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Bacteroides fragilis is a Gram-negative commensal bacterium commonly found in the human colon, which differentiates into two genomospecies termed divisions I and II. Through a comprehensive collection of 694 B. fragilis whole genome sequences, we identify novel features distinguishing these divisions. Our study reveals a distinct geographic distribution with division I strains predominantly found in North America and division II strains in Asia. Additionally, division II strains are more frequently associated with bloodstream infections, suggesting a distinct pathogenic potential. We report differences between the two divisions in gene abundance related to metabolism, virulence, stress response, and colonization strategies. Notably, division II strains harbor more antimicrobial resistance (AMR) genes than division I strains. These findings offer new insights into the functional roles of division I and II strains, indicating specialized niches within the intestine and potential pathogenic roles in extraintestinal sites.ImportanceUnderstanding the distinct functions of microbial species in the gut microbiome is crucial for deciphering their impact on human health. Classifying division II strains as Bacteroides fragilis can lead to erroneous associations, as researchers may mistakenly attribute characteristics observed in division II strains to the more extensively studied division I B. fragilis. Our findings underscore the necessity of recognizing these divisions as separate species with distinct functions. We unveil new findings of differential gene prevalence between division I and II strains in genes associated with intestinal colonization and survival strategies, potentially influencing their role as gut commensals and their pathogenicity in extraintestinal sites. Despite the significant niche overlap and colonization patterns between these groups, our study highlights the complex dynamics that govern strain distribution and behavior, emphasizing the need for a nuanced understanding of these microorganisms.

Background: Pediatric cow milk allergies (CMA) can occur in immunoglobulin (Ig) E and non-IgE-mediated forms. Unlike IgE-mediated allergies, the mechanisms of disease pathogenesis in non-IgE-mediated food allergy and an association with microbiome has not been well established. Previous studies have identified the presence of altered humoral responses to gut bacteria in IgE mediated allergies. Here, we analyzed IgA, IgE and IgG responses to gut bacteria in subjects with either IgE or non-IgE mediated CMA to identify relative proportions of Ig-coated bacteria and characterize unique disease specific microbial signatures. Methods: Multi-parametric flow cytometry analysis was used to identify IgA, IgE and IgG responses to gut bacteria in CMA patients. Cell sorting of Ig coated gut bacteria was subsequently performed followed by high throughput 16S rRNA gene sequencing and specific patterns of humoral responses to gut bacteria assessed in each study group. Results: We identified significant alterations in IgA and IgG gut bacterial coating patterns in CMA subjects. Proportions of IgA-coated bacteria were decreased in IgE mediated CMA subjects without atopic dermatitis (ALL) and non-IgE mediated CMA subjects (ENP), compared to healthy controls (CON). In comparison, IgG-coated bacteria was significantly elevated in CMA subjects with atopic dermatitis (AD). Alpha and beta diversities displayed significant differences in IgA-, IgE-, and IgG-coated bacteria in AD and ENP groups. Significant differences in bacteria coated by IgA, IgE and IgG were detected at Phyla, Genus and Species levels and associated bacterial dysbiosis in IgE and non-IgE mediated allergies were identified. Linear discriminant analysis (LDA) effect size (LEFse) revealed unique disease associated bacterial signatures, including several pathogenic bacteria namely Bacteroides fragilis, Ruminococcus gnavus, Eubacterium dolichum, Fusobacterium, Clostridium neonatale and Robinsoniella peoriensis. Receiver operating characteristic curve analysis confirmed the efficiency of using the bacterial signatures identified as biomarkers for disease. Conclusions: Altered IgA and IgG responses to gut bacteria were identified in CMA subjects. The disease-specific responses were associated with alterations in bacterial diversity and concomitant dysbiosis of Ig-coated bacteria in IgE-mediated and non-IgE-mediated CMA pediatric subjects. The identification of pathogenic bacteria uniquely associated with different classes of allergic disease indicates a role of these bacteria in driving disease-specific pathological phenotypes. [ABSTRACT FROM AUTHOR]

Background: Phenotypic age (PhenoAge), a widely used marker of biological aging, has been shown to be a robust predictor of all-cause mortality and morbidity in different populations. Existing studies on biological aging have primarily focused on individual domains, resulting in a lack of a comprehensive understanding of the multi-systemic dysregulation that occurs in aging. Methods: PhenoAge was evaluated based on a linear combination of chronological age (CA) and 9 clinical biomarkers in 952 multi-ethnic Asian women of reproductive age. Phenotypic age acceleration (PhenoAgeAccel), an aging biomarker, represents PhenoAge after adjusting for CA. This study conducts an in-depth association analysis of PhenoAgeAccel with clinical, nutritional, lipidomic, gut microbiome, and genetic factors. Results: Higher adiposity, glycaemia, plasma saturated fatty acids, kynurenine pathway metabolites, GlycA, riboflavin, nicotinamide, and insulin-like growth factor binding proteins were positively associated with PhenoAgeAccel. Conversely, a healthier diet and higher levels of pyridoxal phosphate, all-trans retinol, betaine, tryptophan, glutamine, histidine, apolipoprotein B, and insulin-like growth factors were inversely associated with PhenoAgeAccel. Lipidomic analysis found 132 lipid species linked to PhenoAgeAccel, with PC(O-36:0) showing the strongest positive association and CE(24:5) demonstrating the strongest inverse association. A genome-wide association study identified rs9864994 as the top genetic variant (P = 5.69E-07) from the ZDHHC19 gene. Gut microbiome analysis revealed that Erysipelotrichaceae UCG-003 and Bacteroides vulgatus were inversely associated with PhenoAgeAccel. Integrative network analysis of aging-related factors underscored the intricate links among clinical, nutritional and lipidomic variables, such as positive associations between kynurenine pathway metabolites, amino acids, adiposity, and insulin resistance. Furthermore, potential mediation effects of blood biomarkers related to inflammation, immune response, and nutritional and energy metabolism were observed in the associations of diet, adiposity, genetic variants, and gut microbial species with PhenoAgeAccel. Conclusions: Our findings provide a comprehensive analysis of aging-related factors across multiple platforms, delineating their complex interconnections. This study is the first to report novel signatures in lipidomics, gut microbiome and blood biomarkers specifically associated with PhenoAgeAccel. These insights are invaluable in understanding the molecular and metabolic mechanisms underlying biological aging and shed light on potential interventions to mitigate accelerated biological aging by targeting modifiable factors. [ABSTRACT FROM AUTHOR]

Background: The implication of gut microbiota in the gut-kidney axis affects the pathophysiology of chronic kidney disease (CKD). Gut microbiota composition changes during CKD. We aimed to determine the relative frequency of important gut microbiota members in end-stage renal disease (ERSD) patients before and after renal transplantation compared to healthy subjects. Methods: Fifteen kidney transplant patients and 10 healthy subjects were recruited in this case-control prospective study. Fecal samples were taken sequentially from all patients before kidney transplantation, 1 week, and 1 month after it. The relative frequency of Lactobacillus spp., Bifidobacterium spp., Akkermansia muciniphila, Bacteroides fragilis, Escherichia coli, and Faecalibacterium pruasnitzii were determined through quantitative PCR. The obtained data was statistically analyzed by Stata software (Stata Corporation, USA). Results: The mean log number of all bacteria was significantly higher in healthy individuals than kidney transplant recipients (p < 0.001) except for Lactobacillus where the mean levels were almost identical in the two groups (p = 0.67). Moreover, 20% (3) of patients developed a urinary tract infection. Besides, 2 (13.33%) patients were diagnosed with delayed graft function. There were no statistically significant differences regarding changing trends in bacteria log number of Akkermansia muciniphila (p = 0.12), Bacteroid fragilis (p = 0.75), Bifidobacterium (p = 0.99), Escherichia coli (p = 0.5), Faecalibacterium (p = 0.98), and Lactobacilli (p = 0.93) between patients with and without delayed graft function (DGF). Conclusion: Gut microbiota composition in patients with ESRD was significantly different from those without it. However, the microbiota profile did not significantly differ in patients with and without DGF. [ABSTRACT FROM AUTHOR]

Anaerobic bacteria can cause many infections in children. Because they predominant in the normal human skin and mucous membranes bacterial flora, they are often associated with bacterial infections that originate from these sites. They are difficult to isolate from infectious sites, and are frequently missed. Anaerobic infections can occur in all body sites, including the central nervous system, oral cavity, head and neck, chest, abdomen, pelvis, skin, and soft tissues. Anaerobes colonize the newborn after birth and have been isolated in several types of neonatal infections. These include cellulitis of the site of fetal monitoring, neonatal aspiration pneumonia, bacteremia, conjunctivitis, omphalitis, and infant botulism. Management of anaerobic infection is challenging because of the slow growth of these bacteria, by their polymicrobial nature and by the growing antimicrobial resistance of anaerobic. Antimicrobial therapy may be the only treatment required, and may also be an adjunct to a surgical approach. Polymicrobial aerobic-anaerobic infection generally requires delivering antimicrobial therapy effective against all pathogens. The antibiotics with the greatest activity against anaerobes include carbapenems, beta-lactam/beta-lactamase inhibitor combinations, metronidazole, and chloramphenicol. Antimicrobial resistance is growing among anaerobic bacteria. The major increased in resistance have been reported with clindamycin, cephamycins, and moxifloxacin against Bacteroides fragilis group and related strains. Resistance patterns vary between different geographic areas and medical facilities. [ABSTRACT FROM AUTHOR]

DNA transfer is ubiquitous in the human gut microbiota, especially among species of the order Bacteroidales. In silico analyses have revealed hundreds of mobile genetic elements shared between these species, yet little is known about the phenotypes they encode, their effects on fitness, or pleiotropic consequences for the recipient's genome. In this work, we show that acquisition of a ubiquitous integrative conjugative element (ICE) encoding a type VI secretion system (T6SS) shuts down the native T6SS of Bacteroides fragilis. Despite inactivating this T6SS, ICE acquisition increases the fitness of the B. fragilis transconjugant over its progenitor by arming it with the new T6SS. DNA transfer causes the strain to change allegiances so that it no longer targets ecosystem members with the same element yet is armed for communal defense. [ABSTRACT FROM AUTHOR]

BACKGROUND RESULTS CONCLUSION Radix Astragali, commonly known as Astragalus, is a traditional medicinal and edible plant valued for its Qi‐tonifying properties. The dosage form of Radix Astragali processed with honey, known as honey‐processed Astragalus (HPA), shows improved Qi‐tonifying efficacy as compared to the raw product. Polysaccharides are the main bioactive ingredients in its aqueous extract. This study used a multiomics approach integrating microbiomics and metabolomics to elucidate the Qi‐tonifying mechanisms of honey‐processed Astragalus polysaccharides (HAPS).HAPS‐treated mice showed improved symptom scores, spleen and thymus indices, serum cytokines (tumor necrosis factor α, interleukin 1β) and intestinal mucosa secretory immunoglobulin A (SIgA) compared to the mice with spleen Qi deficiency. The analysis of gut microbiota indicated that HAPS regulated the relative abundance of Bacteroidetes, Bacteroides, Proteobacteria and Helicobacter, thereby improving intestinal flora dysbiosis in mice with spleen Qi deficiency. Eleven biomarkers in fecal metabolomics analysis were screened and identified, primarily associated with linoleic acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism and biosynthesis of unsaturated fatty acids. Furthermore, comprehensive analyses demonstrated that HAPS regulates palmitic acid and sphingolipid metabolism by modulating the abundance of Bacteroidetes, which in turn increased the levels of intestinal mucosal SIgA and restored intestinal mucosal immune function in mice with spleen Qi deficiency.Our findings revealed that HAPS is an essential active ingredient of HPA, and its Qi‐tonifying mechanism is closely related to the improvement of intestinal immune function. These findings lay the foundation for the application of HAPS as an immunomodulatory agent in health and dietary foods. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Gut microbiota (GM) is an invisible organ that plays an important role in human health. Increasing evidence suggests that polyphenols in pomegranate (punicalagin, PU) could serve as prebiotics to modulate the composition and function of GM. In turn, GM transform PU into bioactive metabolites such as ellagic acid (EA) and urolithin (Uro). In this review, the interplay between pomegranate and GM is thoroughly described by unveiling a dialog in which both actors seem to affect each other's roles. In a first dialog, the influence of bioactive compounds from pomegranate on GM is described. The second act shows how the GM biotransform pomegranate phenolics into Uro. Finally, the health benefits of Uro and that related molecular mechanism are summarized and discussed. Intake of pomegranate promotes beneficial bacteria in GM (e.g. Lactobacillus spp., Bifidobacterium spp.) while reducing the growth of harmful bacteria (e.g. Bacteroides fragilis group, Clostridia). Akkermansia muciniphila, and Gordonibacter spp., among others, biotransform PU and EA into Uro. Uro contributes to strengthening intestinal barrier and reducing inflammatory processes. Yet, Uro production varies greatly among individuals and depend on GM composition. Uro-producing bacteria and precise metabolic pathways need to be further elucidated therefore contributing to personalized and precision nutrition. HIGHLIGHTS: Gut microbiota plays a critical role in maintaining host health. Pomegranate is rich in bioactive components. Consumption of pomegranate positively modulates gut microbiota. Gut microbiota can transform ellagitannins in pomegranate into urolithin. Urolithin has high bioavailability and multiple health benefits. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum. Methods: In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95). Results: We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC. Conclusions: Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression. [ABSTRACT FROM AUTHOR]

Background: The gut microbiome is thought to play an important role in the development of colorectal cancer (CRC). However, as the gut microbiome varies widely based on diet, we sought to investigate the gut microbiome changes in patients with CRC in a South Asian population. Methods: The gut microbiome was assessed by 16s metagenomic sequencing targeting the V4 hypervariable region of the bacterial 16S rRNA in stool samples (n = 112) and colonic tissue (n = 36) in 112 individuals. The cohort comprised of individuals with CRC (n = 24), premalignant lesions (n = 10), healthy individuals (n = 50) and in those with diabetes (n = 28). Results: Overall, the relative abundances of genus Fusobacterium (p < 0.001), Acinetobacter (p < 0.001), Escherichia-Shigella (p < 0.05) were significantly higher in gut tissue, while Romboutsia (p < 0.01) and Prevotella (p < 0.05) were significantly higher in stool samples. Bacteroides and Fusobacterium were the most abundant genera found in stool samples in patients with CRC. Patients with pre-malignant lesions had significantly high abundances of Christensenellaceae, Enterobacteriaceae, Mollicutes and Ruminococcaceae (p < 0.001) compared to patients with CRC, and healthy individuals. Romboutsia was significantly more abundant (p < 0.01) in stool samples in healthy individuals compared to those with CRC and diabetes. Conclusion: Despite marked differences in the Sri Lankan diet compared to the typical Western diet, Bacteroides and Fusobacterium species were the most abundant in those with CRC, with Prevotella species, being most abundant in many individuals. We believe these results pave the way for possible dietary interventions for prevention of CRC in the South Asian population. [ABSTRACT FROM AUTHOR]

Efficient interbacterial competitions and diverse defensive strategies employed by various bacteria play a crucial role in acquiring a hold within a dense microbial community. The gut symbiont Bacteroides fragilis secretes an antimicrobial ubiquitin homologue (BfUbb) that targets an essential periplasmic PPIase to drive intraspecies bacterial competition. However, the mechanisms by which BfUbb enters the periplasm and its potential for interspecies antagonism remain poorly understood. Here, we employ transposon mutagenesis and identify a highly conserved TonB-dependent transporter SusCD (designated as ButCD) in B. fragilis as the BfUbb transporter. As a putative protein-related nutrient utilization system, ButCD is widely distributed across diverse Bacteroides species with varying sequence similarity, resulting in distinct import efficiency of Bacteroides ubiquitin homologues (BUbb) and thereby determining the species-specific toxicity of BUbb. Cryo-EM structural and functional investigations of the BfUbb–ButCD complex uncover distinctive structural features of ButC that are crucial for its targeting by BfUbb. Animal studies further demonstrate the specific and efficient elimination of enterotoxigenic B. fragilis (ETBF) in the murine gut by BfUbb, suggesting its potential as a therapeutic against ETBF-associated inflammatory bowel disease and colorectal cancer. Our findings provide a comprehensive elucidation of the species-specific toxicity exhibited by BUbb and explore its potential applications. The gut symbiont Bacteroides fragilis secretes an antimicrobial ubiquitin homologue (BfUbb) that drives intraspecies bacterial competition. Here, the authors identify a highly conserved TonB-dependent transporter SusCD in B. fragilis as the BfUbb transporter and show species-specific antagonism of BfUbb and the BfUbb bound SusCD complex structure, revealing potential therapeutic applications of BfUbb against enterotoxigenic B. fragilis-related diseases. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Bacteroides fragilis (ETBF) is believed to promote the malignant process of colorectal cancer (CRC), but the underlying molecular mechanism still needs to be revealed. CRC cells (SW480 and HCT-116) were treated with ETBF strain. Cell proliferation, invasion and, migration were evaluated by cell counting kit 8 assay, EdU assay, colony formation assay, transwell assay, and wound healing assay. Protein expression was analyzed by western blot. MicroRNA (miR)-139-3p and histone deacetylase 3 (HDAC3) expression levels in tissues and cells were determined by qRT-PCR. Xenograft tumor model was conducted to evaluate the effect of miR-139-3p on CRC tumor growth. ETBF treatment could promote CRC cell proliferation, invasion and migration. MiR-139-3p expression was decreased by ETBF, and its overexpression reversed the effect of ETBF on CRC cell progression. HDAC3 negatively regulated miR-139-3p expression, and its overexpression facilitated CRC cell behaviors via reducing miR-139-3p expression. Moreover, HDAC3 expression was increased by ETBF, and its knockdown also abolished ETBF-mediated CRC cell progression. Additionally, miR-139-3p overexpression could reduce CRC tumor growth in vivo. ETBF aggravated CRC proliferation and metastasis via the regulation of HDAC3/miR-139-3p axis. The discovery of ETBF/HDAC3/miR-139-3p axis may provide a new direction for CRC treatment. [ABSTRACT FROM AUTHOR]

Background: Folate (vitamin B9) occurs naturally mainly as tetrahydrofolate (THF), methyl-tetrahydrofolate (M-THF), and formyl-tetrahydrofolate (F-THF), and as dietary synthetic form (folic acid). While folate auxotrophy and prototrophy are known for several gut microbes, the specific folate forms produced by gut prototrophs and their impact on gut auxotrophs and microbiota remain unexplored. Methods: Here, we quantified by UHPLC-FL/UV folate produced by six predicted gut prototrophs (Marvinbryantia formatexigens DSM 14469, Blautia hydrogenotrophica 10507 T, Blautia producta DSM 14466, Bacteroides caccae DSM 19024, Bacteroides ovatus DSM 1896, and Bacteroides thetaiotaomicron DSM 2079 T) and investigated the impact of different folate forms and doses (50 and 200 µg/l) on the growth and metabolism of the gut auxotroph Roseburia intestinalis in pure cultures and during fecal anaerobic batch fermentations (48 h, 37 °C) of five healthy adults. Results: Our results confirmed the production of folate by all six gut strains, in the range from 15.3 ng/ml to 205.4 ng/ml. Different folate forms were detected, with THF ranging from 12.8 to 41.4 ng/ml and 5-MTHF ranging from 0.2 to 113.3 ng/ml, and being detected in all strains. Natural folate forms, in contrast to folic acid, promoted the growth and metabolism of the auxotroph R. intestinalis L1-82, with dose-dependent effects. During fecal batch fermentations, folate forms at both levels had no detectable effect on total bacteria concentration, on gut community composition and metabolic activity and on Roseburia spp. abundance, compared to the control without folate addition. Conclusions: Our study demonstrates for the first time in vitro the production of different natural folate forms by predicted gut prototrophs and the stimulation on the growth of the folate auxotrophic butyrate-producing R. intestinalis L1-82. Surprisingly, folate did not impact fecal fermentations. Our data suggest that the dietary folate forms at the tested levels may only have limited effects, if any, on the human gut microbiota in vivo. [ABSTRACT FROM AUTHOR]

Background: Accurate identification of infectious diseases using molecular techniques, such as PCR and NGS, is well-established. This study aims to assess the utility of Bactfast and Fungifast in diagnosing bloodstream infections in ICU settings, comparing them against traditional culture methods. The objectives include evaluating sensitivity and specificity and identifying a wide range of pathogens, including non-culturable species. Methods: We collected 500 non-duplicate blood samples from ICU patients between January 2023 and December 2023. Specimens underwent traditional culture, MALDI-TOF, VITEK®2 compact system, and NGS-based Bactfast and Fungifast analyses. Results: Out of the 500 samples, 26.8% (n=134) showed bacterial growth via traditional culture methods, while 4.8% (n=24) were positive for fungal growth. MALDI-TOF and VITEK®2 compact system yielded comparable results, identifying 26.4% (n=132) of specimens with bacterial growth. NGS-based Bactfast detected bacterial presence in 38.2% (n=191) of samples, including non-culturable bacteria missed by traditional methods. However, NGS-based Fungifast showed concordant fungal detection rates with culture methods. Among identified pathogens by culture method included Klebsiella pneumoniae 20.89% (n=28), Enterococcus faecalis 18.65% (n=25), Escherichia coli 15.67% (n=21), Pseudomonas aeruginosa 12.68% (n=17), Acinetobacter baumannii 10.44% (n=14), various Streptococcus species 7.46% (n=10), Mycobacterium tuberculosis 6.71% (n=9), Mycobacterium abscessus 4.47% (n=6), and Salmonella spp 2.98% (n=4). Non-culture-based NGS identified additional (n=33) pathogens, including Klebsiella pneumoniae 27.27% (n=9), Bacteroides fragilis 21.21% (n=7), Aerococcus viridans 15.15% (n=5), Elizabethkingia anopheles 12.12% (n=4), Aeromonas salmonicida 9% (n=3), Clostridium 9% (n=3), and Bacteroides vulgatus 6% (n=2). Candida albicans was reported in 5% (n=24) of samples by both methods. Conclusion: NGS-based Bactfast and Fungifast demonstrate high sensitivity in identifying a wide array of bacterial and fungal pathogens in ICU patients, outperforming traditional culture methods in detecting non-culturable organisms. These molecular assays offer rapid and comprehensive diagnostic capabilities, potentially improving clinical outcomes through timely and accurate pathogen identification. [ABSTRACT FROM AUTHOR]

Introduction: Some studies have found that probiotics have the potential to treat PD, and earthworm protein is a traditional Chinese medicine used for the treatment of PD. The purpose of this study was to evaluate the safety and efficacy of Bacteroides fragilis 839 (BF839) + earthworm protein supplement as an adjunctive therapy for PD and to observe changes in the gut microbiota. Methods: Forty-six patients with PD were recruited for a 12-week 1:1 randomized, double-blind, placebo-controlled clinical trial to evaluate changes in motor and some non-motor symptom scores and detect metagenomic changes in the gut microbiota. Results: From baseline to 12 weeks, compared with placebo, the trial group showed significant reductions in the United Parkinson's Disease Rate Scale (UPDRS) total score (-7.74 ± 5.92 vs. -1.83 ± 4.14, p < 0.001), UPDRS part I (-0.72 ± 0.81 vs. -0.20 ± 0.72, p = 0.026), UPDRS part II (-2.50 ± 2.24 vs. -0.22 ± 1.98, p = 0.001), UPDRS part III (-3.43 ± 3.42 vs. -1.33 ± 2.65, p = 0.024), and UPDRS part IV (-1.13 ± 1.19 vs. -0.15 ± 0.57, p = 0.001). Significant reductions in the Hamilton Depression Scale-24 score (-3.91 ± 3.99 vs. +1.15 ± 3.42, p < 0.001), Self-Rating Anxiety Scale scores (-7.04 ± 5.71 vs. -1.23 ± 2.34, p < 0.001), and Constipation scoring system scores (-8.59 ± 4.75 vs. 0.27 ± 1.24, p < 0.001), were also noted. In the trial group, one patient experienced mild eczema and one suffered low blood pressure, which could not be conclusively attributed to supplementation. Compared to the placebo group, the trial group showed a marked increase in Enterococcus faecium and a decrease in Klebsiella. Conclusion: This study is the first to report that probiotics plus earthworm protein can remarkably improve the motor and some non-motor symptoms of PD without serious adverse effects. However, further clinical trials and exploration of the underlying mechanisms are required. [ABSTRACT FROM AUTHOR]

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Pathogenic changes in gut microbial composition precede the onset of HIV-1 infection in men who have sex with men (MSM). This process is associated with increased levels of systemic inflammatory biomarkers and risk for AIDS development. Using mediation analysis framework, in this report we link the effects of unprotected receptive intercourse among MSM prior to primary HIV-1 infection to higher levels of proinflammatory cytokines sCD14 and sCD163 in plasma and a significant decrease in the abundance of A. muciniphila, B. caccae, B. fragilis, B. uniformis, Bacteroides spp., Butyricimonas spp., and Odoribacter spp., and a potential increase in the abundance of Dehalobacterium spp. and Methanobrevibacter spp. in stools of MSM with the highest number of sexual partners. These differences in microbiota, together with a reduction in the pairwise correlations among commensal and short-chain fatty acid-producing bacteria with a number of sexual partners, support an increase in gut dysbiosis with the number of sexual partners. These results demonstrate the interconnectedness of sexual behavior, immune response, and microbiota composition, notably among MSM participating in high-risk sexual behaviors. Sexual behavior among men who have receptive anal intercourse with men is linked to changes in the gut microbiome and systemic inflammation leading to HIV-1 infection. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is the major bacterial cause of diarrheal diseases in pigs, particularly at young ages, resulting in significant costs to swine farming. The pathogenicity of ETEC is largely dependent on the presence of fimbriae and the ability to produce toxins. Fimbriae are responsible for their initial adhesion to the intestinal epithelial cells, leading to the onset of infection. In particular, the F4 type (K88) fimbriae are often attributed to neonatal infections and have also been associated with post-weaning diarrheal infections. This disease is traditionally prevented or treated with antibiotics, but their use is being severely restricted due to the emergence of resistant bacteria and their impact on human health. Emerging approaches such as aptamers that target the F4-type fimbriae and block the initial ETEC adhesion are a promising alternative. The aim of this study is to assess the effectiveness of two aptamers, Apt31 and Apt37, in controlling ETEC infection in the G. mellonella in vivo model. Initially, the dissociation constant (KD) of each aptamer against ETEC was established using real-time quantitative PCR methodology. Subsequently, different concentrations of the aptamers were injected into Galleria mellonella to study their toxicity. Afterwards, the anti-ETEC potential of Apt31 and Apt37 was assessed in the larvae model. The determined KD was 81.79 nM (95% CI: 31.21-199.4 nM) and 50.71 nM (95% CI: 26.52-96.15 nM) for the Apt31 and Apt37, respectively, showing no statistical difference. No toxicity was observed in G. mellonella following injection with both aptamers at any concentration. However, the administration of Apt31 together with ETEC-F4+ in G. mellonella resulted in a significant improvement of approximately 30% in both larvae survival and health index compared to ETEC-F4+ alone. These findings suggest that aptamers have promising inhibitory effect against ETEC infections and pave the way for additional in vivo studies. [ABSTRACT FROM AUTHOR]

The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance. [ABSTRACT FROM AUTHOR]

This collection of articles explores various aspects of gastrointestinal health and the role of microbes in the gut. The first article discusses the effects of simethicone on duodenal bacteria, finding that even low concentrations of the anti-foaming agent can suppress their growth. The second article proposes a new method to detect pathogenic T cells in coeliac disease, which could be used to test the effectiveness of drugs targeting these cells. The third article examines the prevalence of gastric mucosal changes in coeliac disease patients, finding no association between these changes and the disease. The fourth article investigates the role of colonic mucus in protecting against the genotoxic effects of a toxin produced by Bacteroides fragilis, as well as the development of a model to study how microbes influence the intestinal epithelium. These studies provide valuable insights into the complex interactions between microbes and the gut, potentially leading to new diagnostic and treatment approaches for gastrointestinal diseases. [Extracted from the article]

The anti-inflammatory properties of Bacteroides fragilis vesicles were studied in a rat model of dextran sodium sulfate-induced colitis. According to the histology results, addition of B. fragilis vesicles to the therapy promoted colon repair. Evaluation of the disease activity index confirms the high rate of colon recovery: against the background of vesicle administration, the absence of blood in stool, normal stool consistency, and body weight normalization were observed. [ABSTRACT FROM AUTHOR]

The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC). [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate antibiotic susceptibility and antimicrobial resistance trends among clinically significant anaerobes in Kuwait hospitals from 2013 to 2022, comparing these findings with data from 2002 to 2012. Methods: The study prospectively collected 2,317 anaerobic isolates from various body sites across four Kuwaiti hospitals between January 2013 and December 2022. The minimum inhibitory concentrations for 11 antianaerobic antibiotics were determined using E-test methodology. The study analyzed trends and resistance rates across two periods: 2013–2017 and 2018–2022, using statistical analysis for resistance comparison. Results: Of the 2,317 isolates, most were from wounds (42.2%), fluids (28.0%), and tissues (20.5%). Bacteroides fragilis was the most common pathogen (34.0%), followed by Prevotella bivia (13.4%). Over 90% of isolates were susceptible to imipenem, meropenem, tigecycline, and metronidazole, whereas lower susceptibility was observed for penicillin, amoxicillin–clavulanic acid, and clindamycin. Notable differences in resistance profiles since 2002 were observed, especially in amoxicillin–clavulanic acid, piperacillin, piperacillin–tazobactam, and clindamycin. Conclusion: Owing to detected resistance to all antibiotics, susceptibility testing for anaerobic isolates is recommended in severe infections to ensure effective antimicrobial therapy. Continuous surveillance is crucial for developing antibiotic policies to manage invasive anaerobic infections. [ABSTRACT FROM AUTHOR]

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Bacteroides fragilis is a universal member of the dominant commensal gut phylum Bacteroidetes. Its fermentation products and abundance have been linked to obesity, inflammatory bowel disease, and other disorders through its effects on host metabolic regulation and the immune system. As of yet, there has been no curated systems-level characterization of B. fragilis metabolism that provides a comprehensive analysis of the link between human diet and B. fragilis metabolic products. To address this, we developed a genome-scale metabolic model of B. fragilis strain 638R. The model iMN674 contains 1,634 reactions, 1,362 metabolites, three compartments, and reflects the strains ability to utilize 142 metabolites. Predictions made with this model include its growth rate and efficiency on these substrates, the amounts of each fermentation product it produces under different conditions, and gene essentiality for each biomass component. The model highlights and resolves gaps in knowledge of B. fragilis carbohydrate metabolism and its corresponding transport proteins. This high quality model provides the basis for rational prediction of B. fragilis metabolic interactions with its environment and its host.

Green nanomaterials have been extensively used in the environmental and agricultural applications due to their advantages of biocompatibility, eco-friendly, and cost-effectiveness. In this study, we have employed P. granatum leaf extract as a capping and stabilizing agent for the biofabrication of nickel oxide (NiO) nanoparticles to remove dyes effectively. The key factors which influenced the removal of Methylene Blue (MB) and Congo Red (CR) dyes under both visible and UV light exposure were identified. The experimental findings demonstrated the significant degradation efficiencies, with MB and CR reaching degradation levels of 91.7 % and 81.2 %, respectively. Furthermore, the face-centered cubic (fcc) structure with a space group of (Fm3m) of NiO was observed from the powder X-ray diffraction (XRD) analysis. Additionally, the morphology of NiO nanoparticles were investigated using scanning electron microscopy (SEM). Morphological analysis using high-resolution transmission electron microscopes (HR-TEM) with energy-dispersive X-ray spectroscopy (EDX), revealed the formation of spherical, cylindrical, and rod-shaped, nanoparticles and their elemental composition respectively. Fourier-transform infrared spectroscopy (FTIR) analysis has provided valuable insights into the molecular vibrations and the formation of Ni-O bonds within the NiO lattice. In the PL spectrum, the observed emission peaks at 484 and 545 nm indicate the presence of defects within the NiO structure. Raman spectroscopy further confirms the 2M vibrational mode and a reduction in antiferromagnetic coupling in the samples. Additionally, investigations on NiO nanoparticles at concentrations ranging from 50 to 500 mg/ml have exhibited their influence on bacterial activity against Bacillus cereus and Bacteroides fragilis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify potential novel drug targets for Bacteroides fragilis infections using bioinformatics techniques, such as subtractive and comparative genomics. Bacteroides fragilis is a frequently isolated anaerobic pathogen, particularly in the human digestive tract, where its pathogenesis and persistence are influenced by various virulence factors. By understanding these factors, the study aims to explore alternative therapeutic strategies and provide insights for the development of treatments against B. fragilis infections, particularly as alternatives to antibiotic therapy. A comparative subtractive genomic analysis was performed against the B. fragilis (strain CL07T12C05) to identify unique drug targets. The analysis includes the identification of non-paralogous, non-homologous, essential, and drug target like proteins. Moreover, a comprehensive structural analysis of the protein was conducted utilizing structure modeling and validation techniques, along with network topology analysis. Furthermore, a library comprising approximately 9000 FDA-approved compounds accessible in the DrugBank database was employed to conduct virtual screenings for compounds effective against the designated drug target. The top shortlisted compounds were further studied by employing MD simulations using GROMACS. This approach was chosen due to the established safety, efficacy, pharmacokinetics, and toxicity profiles of these compounds. As a result, B. fragilis (strain CL07T12C05) was found to possess 4595 proteins. Among these, 3518 were identified as non-homologous, 1508 deemed essential for bacterial viability, 348 exhibited drug-like properties, 203 were implicated in virulence, and 135 displayed antibiotic resistance. Following an extensive literature review, the protein Sialic acid O-acetyltransferase was chosen through a hierarchical shortlisting process as a potential therapeutic target. The ongoing research facilitated the repurposing of drug compounds: DB12411, DB02112, DB03591, and DB00192, as cost-effective medications against B. fragilis related infections. MD simulations analysis showed that DB12411 may be a potential drug candidate against Sialic acid O-acetyltransferase from B. fragilis. Through subtractive and comparative genomic analysis, Sialic acid O-acetyltransferase was identified as a promising drug target against Bacteroides fragilis. The findings indicate that compounds targeting this protein could potentially be effective in treating B. fragilis infections. However, further experimental validation is required to conclusively confirm their efficacy. [ABSTRACT FROM AUTHOR]

Isomalto/malto-polysaccharides (IMMPs) are a novel type of soluble dietary fibres with a prebiotic potential promoting growth of beneficial microbes in the gut. However, the mode of action of IMMPs remains unknown. Previous studies on IMMPs showed an increase in total bacteria, especially lactobacilli, and higher production of short chain fatty acids (SCFA) when IMMPs were fed to rats or used during in vitro fermentation. Here we used metatranscriptomics to investigate how IMMPs with different amounts of α − (1 → 6) glycosidic linkages affected microbial function during incubation with human fecal inoculum. We showed that active microbial community dynamics during fermentation varied depending on the type of IMMP used and that the observed changes were reflected in the community gene expression profiles. Based on metatranscriptome analysis, members of Bacteroides, Lactobacillus and Bifidobacterium were the predominant degraders of IMMPs, and the increased gene expression in these bacteria correlated with high amounts of α − (1 → 6) glycosidic linkages. We also noted an increase in relative abundance of these bacteria and an activation of pathways involved in SCFA synthesis. Our findings could provide a baseline for more targeted approaches in designing prebiotics for specific bacteria and to achieve more controlled modulation of microbial activity towards desired health outcomes. [ABSTRACT FROM AUTHOR]

Sanfilippo syndrome, or mucopolysaccharidosis type III (MPS III), is a rare lysosomal disease caused by congenital enzymatic deficiencies in heparan sulfate (HS) degradation, leading to organ dysfunction. The most severe hallmark of MPS III comprises neurological alterations, although gastrointestinal symptoms (GISs) have also been shown to be relevant in many patients. Here, we explored the contribution of the gut microbiota to MPS III GISs. We analyzed the composition and functionality of the gut microbiota in two MPS III siblings with the same mutation (c.544C > T, c.1080delC, in the SGSH gene) and the same diet, but with differences in their GISs, including recurrent diarrhea in one of them. Using 16S sequencing, we observed that the MPS III patients exhibited decreased alpha diversity and a lower abundance of Lachnospiraceae and Bifidobacteriaceae accompanied by a higher abundance of the Ruminococcaceae and Rikenellaceae families than the healthy control subjects. Comparing siblings, we found an increased abundance of Bacteroidaceae and a lower abundance of Ruminococcaceae and Akkermansiaceae in the GIS-free patient. This patient also had a higher relative abundance of Sus genes (SusA, SusB, SusE, and SusG) involved in glycosaminoglycan metabolism. We found higher HS levels in the stool of the two MPS III patients than in healthy volunteers, particularly in the patient with GISs. Functionally, whole fecal metabolites from the patient with GISs induced oxidative stress in vitro in healthy monocytes. Finally, the Bacteroides thetaiotaomicron strain isolated from MPS III stool samples exhibited HS degradation ability. Overall, our results reveal different microbiota compositions and functionalities in MPS III siblings, who exhibited differential gastrointestinal symptomatology. Our study may serve as a gateway to explore the impact of the gut microbiota and its potential to enhance the quality of life in Sanfilippo syndrome patients. [ABSTRACT FROM AUTHOR]

Fecal microbial transplantation (FMT) offers promise for treating ulcerative colitis (UC), though the mechanisms underlying treatment failure are unknown. This study harnessed longitudinally collected colonic biopsies (n = 38) and fecal samples (n = 179) from 19 adults with mild-to-moderate UC undergoing serial FMT in which antimicrobial pre-treatment and delivery mode (capsules versus enema) were assessed for clinical response (≥ 3 points decrease from the pre-treatment Mayo score). Colonic biopsies underwent dual RNA-Seq; fecal samples underwent parallel 16S rRNA and shotgun metagenomic sequencing as well as untargeted metabolomic analyses. Pre-FMT, the colonic mucosa of non-responsive (NR) patients harbored an increased burden of bacteria, including Bacteroides, that expressed more antimicrobial resistance genes compared to responsive (R) patients. NR patients also exhibited muted mucosal expression of innate immune antimicrobial response genes. Post-FMT, NR and R fecal microbiomes and metabolomes exhibited significant divergence. NR metabolomes had elevated concentrations of immunostimulatory compounds including sphingomyelins, lysophospholipids and taurine. NR fecal microbiomes were enriched for Bacteroides fragilis and Bacteroides salyersiae strains that encoded genes capable of taurine production. These findings suggest that both effective mucosal microbial clearance and reintroduction of bacteria that reshape luminal metabolism associate with FMT success and that persistent mucosal and fecal colonization by antimicrobial-resistant Bacteroides species may contribute to FMT failure. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. Methods: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). Results: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product—vaccarin (VAC)—that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. Conclusions: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate whether alpha‐galactosylceramide (α‐GalCer)‐producing Bacteroides fragilis could induce natural killer T (NKT) cells in nonobese diabetic (NOD) mice and reduce their diabetes incidence. Methods: Five‐week‐old female NOD mice were treated orally with B. fragilis, and islet pathology and diabetes onset were monitored. Immune responses were analyzed by flow cytometry and multiplex technology. Effects of ultraviolet (UV)‐killed α‐GalCer‐producing B. fragilis and their culture medium on invariant NKT (iNKT) cells were tested ex vivo on murine splenocytes, and the immunosuppressive capacity of splenocytes from B. fragilis‐treated NOD mice were tested by adoptive transfer to nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Results: B. fragilis reduced the diabetes incidence from 69% to 33% and the percent of islets with insulitis from 40% to 7%, which doubled the serum insulin level compared with the vehicle‐treated control mice. Furthermore, the early treatment reduced proinflammatory mediators in the serum, whereas the proportion of CD4+ NKT cell population was increased by 33%. B. fragilis growth media stimulated iNKT cells and anti‐inflammatory M2 macrophages ex vivo in contrast to UV‐killed bacteria, which had no effect, strongly indicating an α‐GalCer‐mediated effect. Adoptive transfer of splenocytes from B. fragilis‐treated NOD mice induced a similar diabetes incidence as splenocytes from untreated NOD mice. Conclusions: B. fragilis induced iNKT cells and M2 macrophages and reduced type 1 diabetes in NOD mice. The protective effect seemed to be more centered on gut–pancreas interactions rather than a systemic immunosuppression. B. fragilis should be considered for probiotic use in individuals at risk of developing type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD. [ABSTRACT FROM AUTHOR]

Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty of co-culturing microbes with intestinal epithelial cells. On one hand the gut bacteria are a mix of facultative, aerotolerant or obligate anaerobes, while the intestinal epithelium requires oxygen for growth and function. Thus, a coculture system that can recreate these contrasting oxygen requirements is critical step towards our understanding microbial-host interactions in the human gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC) system, a simple and cost-effective method for coculturing anaerobic intestinal bacteria with human intestinal organoids (HIOs). Using commensal anaerobes with varying degrees of oxygen tolerance, such as nano-aerobe Bacteroides thetaiotaomicron and strict anaerobe Blautia sp., we demonstrate that IOPC can successfully support 24–48 hours HIO-microbe coculture. The IOPC recapitulates the contrasting oxygen conditions across the intestinal epithelium seen in vivo. The IOPC cultured HIOs showed increased barrier integrity, and induced expression of immunomodulatory genes. A transcriptomic analysis suggests that HIOs from different donors show differences in the magnitude of their response to coculture with anaerobic bacteria. Thus, the IOPC system provides a robust coculture setup for investigating host-microbe interactions in complex, patient-derived intestinal tissues, that can facilitate the study of mechanisms underlying the role of the microbiome in health and disease. [ABSTRACT FROM AUTHOR]

Relapsing fever (RF), a vector-borne disease caused by Borrelia spp., is characterized by recurring febrile episodes due to repeated bouts of bacteremia. RF spirochetes can be geographically and phylogenetically divided into two distinct groups; Old World RF Borrelia (found in Africa, Asia, and Europe) and New World RF Borrelia (found in the Americas). While RF is a rarely reported disease in the Americas, RF is prevalent in endemic parts of Africa. Despite phylogenetic differences between Old World and New World RF Borrelia and higher incidence of disease associated with Old World RF spirochete infection, genetic manipulation has only been described in New World RF bacteria. Herein, we report the generation of genetic tools for use in the Old World RF spirochete, Borrelia duttonii. We describe methods for transformation and establish shuttle vector- and integration-based approaches for genetic complementation, creating green fluorescent protein (gfp)-expressing B. duttonii strains as a proof of principle. Allelic exchange mutagenesis was also used to inactivate a homolog of the Borrelia burgdorferi p66 gene, which encodes an important virulence factor, in B. duttonii and demonstrate that this mutant was attenuated in a murine model of RF. Finally, the B. duttonii p66 mutant was complemented using shuttle vector- and cis integration-based approaches. As expected, complemented p66 mutant strains were fully infectious, confirming that P66 is required for optimal mammalian infection. The genetic tools and techniques reported herein represent an important advancement in the study of RF Borrelia that allows for future characterization of virulence determinants and colonization factors important for the enzootic cycle of Old World RF spirochetes. Author summary: Relapsing fever is a globally distributed, vector-borne bacterial infection that is characterized by recurring febrile episodes. The causative Borrelia spp. were identified over 100 years ago, but little is known regarding factors required for mammalian infection or vector colonization/transmission. Relapsing fever Borrelia can be geographically and phylogenetically divided into distinct clades; New World, found in the Americas, and Old World, found in Africa, Europe, and Asia. Although Old World relapsing fever Borrelia represent major causes of disease in endemic regions of the world, genetic studies aimed at identifying bacterial gene products required during the tick-vertebrate infectious cycle have focused on the less commonly reported New World relapsing fever Borrelia. Herein, we begin to address this knowledge gap by developing techniques and molecular tools for genetic manipulation of the Old World tick-borne relapsing fever spirochete, Borrelia duttonii. This genetic system will lay the foundation for future studies aimed at identifying bacterial factors required during the enzootic cycle of B. duttonii. [ABSTRACT FROM AUTHOR]

SUMMARY: Brassica carinata (BBCC) commonly referred to as Ethiopian mustard is a natural allotetraploid containing the genomes of Brassica nigra (BB) and Brassica oleracea (CC). It is an oilseed crop endemic to the northeastern regions of Africa. Although it is under limited cultivation, B. carinata is valuable as it is resistant/highly tolerant to most of the pathogens affecting widely cultivated Brassica species of the U's triangle. We report a chromosome‐scale genome assembly of B. carinata accession HC20 using long‐read Oxford Nanopore sequencing and Bionano optical maps. The assembly has a scaffold N50 of ~39.8 Mb and covers ~1.11 Gb of the genome. We compared the long‐read genome assemblies of the U's triangle species and found extensive gene collinearity between the diploids and allopolyploids with no evidence of major gene losses. Therefore, B. juncea (AABB), B. napus (AACC), and B. carinata can be regarded as strict allopolyploids. We cataloged the nucleotide‐binding and leucine‐rich repeat immune receptor (NLR) repertoire of B. carinata and, identified 465 NLRs, and compared these with the NLRs in the other Brassica species. We investigated the extent and nature of early‐generation genomic interactions between the constituent genomes of B. carinata and B. juncea in interspecific crosses between the two species. Besides the expected recombination between the constituent B genomes, extensive homoeologous exchanges were observed between the A and C genomes. Interspecific crosses, therefore, can be used for transferring disease resistance from B. carinata to B. juncea and broadening the genetic base of the two allotetraploid species. Significance Statement: We report a highly contiguous genome assembly of allotetraploid mustard Brassica carinata HC20 (BBCC) which contains resistance to many diseases affecting the other extensively cultivated Brassica species of the U's triangle. Comparative analyses of the long‐read assemblies of the six Brassica species revealed high gene collinearity between the three diploid and their allotetraploid species. We tracked the early‐generation genomic interactions between the subgenomes of B. carinata (BBCC) and B. juncea (AABB) in their interspecific crosses using molecular karyotyping and proposed strategies to utilize this information for genomic introgressions. [ABSTRACT FROM AUTHOR]

Airborne microorganisms, an emerging global health threat, have attracted extensive studies. However, few attentions have been paid to the seasonal distribution of airborne pathogens, in particular their associations with antibiotic resistance genes (ARGs). To this end, two-week daily PM2.5 samples were consecutively collected from Nanchang in four seasons, and the human-tohuman pathogens were screened based on high-throughput sequencing. The results showed that there were 20 pathogenic taxa in PM2.5 in Nanchang, and the highest relative abundance of pathogens was observed in winter (5.84%), followed by summer (3.51%), autumn (2.66%), and spring (1.80%). Although more than half of pathogenic taxa were shared by the four seasons, the analysis of similarities showed that pathogenic community was shaped by season (r = 0.16, p < 0.01). Co-occurrence network analysis disclosed significant interactions among pathogens in each season. Moreover, some dominant pathogens such as Plesiomonas shigelloides, Bacteroides fragilis, and Escherichia-Shigella were hub pathogens. In addition, PICRUSt2 predicted that there were 35 high-risk ARG subtypes in PM2.5, and the pathogens had strongly positive correlations with these ARGs. Even some pathogens like Plesiomonas shigelloides, Bacteroides fragilis, Aeromonas, Citrobacter, may be multi-drug resistant pathogens, including betalactam, aminoglycosides, chloramphenicol and multi-drug resistances, etc. Both air pollutants and meteorological conditions contributed to the seasonal variation of airborne pathogenic bacteria (r = 0.15, p < 0.01), especially CO, O3, PM2.5, temperature and relative humidity. This study furthers our understanding of airborne pathogens and highlights their associations with ARGs. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota may influence the development of acute pancreatitis (AP), a serious gastrointestinal disease with high morbidity and mortality. This study aimed to identify a causal link by investigating the relationship between gut microbiota and AP. Methods: Mendelian randomization (MR) and a nested case-control study were used to explore associations between gut microbiota composition and AP. 16S rRNA sequencing, random forest modelling (RF), support vector machine (SVM), and Kaplan-Meier survival analysis was applied to identify significant gut microbiota and their correlation with hospitalization duration in AP patients. Results: Bidirectional MR results confirmed a causal link between specific gut microbiota and AP (15 and 8 microbial taxa identified via forward and reverse MR, respectively). The 16S rRNA sequencing analysis demonstrated a pronounced difference in gut microbiota composition between cases and controls. Notably, after a comprehensive evaluation of the results of RF and SVM, Bacteroides plebeius (B. plebeius) was found to play a significant role in influencing the hospital status. Using a receiver operating characteristic (ROC) curve, the predictive power (0.757) of B. plebeius. Kaplan-Meier survival analysis offered further insight that patients with an elevated abundance of B. plebeius experienced prolonged hospital stays. Conclusion: Combining MR with nested case-control studies provided a detailed characterization of interactions between gut microbiota and AP. B. plebeius was identified as a significant contributor, suggesting its role as both a precursor and consequence of AP dynamics. The findings highlight the multifactorial nature of AP and its complex relationship with the gut microbiota. This study lays the groundwork for future therapeutic interventions targeting microbial dynamics in AP treatment. [ABSTRACT FROM AUTHOR]

Background & aims: Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified. Methods: Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs. Results: Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009). Conclusions: Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition. [ABSTRACT FROM AUTHOR]

Simple Summary: Simmental cattle is a renowned breed that is extensively raised because of its high beef and milk fat content. The early establishment of the gut microbiota is closely related to the gut health of calves. However, the structure and function of the gut microbiota in Simmental calves before weaning remain unclear. The development of gut microbiota in neonatal calves is a multifaceted process affected by numerous factors. Gastrointestinal microbiota profoundly affect animal health, productivity, and disease susceptibility, necessitating further study of specific microbial functions during early development. Diarrhea stands out as the most prevalent ailment among lactating calves. Changes in the structure and functionality of the gut microbiota can precipitate gut disorders, ultimately leading to diarrhea. Therefore, thorough investigations of the early colonization patterns of Simmental calves, along with an understanding of the gut microbiota in healthy calves versus those afflicted by diarrhea, have significant implications for diarrhea prevention and development of probiotic interventions. The objective of this study was to explore the dynamic changes in the gut microbiota of Simmental calves before weaning and to compare the microbial composition and functionality between healthy calves and those with diarrhea. Fourteen neonatal Simmental calves were divided into a healthy group (n = 8) and a diarrhea group (n = 6). Rectal stool samples were collected from each calf on days 1, 3, 5, 7, 9, 12, 15, 18, 22, 26, 30, 35, and 40. High-throughput sequencing of the 16S rRNA gene V1–V9 region was conducted to examine changes in the gut microbiota over time in both groups and to assess the influence of diarrhea on microbiota structure and function. Escherichia coli, Bacteroides fragilis, and B. vulgatus were the top three bacterial species in preweaning Simmental calves. Meanwhile, the major functions of the fecal microbiota included "metabolic pathways", "biosynthesis of secondary metabolites", "biosynthesis of antibiotics", "microbial metabolism in diverse environments", and "biosynthesis of amino acids". For calves in the healthy group, PCoA revealed that the bacterial profiles on days 1, 3, 5, 7, and 9 differed from those on days 15, 18, 22, 26, 30, 35, and 40. The profiles on day 12 clustered with both groups, indicating that microbial structure changes increased with age. When comparing the relative abundance of bacteria between healthy and diarrheic calves, the beneficial Lactobacillus johnsonii, Faecalibacterium prausnitzii, and Limosilactobacillus were significantly more abundant in the healthy group than those in the diarrhea group (p < 0.05). This study provides fundamental insights into the gut microbiota composition of Simmental calves before weaning, potentially facilitating early interventions for calf diarrhea and probiotic development. [ABSTRACT FROM AUTHOR]

Background: Obesity is closely associated with lipid accumulation, inflammation and intestinal microbiota dysbiosis. Short‐ and long‐chain type structured lipids (SLCTs) are kinds of low‐calorie structured lipids and demonstrate anti‐obesity and hypolipidemia bioactivity. The objective of this study is to investigate the potential effects of dietary supplementation of SLCTs rich in short‐chain fatty acids and polyunsaturated fatty acids on high‐fat‐diet‐induced obesity and gut microbiota modulation in C57BL/6J mice. Results: Results showed that SLCTs supplementation ameliorated body weight, dyslipidemia, liver lipid accumulation, liver injury and systemic inflammation in obese mice. As expected, immunohistochemical analysis showed that SLCTs significantly increased the expression of proliferator‐activated receptor alpha and decreased the expression of Toll‐like receptor 4 in liver tissue. Furthermore, SLCTs supplementation significantly downregulated the expression level of liver inflammation‐related genes while upregulating the expression level of liver lipid metabolism‐related genes. Additionally, SLCTs supplementation markedly enhanced the diversity of gut microbiota, reduced the Firmicutes/Bacteroidetes ratio and increased the diversity and richness of beneficial intestinal microorganisms, such as Bacteroides, Lactobacillus, Lachnospiraceae NK4A136 group, Alloprevotella and Ruminococcaceae UCG‐014. Conclusion: Our work suggested that SLCTs may have the potential to reduce obesity associated with a high‐fat diet by regulating liver metabolism, inflammation and gut microbiota. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background Bacteroides fragilis , an anaerobic gut bacterium and opportunistic pathogen, comprises two genetically divergent groups (or divisions) at the species level. Differences exist both in the core and accessory genomes and the beta-lactamase genes, with the cephalosporinase gene cep A represented only in division I and the carbapenemase gene cfi A only in division II. Methods Multidrug resistance in a clinical B. fragilis strain was examined by whole-genome sequencing. Results Strain CNM20200260 carried the antimicrobial resistance genes cep A, cfi A2, ant (6'), erm (F), mef (En2), est (T), tet (Q) and cat (A), along with 82-Phe mutation in gyr A (together with 47 amino acid changes in gyr A/B and par C/parE). bex A/B and other efflux pump genes were also observed. None of the detected insertion sequences was located upstream of cfi A2. The genome-based taxonomy coefficients (average nucleotide identity, DNA–DNA hybridization similarity and difference in genomic G + C%) with respect to genomes of the strains of B. fragilis division II and the novel species Bacteroides hominis (both cfi A-positive) met the criteria for CNM20200260 to belong to either species (>95%, >70% and <1%, respectively). No such similarity was seen with type strain NCTC 9343 or the representative genome FDAARGOS 1225 of B. fragilis (division I, cfi A-negative). Strain CNM20200260 harboured four out of nine Kyoto Encyclopedia of Genes and Genomes orthologues defined for division I and one of two defined for division II. Conclusions This is the first description of the co-occurrence of cep A and cfi A in a Bacteroides strain, confirming the complexity of the taxonomy of this species. [ABSTRACT FROM AUTHOR]

Introduction: The gut microbiota and the microbiota-gut-brain axis have gained considerable attention in recent years, emerging as key players in the mechanisms that mediate the occurrence and progression of many central nervous system-related diseases, including epilepsy. In clinical practice, one of the side effects of quinolone antibiotics is a lower seizure threshold or aggravation. However, the underlying mechanism remains unclear. Methods: We aimed to unravel the intrinsic mechanisms through 16S rRNA sequencing and serum untargeted metabolomic analysis to shed light on the effects of gut microbiota in ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. Results: We observed that ciprofloxacin treatment increased seizure susceptibility and caused gut dysbiosis. We also found similar changes in the gut microbiota of rats with lithium pilocarpine-induced epilepsy. Notably, the levels of Akkermansia and Bacteroides significantly increased in both the ciprofloxacin-induced seizure susceptibility and lithium pilocarpine-induced epilepsy rat models. However, Marvinbryantia, Oscillibacter, and Ruminococcaceae_NK4A214_group showed a coincidental reduction. Additionally, the serum untargeted metabolomic analysis revealed decreased levels of indole-3-propionic acid, a product of tryptophan-indole metabolism, after ciprofloxacin treatment, similar to those in the plasma of lithium pilocarpine-induced epilepsy in rats. Importantly, alterations in the gut microbiota, seizure susceptibility, and indole-3-propionic acid levels can be restored by fecal microbiota transplantation. Conclusion: In summary, our findings provide evidence that ciprofloxacin-induced seizure susceptibility is partially mediated by the gut microbiota and tryptophan-indole metabolism. These associations may play a role in epileptogenesis, and impacting the development progression and treatment outcomes of epilepsy. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis‐associated interstitial lung disease (RA‐ILD) is a serious and common extra‐articular disease manifestation. Patients with RA‐ILD experience reduced bacterial diversity and gut bacteriome alterations. However, the gut mycobiome and virome in these patients have been largely neglected. In this study, we performed whole‐metagenome shotgun sequencing on fecal samples from 30 patients with RA‐ILD, and 30 with RA‐non‐ILD, and 40 matched healthy controls. The gut bacteriome and mycobiome were explored using a reference‐based approach, while the gut virome was profiled based on a nonredundant viral operational taxonomic unit (vOTU) catalog. The results revealed significant alterations in the gut microbiomes of both RA‐ILD and RA‐non‐ILD groups compared with healthy controls. These alterations encompassed changes in the relative abundances of 351 bacterial species, 65 fungal species, and 4,367 vOTUs. Bacteria such as Bifidobacterium longum, Dorea formicigenerans, and Collinsella aerofaciens were enriched in both patient groups. Ruminococcus gnavus (RA‐ILD), Gemmiger formicilis, and Ruminococcus bromii (RA‐non‐ILD) were uniquely enriched. Conversely, Faecalibacterium prausnitzii, Bacteroides spp., and Roseburia inulinivorans showed depletion in both patient groups. Mycobiome analysis revealed depletion of certain fungi, including Saccharomyces cerevisiae and Candida albicans, in patients with RA compared with healthy subjects. Notably, gut virome alterations were characterized by an increase in Siphoviridae and a decrease in Myoviridae, Microviridae, and Autographiviridae in both patient groups. Hence, multikingdom gut microbial signatures showed promise as diagnostic indicators for both RA‐ILD and RA‐non‐ILD. Overall, this study provides comprehensive insights into the fecal virome, bacteriome, and mycobiome landscapes of RA‐ILD and RA‐non‐ILD gut microbiota, thereby offering potential biomarkers for further mechanistic and clinical research. [ABSTRACT FROM AUTHOR]

The study was conducted to identify cluster patterns of enteric microorganisms with potential etiological relevance for infectious gastroenteritis in stool samples of individuals from Ghana, which is a known high-endemicity setting for infectious gastroenteritis. These patterns were compared to previous observations with specimens from Colombian indigenous people in order to assess potentially stable clustering for temporally and spatially distinct populations from high-endemicity regions. By doing so, the study aimed to identify stable clusters as markers of microbial interaction with potential importance for etiological relevance assignment in cases of multiple enteric pathogen detections. Stool samples from 1569 Ghanaian individuals (875 from HIV patients, 30 from HIV-negative control adult patients, and 644 from children < 2 years of age) were assessed for enteric microorganisms by applying real-time PCR. As a result, nucleic acids of bacterial microorganisms were most frequently detected, followed by protozoa, microsporidia, and helminths. Interestingly, the cluster assessment confirmed interaction patterns known from the previous analysis with Colombian indigenous people, demonstrating a high likelihood of Blastocystis hominis for clustering with other microorganisms and a prominent, potentially mediating role of Dientamoeba fragilis for microbial interactions within the clusters. In conclusion, the assessment confirmed conserved clustering of enteric microorganisms with potential etiological relevance for human infectious gastroenteritis over geographically distinct high-endemicity settings. Furthermore, the composition of abundant microorganisms is more important than regional factors for the determination of the interplay of enteric microorganisms in the human gut. Thereby, some microbial pathogens and commensals seem more susceptible to a changing microbial composition in the human gut than others. [ABSTRACT FROM AUTHOR]

Lepidoptera, the most diverse group of insects, exhibit female heterogamy (Z0 or ZW), which is different from most other insects (male heterogamy, XY). Previous studies suggest a single origin of the Z chromosome. However, the origin of the lepidopteran W chromosome remains poorly understood. Here, we assemble the genome from females down to the chromosome level of a model insect (Bombyx mori) and identify a W chromosome of approximately 10.1 megabase using a newly developed tool. In addition, we identify 3593 genes that were not previously annotated in the genomes of B. mori. Comparisons of 21 lepidopteran species (including 17 ZW and four Z0 systems) and three trichopteran species (Z0 system) reveal that the formation of Ditrysia W involves multiple mechanisms, including previously proposed canonical and noncanonical models, as well as a newly proposed mechanism called single-Z turnover. We conclude that there are multiple independent origins of the W chromosome in the Ditrysia (most moths and all butterflies) of Lepidoptera. [ABSTRACT FROM AUTHOR]

Microbiome research has gained much attention in recent years as the importance of gut microbiota in regulating host health becomes increasingly evident. However, the impact of radiation on the microbiota in the murine bone marrow transplantation model is still poorly understood. In this paper, we present key findings from our study on how radiation, followed by bone marrow transplantation with or without T cell depletion, impacts the microbiota in the ileum and caecum. Our findings show that radiation has different effects on the microbiota of the two intestinal regions, with the caecum showing increased interindividual variation, suggesting an impaired ability of the host to regulate microbial symbionts, consistent with the Anna Karenina principle. Additionally, we observed changes in the ileum composition, including an increase in bacterial taxa that are important modulators of host health, such as Akkermansia and Faecalibaculum. In contrast, radiation in the caecum was associated with an increased abundance of several common commensal taxa in the gut, including Lachnospiraceae and Bacteroides. Finally, we found that high doses of radiation had more substantial effects on the caecal microbiota of the T-cell-depleted group than that of the non-T-cell-depleted group. Overall, our results contribute to a better understanding of the complex relationship between radiation and the gut microbiota in the context of bone marrow transplantation and highlight the importance of considering different intestinal regions when studying microbiome responses to environmental stressors. [ABSTRACT FROM AUTHOR]

Introduction: Emerging evidence suggests that the gut microbiota is closely associated with bone homeostasis. However, little is known about the relationships among the bone mineral density (BMD) index, bone turnover markers, and the gut microbiota and its metabolites in postmenopausal women. Methods: In this study, to understand gut microbiota signatures and serum metabolite changes in postmenopausal women with reduced BMD, postmenopausal individuals with normal or reduced BMD were recruited and divided into normal and OS groups. Feces and serum samples were collected for 16S rRNA gene sequencing, liquid chromatography coupled with mass spectrometry (LC-MS)-based metabolomics and integrated analysis. Results: The results demonstrated that bacterial richness and diversity were greater in the OS group than in the normal group. Additionally, distinguishing bacteria were found among the two groups and were closely associated with the BMD index and bone turnover markers. Metabolomic analysis revealed that the expression of serum metabolites, such as etiocholanolone, testosterone sulfate, and indole-3-pyruvic acid, and the corresponding signaling pathways, especially those involved in tryptophan metabolism, fatty acid degradation and steroid hormone biosynthesis, also changed significantly. Correlation analysis revealed positive associations between normal group-enriched Bacteroides abundance and normal group-enriched etiocholanolone and testosterone sulfate abundances; in particular, Bacteroides correlated positively with BMD. Importantly, the tryptophan-indole metabolism pathway was uniquely metabolized by the gut bacteria-derived tnaA gene, the predicted abundance of which was significantly greater in the normal group than in the control group, and the abundance of Bacteroides was strongly correlated with the tnaA gene. Discussion: Our results indicated a clear difference in the gut microbiota and serum metabolites of postmenopausal women. Specifically altered bacteria and derived metabolites were closely associated with the BMD index and bone turnover markers, indicating the potential of the gut microbiota and serum metabolites as modifiable factors and therapeutic targets for preventing osteoporosis. [ABSTRACT FROM AUTHOR]

Background: The interplay between gut microbiota and metabolites in the early stages of sepsis-induced acute kidney injury (SA-AKI) is not yet clearly understood. This study explores the characteristics and interactions of gut microbiota, and blood and urinary metabolites in patients with SA-AKI. Methods: Utilizing a prospective observational approach, we conducted comparative analyses of gut microbiota and metabolites via metabolomics and metagenomics in individuals diagnosed with SA-AKI compared to those without AKI (NCT06197828). Pearson correlations were used to identify associations between microbiota, metabolites, and clinical indicators. The Comprehensive Antibiotic Resistance Database was employed to detect antibiotic resistance genes (ARGs), while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways informed on metabolic processes and microbial resistance patterns. Results: Our study included analysis of four patients with SA-AKI and five without AKI. Significant disparities in bacterial composition were observed, illustrated by diversity indices (Shannon index: 2.0 ± 0.4 vs. 1.4 ± 0.6, P = 0.230; Simpson index: 0.8 ± 0.1 vs. 0.6 ± 0.2, P = 0.494) between the SA-AKI group and the non-AKI group. N6, N6, N6-Trimethyl-L-lysine was detected in both blood and urine metabolites, and also showed significant correlations with specific gut microbiota (Campylobacter hominis and Bacteroides caccae, R > 0, P < 0.05). Both blood and urine metabolites were enriched in the lysine degradation pathway. We also identified the citrate cycle (TCA cycle) as a KEGG pathway enriched in sets of differentially expressed ARGs in the gut microbiota, which exhibits an association with lysine degradation. Conclusions: Significant differences in gut microbiota and metabolites were observed between the SA-AKI and non-AKI groups, uncovering potential biomarkers and metabolic changes linked to SA-AKI. The lysine degradation pathway may serve as a crucial link connecting gut microbiota and metabolites. [ABSTRACT FROM AUTHOR]