure proper gut microbiome establishment and infant development. However, how HMOs are metabolized by gut microbiomes is not fully elucidated. Isolate studies have revealed the genetic basis for HMO metabolism, but they exclude the possibility of HMO assimilation via synergistic interactions involving multiple organisms. Here, we investigate microbiome responses to 2'-fucosyllactose (2'FL), a prevalent HMO and a common infant formula additive, by establishing individualized microbiomes using fecal samples from three infants as the inocula. Bifidobacterium breve, a prominent member of infant microbiomes, typically cannot metabolize 2'FL. Using metagenomic data, we predict that extracellular fucosidases encoded by co-existing members such as Ruminococcus gnavus initiate 2'FL breakdown, thus critical for B. breve's growth. Using both targeted co-cultures and by supplementation of R. gnavus into one microbiome, we show that R. gnavus can promote extensive growth of B. breve through the release of lactose from 2'FL. Overall, microbiome cultivation combined with genome-resolved metagenomics demonstrates that HMO utilization can vary with an individual's microbiome.
Topics: Female; Child; Humans; Infant; Bifidobacterium; Trisaccharides; Milk, Human; Oligosaccharides; Microbiota
PubMed: 37973815
DOI: 10.1038/s41467-023-43279-y -
BioRxiv : the Preprint Server For... Oct 2023In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand...
In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand out due to their pivotal roles in various biological processes related to host health and nutrition. Here, we present CAZyLingua, the first tool that harnesses protein language model embeddings to build a deep learning framework that facilitates the annotation of CAZymes in metagenomic datasets. Our benchmarking results showed on average a higher F1 score (reflecting an average of precision and recall) on the annotated genomes of , and compared to the traditional sequence homology-based method in dbCAN2. We applied our tool to a paired mother/infant longitudinal dataset and revealed unannotated CAZymes linked to microbial development during infancy. When applied to metagenomic datasets derived from patients affected by fibrosis-prone diseases such as Crohn's disease and IgG4-related disease, CAZyLingua uncovered CAZymes associated with disease and healthy states. In each of these metagenomic catalogs, CAZyLingua discovered new annotations that were previously overlooked by traditional sequence homology tools. Overall, the deep learning model CAZyLingua can be applied in combination with existing tools to unravel intricate CAZyme evolutionary profiles and patterns, contributing to a more comprehensive understanding of microbial metabolic dynamics.
PubMed: 37961379
DOI: 10.1101/2023.10.23.563620 -
Frontiers in Immunology 2023Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious...
Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, (), can induce tuft cell proliferation in the proximal colon whereas the microbe's lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the and genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gβγ subunit inhibitor Gallein or the phospholipase Cβ2 (PLCβ2) inhibitor U73122 reduces -elicited tuft cell proliferation or IL-25 release or both. Furthermore, conditional knockout or knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium.
Topics: Taste; Ruminococcus; Signal Transduction; Transient Receptor Potential Channels; Colon
PubMed: 37954611
DOI: 10.3389/fimmu.2023.1259521 -
Frontiers in Microbiology 2023The early colonized gut microbiota during the newborn period has been reported to play important roles in the health and immunity of animals; however, whether they can...
The early colonized gut microbiota during the newborn period has been reported to play important roles in the health and immunity of animals; however, whether they can affect the growth performance of suckling lambs is still unclear. In this study, a total of 84 newborn lambs were assigned into LF-1 (top 15%), LF-2 (medium 70%), and LF-3 (bottom 15%) groups according to their average body weight gain at 30 days of age. Fecal samples of lambs (LF) as well as feces (MF), vagina (VAG), colostrum (COL), teat skin (TEAT) samples of ewes, and the air sediment (AIR) in the delivery room were collected 72 h after birth, and then the 16S rRNA gene was sequenced on the Illumina MiSeq platform. The results showed that the early colonized gut microbiota had a significant effect on the growth performance of suckling lambs with alpha and beta diversity ( < 0.05), and we observed that the contribution of early colonized bacteria on the growth performance of lambs increased with age (from BW at 25.35% to BW at 31.10%; from ADG at 33.02% to ADG at 39.79% by measuring the relative effects of factors that influence growth performance). The early colonized gut microbiota of suckling lambs with high growth performance was similar to that in VAG, MF, and AIR ( < 0.05). With the RandomForest machine learning algorithm, we detected 11, 11, 6, and 4 bacterial taxa at the genus level that were associated with BW, BW, ADG, and ADG of suckling lambs, respectively, and the correlation analysis showed that Butyricicoccus, Ruminococcus_gnavus_group, Ruminococcaceae_Other, and Fusobacterium could significantly affect the growth performance (BW, BW, ADG, and ADG) of suckling lambs ( < 0.05). In conclusion, the early colonized gut microbiota could significantly affect the growth performance of suckling lambs, and targeting the early colonized gut microbiota might be an alternative strategy to improve the growth performance of suckling lambs.
PubMed: 37954254
DOI: 10.3389/fmicb.2023.1273444 -
Carbohydrate Polymers Jan 2024Hydrocolloids are important food additives and have potential regulatory effects on gut microbiota. The development of colitis is closely related to changes in gut...
Hydrocolloids are important food additives and have potential regulatory effects on gut microbiota. The development of colitis is closely related to changes in gut microbiota. The effect of food hydrocolloids on the structure of the gut microbiota and their impact on colitis has not been well investigated. Therefore, this study investigated the effects of four hydrocolloids (carrageenan, guar gum, xanthan gum, and pectin) on colitis, and explored their regulatory effects on gut microbiota. The results indicated that pectin and guar effectively alleviated body weight loss and disease activity index, reduced inflammatory cytokine levels, and promoted short-chain fatty acids (SCFAs) production. They increased the abundance of Akkermansia muciniphila, Oscillospira, and Lactobacillus, and Akkermansia abundance had a negative correlation with the severity of colitis. In contrast, carrageenan and xanthan gum did not significantly improve colitis, and carrageenan reduced the production of SCFAs. Both carrageenan and xanthan gum increased the abundance of Ruminococcus gnavus, and Ruminococcus abundance was positively correlated with the severity of colitis. These findings suggest that food additives have an impact on host health and provide guidance for the diet of patients with colitis.
Topics: Humans; Animals; Mice; Gastrointestinal Microbiome; Carrageenan; Colitis; Food Additives; Pectins; Fatty Acids, Volatile; Colloids; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 37940266
DOI: 10.1016/j.carbpol.2023.121368 -
Scientific Reports Nov 2023Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant... (Clinical Trial)
Clinical Trial
Gastrointestinal symptoms are more prevalent in children with autism spectrum disorder (ASD) than in typically developing (TD) children. Constipation is a significant gastrointestinal comorbidity of ASD, but the associations among constipated autism spectrum disorder (C-ASD), microbiota and short-chain fatty acids (SCFAs) are still debated. We enrolled 80 children, divided into the C-ASD group (n = 40) and the TD group (n = 40). In this study, an integrated 16S rRNA gene sequencing and gas chromatography-mass spectrometry-based metabolomics approach was applied to explore the association of the gut microbiota and SCFAs in C-ASD children in China. The community diversity estimated by the Observe, Chao1, and ACE indices was significantly lower in the C-ASD group than in the TD group. We observed that Ruminococcaceae_UCG_002, Erysipelotrichaceae_UCG_003, Phascolarctobacterium, Megamonas, Ruminiclostridium_5, Parabacteroides, Prevotella_2, Fusobacterium, and Prevotella_9 were enriched in the C-ASD group, and Anaerostipes, Lactobacillus, Ruminococcus_gnavus_group, Lachnospiraceae_NK4A136_group, Ralstonia, Eubacterium_eligens_group, and Ruminococcus_1 were enriched in the TD group. The propionate levels, which were higher in the C-ASD group, were negatively correlated with the abundance of Lactobacillus taxa, but were positively correlated with the severity of ASD symptoms. The random forest model, based on the 16 representative discriminant genera, achieved a high accuracy (AUC = 0.924). In conclusion, we found that C-ASD is related to altered gut microbiota and SCFAs, especially decreased abundance of Lactobacillus and excessive propionate in faeces, which provide new clues to understand C-ASD and biomarkers for the diagnosis and potential strategies for treatment of the disorder. This study was registered in the Chinese Clinical Trial Registry ( www.chictr.org.cn ; trial registration number ChiCTR2100052106; date of registration: October 17, 2021).
Topics: Child; Humans; Autism Spectrum Disorder; Constipation; East Asian People; Fatty Acids, Volatile; Gastrointestinal Microbiome; Lactobacillales; Propionates; RNA, Ribosomal, 16S; Veillonellaceae
PubMed: 37925571
DOI: 10.1038/s41598-023-46566-2 -
World Journal of Gastroenterology Oct 2023The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small...
BACKGROUND
The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.
AIM
To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.
METHODS
Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.
RESULTS
The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal , , , and . Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.
CONCLUSION
The findings of this study demonstrate that the introduction of postoperative intestinal in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.
Topics: Rats; Animals; Gluconeogenesis; Glucagon-Like Peptide 1; Clostridium symbiosum; Jejunoileal Bypass; Diabetes Mellitus, Experimental; Rats, Sprague-Dawley; Gastric Bypass; Glucose; Homeostasis; Blood Glucose
PubMed: 37900993
DOI: 10.3748/wjg.v29.i39.5471