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Engineering the genetic code of an organism provides the basis for (i) making any organism safely resistant to natural viruses and (ii) preventing genetic information flow into and out of genetically modified organisms while (iii) allowing the biosynthesis of genetically encoded unnatural polymers1-4. Achieving these three goals requires the reassignment of multiple of the 64 codons nature uses to encode proteins. However, synonymous codon replacement-recoding-is frequently lethal, and how recoding impacts fitness remains poorly explored. Here, we explore these effects using whole-genome synthesis, multiplexed directed evolution, and genome-transcriptome-translatome-proteome co-profiling on multiple recoded genomes. Using this information, we assemble a synthetic Escherichia coli genome in seven sections using only 57 codons to encode proteins. By discovering the rules responsible for the lethality of synonymous recoding and developing a data-driven multi-omics-based genome construction workflow that troubleshoots synthetic genomes, we overcome the lethal effects of 62,007 synonymous codon swaps and 11,108 additional genomic edits. We show that synonymous recoding induces transcriptional noise including new antisense RNAs, leading to drastic transcriptome and proteome perturbation. As the elimination of select codons from an organism's genetic code results in the widespread appearance of cryptic promoters, we show that synonymous codon choice may naturally evolve to minimize transcriptional noise. Our work provides the first genome-scale description of how synonymous codon changes influence organismal fitness and paves the way for the construction of functional genomes that provide genetic firewalls from natural ecosystems and safely produce biopolymers, drugs, and enzymes with an expanded chemistry.
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AIMS: Little is known about the molecular features of visible polyps with low-grade intestinal-type dysplasia in patients with inflammatory bowel disease (IBD). To better understand their origins and biological potential, we sought to genomically profile these lesions and compare them with invisible low-grade dysplasia and sporadic adenomas from non-IBD patients. METHODS: 22 polyps within areas of colitis, 13 polyps outside areas of colitis, 10 foci of invisible dysplasia from patients with IBD and 6 sporadic tubular adenomas from non-IBD patients were analysed using the OncoPanel assay. RESULTS: Polyps arising in areas of colitis showed a greater spectrum of mutations, including APC, KRAS, FBXW7, TP53, ARID1A and TCF7L2. Polyps outside colitis and non-IBD sporadic adenomas showed a limited mutational profile, with APC and CTNNB1 mutations. Invisible dysplasia was characterised by TP53, CTNNB1 and KRAS alterations. Compared with dysplastic polyps, none of the invisible dysplastic foci showed APC alterations (73%-within colitis; p=0.0001, 92%-outside colitis; p<0.0001, 83%-sporadic adenomas; p=0.001). TP53 mutations were significantly higher in invisible dysplasia (50%) compared with polyps within colitis (9%; p=0.02) and outside colitis (8%; p=0.03). CONCLUSIONS: Molecular alterations in visible low-grade dysplastic polyps with conventional intestinal-type dysplasia from patients with IBD and sporadic adenomas from non-IBD patients overlap significantly. APC alterations appear to play a major role in the development of visible low-grade dysplastic lesions in patients with IBD, regardless of background colitis. As with IBD-associated colorectal cancers, TP53 mutations are an early event in the development of invisible, low-grade conventional intestinal-type dysplasia in patients with IBD.
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Mast cell activation syndrome (MCAS) is a term applied to several clinical entities that have gained increased attention from patients and medical providers. Although several descriptive publications about MCAS exist, there are many gaps in knowledge, resulting in confusion about this clinical syndrome. Whether MCAS is a primary syndrome or exists as a constellation of symptoms in the context of known inflammatory, allergic, or clonal disorders associated with systemic mast cell activation is not well understood. More importantly, the underlying mechanisms and pathways that lead to mast cell activation in MCAS patients remain to be elucidated. Here we summarize the known literature, identify gaps in knowledge, and highlight research needs. Covered topics include contextualization of MCAS and MCAS-like endotypes and related diagnostic evaluations; mechanistic research; management of typical and refractory symptoms; and MCAS-specific education for patients and health care providers.
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Mastócitos , Mastocitose , Humanos , Mastócitos/imunologia , Mastocitose/diagnóstico , Mastocitose/imunologia , Síndrome , AnimaisRESUMO
Current approaches to diagnosing male infertility inadequately assess the complexity of the male gamete. Beyond the paternal haploid genome, spermatozoa also deliver coding and non-coding RNAs to the oocyte. While sperm-borne RNAs have demonstrated potential involvement in embryo development, the underlying mechanisms remain unclear. In this study, 47 sperm samples from normozoospermic males undergoing fertility treatment using donor oocytes were sequenced and analyzed to evaluate associations between sperm RNA elements (exon-sized sequences) and blastocyst progression. A total of 366 RNA elements (REs) were significantly associated with blastocyst rate (padj < 0.05), some of which were linked to genes related to critical developmental processes, including mitotic spindle formation and both ectoderm and mesoderm specification. Of note, 27 RE-associated RNAs are predicted targets of our previously reported list of developmentally significant miRNAs. Inverse RE-miRNA expression patterns were consistent with miRNA-mediated down-regulation. This study provides a comprehensive set of REs which differ by the patient's ability to produce blastocysts. This knowledge can be leveraged to improve clinical screening of male infertility and ultimately reduce time to pregnancy.
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Infertilidade Masculina , MicroRNAs , Espermatozoides , Humanos , Masculino , Infertilidade Masculina/genética , Espermatozoides/metabolismo , MicroRNAs/genética , Adulto , Feminino , Blastocisto/metabolismo , RNA/genética , RNA/metabolismo , Desenvolvimento Embrionário/genéticaRESUMO
Perfluorooctanesulfonic acid (PFOS) is detected in estuarine environments, where salinity levels fluctuate regularly. We investigated the effects of salinity on the toxicity of PFOS in embryos and larvae of Cyprinodon variegatus. We crossed six PFOS treatments (0, 1-10,000 µg/L) with two salinities (10, 30 ppt). Larvae exposed to the highest concentration of PFOS under high salinity accumulated over twice the amount of PFOS compared to larvae maintained under low salinity. Embryonic survival was unaffected by PFOS, salinity, or their interaction. PFOS delayed time to hatch and increased salinity reduced time to hatch regardless of PFOS treatment; however, no salinity by PFOS interactions were observed. Conversely, PFOS and salinity interacted in the larval stage, with decreased survival at 30 ppt salinity. This is one of the first studies evaluating interactive effects of PFOS and high salinity and highlights the importance of assessing PFAS toxicity across life stages.
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Ácidos Alcanossulfônicos , Fluorocarbonos , Larva , Salinidade , Poluentes Químicos da Água , Animais , Fluorocarbonos/toxicidade , Ácidos Alcanossulfônicos/toxicidade , Poluentes Químicos da Água/toxicidade , Larva/efeitos dos fármacos , Estuários , Peixes Listrados/fisiologia , Embrião não Mamífero/efeitos dos fármacosRESUMO
We are developing an economic model to explore multiple topics in Australian youth mental health policy. To help make that model more readily transferable to other jurisdictions, we developed a software framework for authoring modular computational health economic models (CHEMs) (the software files that implement health economic models). We specified framework user requirements for: a simple programming syntax; a template CHEM module; tools for authoring new CHEM modules; search tools for finding existing CHEM modules; tools for supplying CHEM modules with data; reproducible analysis and reporting tools; and tools to help maintain a CHEM project website. We implemented the framework as six development version code libraries in the programming language R that integrate with online services for software development and research data archiving. We used the framework to author five development version R libraries of CHEM modules focussed on utility mapping in youth mental health. These modules provide tools for variable validation, dataset description, multi-attribute instrument scoring, construction of mapping models, reporting of mapping studies and making out of sample predictions. We assessed these CHEM module libraries as mostly meeting transparency, reusability and updatability criteria that we have previously developed, but requiring more detailed documentation and unit testing of individual modules. Our software framework has potential value as a prototype for future tools to support the development of transferable CHEMs.Code: Visit https://www.ready4-dev.com for more information about how to find, install and apply the prototype software framework.
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Saúde Mental , Modelos Econômicos , Software , Humanos , Adolescente , Austrália , Serviços de Saúde Mental/economia , Serviços de Saúde Mental/organização & administração , Política de SaúdeRESUMO
Crohn's disease (CD) is often treated with either exclusive or supplemental enteral nutrition (EN) in pediatrics, but adult practice guidelines primarily focus on medications. Here, we demonstrate the feasibility of a 4-week semi-elemental-formula-based oral nutrition delivery program for managing adult CD (n = 4). Patients consumed ~66% of calories from the formula, a finding that might provide an improved calorie target for future trials. We identified Flavinofractor as the only differentially abundant genus, distinguishing post-intervention samples from pre-intervention samples. Findings from this pilot trial demonstrate the feasibility of a partial enteral nutrition protocol in adult CD management and contribute to the growing body of literature on the potential role of EN therapy in adults with CD.
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INTRODUCTION: The optimal proton pump inhibitor (PPI) regimen for eosinophilic esophagitis (EoE) is unclear. We compared histologic response rates of different dosing combinations. METHODS: A total of 305 patients with newly diagnosed EoE received standard (omeprazole 20 mg daily), once-daily moderate (40 mg daily), twice-daily moderate (20 mg twice daily), or high (40 mg twice daily) dose PPI for ≥8 weeks. RESULTS: Approximately 42.3% achieved histologic response to PPI, with higher rates for twice-daily (moderate 52.8%/high 54.3%) than once-daily (standard 11.8%/moderate 10%) dosing ( P < 0.0001). On multivariable analysis, twice-daily moderate (adjusted odds ratio 6.75, confidence interval 2.53-18.0, P = 0.0008) and high (adjusted odds ratio 12.8, confidence interval 4.69-34.8, P < 0.0001) doses independently predicted histologic response. DISCUSSION: Twice-daily PPI is associated with higher EoE histologic response rates than once-daily regimen.
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Esquema de Medicação , Esofagite Eosinofílica , Inibidores da Bomba de Prótons , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/patologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Omeprazol/administração & dosagem , Resultado do Tratamento , Indução de Remissão , Adulto Jovem , Relação Dose-Resposta a DrogaRESUMO
OBJECTIVE: Falls in older adults correlate with heightened morbidity and mortality. Assessing fall risk in the emergency department (ED) not only aids in identifying candidates for prevention interventions but may also offer insights into overall mortality risk. We sought to examine the link between fall risk and 30-day mortality in older ED adults. METHODS: Observational cohort study of adults aged ≥ 75years who presented to an academic ED and who were assessed for fall risk using the Memorial Emergency Department Fall Risk Assessment Tool (MEDFRAT), a validated, ED-specific screening tool. The fall risk was classified as low (0-2 points), moderate (3-4 points), or high (≥5) risk. The primary outcome was 30-day mortality. Hazard ratios (HR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 941 patients whose fall risk was assessed in the ED were included in the study. Median age was 83.7 years; 45.6% were male, 75.6% lived in private residences, and 62.7% were admitted. Mortality at 30 days among the high fall risk group was four times that of the low fall risk group (11.8% vs 3.1%; HR 4.00, 95% CI 2.18 to 7.34, p < 0.001). Moderate fall risk individuals had nearly double the mortality rate of the low-risk group (6.0% vs 3.1%), but the difference was not statistically significant (HR 1.98, 95% CI 0.91 to 4.32, p = 0.087). CONCLUSION: ED fall risk assessments are linked to 30-day mortality. Screening may facilitate the stratification of older adults at risk for health deterioration.
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Acidentes por Quedas , Serviço Hospitalar de Emergência , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Acidentes por Quedas/prevenção & controle , Fatores de Risco , Medição de Risco , HospitalizaçãoRESUMO
In 9 patients hospitalized for acute severe ulcerative colitis, 8 were successfully discharged without the need for colectomy. Six of 7 patients with sufficient follow-up achieved steroid-free clinical remission at 8 to 16 weeks, and 1 of 2 patients achieved endoscopic response.
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Colite Ulcerativa , Compostos Heterocíclicos com 3 Anéis , Humanos , Colite Ulcerativa/tratamento farmacológico , Masculino , Feminino , Adulto , Estados Unidos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Pessoa de Meia-Idade , Resultado do Tratamento , Índice de Gravidade de Doença , Doença AgudaRESUMO
Perfluorooctanesulfonate (PFOS) is a widespread environmental pollutant with a long half-life and clearly negative outcomes on metabolic diseases such as fatty liver disease and diabetes. Male and female Cyp2b-null and humanized CYP2B6-transgenic (hCYP2B6-Tg) mice were treated with 0, 1, or 10 mg/kg/day PFOS for 21 days, and surprisingly it was found that PFOS was retained at greater concentrations in the serum and liver of hCYP2B6-Tg mice than those of Cyp2b-null mice, with greater differences in the females. Thus, Cyp2b-null and hCYP2B6-Tg mice provide new models for investigating individual mechanisms for PFOS bioaccumulation and toxicity. Overt toxicity was greater in hCYP2B6-Tg mice (especially females) as measured by mortality; however, steatosis occurred more readily in Cyp2b-null mice despite the lower PFOS liver concentrations. Targeted lipidomics and transcriptomics from PFOS-treated Cyp2b-null and hCYP2B6-Tg mouse livers were performed and compared to PFOS retention and serum markers of toxicity using PCA. Several oxylipins, including prostaglandins, thromboxanes, and docosahexaenoic acid metabolites, are associated or inversely associated with PFOS toxicity. Both lipidomics and transcriptomics indicate PFOS toxicity is associated with PPAR activity in all models. GO terms associated with reduced steatosis were sexually dimorphic with lipid metabolism and transport increased in females and circadian rhythm associated genes increased in males. However, we cannot rule out that steatosis was initially protective from PFOS toxicity. Moreover, several transporters are associated with increased retention, probably due to increased uptake. The strongest associations are the organic anion transport proteins (Oatp1a4-6) genes and a long-chain fatty acid transport protein (fatp1), enriched in female hCYP2B6-Tg mice. PFOS uptake was also reduced in cultured murine hepatocytes by OATP inhibitors. The role of OATP1A6 and FATP1 in PFOS transport has not been tested. In summary, Cyp2b-null and hCYP2B6-Tg mice provided unique models for estimating the importance of novel mechanisms in PFOS retention and toxicity.
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PURPOSE OF REVIEW: Mast cell activation syndrome (MCAS) is a clinical disorder that may explain irritable bowel syndrome (IBS) type symptoms as well as other allergic symptoms experienced by an individual. The diagnosis and treatment of MCAS with specific focus on gastrointestinal (GI) manifestations is reviewed. RECENT FINDINGS: Although biomarkers for MCAS remain elusive, testing for baseline serum tryptase will distinguish the type of mast cell disorder and urine tests for mast cell mediator metabolites may support the diagnosis. Endoscopy and Colonoscopy with biopsies is not used to diagnose MCAS but is important to rule out other conditions that may cause symptoms. There is increased awareness of the association between MCAS and autonomic dysfunction, small fiber neuropathy, and connective tissue disorders which all impact GI symptoms. MCAS is a disorder often of unknown etiology (idiopathic) and characterized by intermittent allergy type symptoms that affect multiple organ systems after exposure to a trigger. GI symptoms including abdominal cramping and loose stool are prominent and mimic those of IBS. Diagnostic testing is performed to assess for elevations in mast cell mediators during symptoms and to rule out other conditions. A comprehensive treatment plan includes medications that target mast cells, treatments for associated conditions including autonomic dysfunction, and management of comorbid psychiatric illness and nutritional deficits.
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Gastroenteropatias , Síndrome do Intestino Irritável , Síndrome da Ativação de Mastócitos , Mastocitose , Humanos , Mastocitose/complicações , Mastocitose/diagnóstico , Mastocitose/terapia , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Síndrome do Intestino Irritável/terapia , Mastócitos/patologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/etiologia , Gastroenteropatias/terapiaRESUMO
Autonomic symptom questionnaires are frequently used to assess dysautonomia. It is unknown whether subjective dysautonomia obtained from autonomic questionnaires correlates with objective dysautonomia measured by quantitative autonomic testing. The objective of our study was to determine correlations between subjective and objective measures of dysautonomia. This was a retrospective cross-sectional study conducted at Brigham and Women's Faulkner Hospital Autonomic Laboratory between 2017 and 2023 evaluating the patients who completed autonomic testing. Analyses included validated autonomic questionnaires [Survey of Autonomic Symptoms (SAS), Composite Autonomic Symptom Score 31 (Compass-31)] and standardized autonomic tests (Valsalva maneuver, deep breathing, sudomotor, and tilt test). The autonomic testing results were graded by a Quantitative scale for grading of cardiovascular reflexes, sudomotor tests and skin biopsies (QASAT), and Composite Autonomic Severity Score (CASS). Autonomic testing, QASAT, CASS, and SAS were obtained in 2627 patients, and Compass-31 in 564 patients. The correlation was strong between subjective instruments (SAS vs. Compass-31, r = 0.74, p < 0.001) and between objective instruments (QASAT vs. CASS, r = 0.81, p < 0.001). There were no correlations between SAS and QASAT nor between Compass-31 and CASS. There continued to be no correlations between subjective and objective instruments for selected diagnoses (post-acute sequelae of COVID-19, n = 61; postural tachycardia syndrome, 211; peripheral autonomic neuropathy, 463; myalgic encephalomyelitis/chronic fatigue syndrome, 95; preload failure, 120; post-treatment Lyme disease syndrome, 163; hypermobile Ehlers-Danlos syndrome, 213; neurogenic orthostatic hypotension, 86; diabetes type II, 71, mast cell activation syndrome, 172; hereditary alpha tryptasemia, 45). The lack of correlation between subjective and objective instruments highlights the limitations of the commonly used questionnaires with some patients overestimating and some underestimating true autonomic deficit. The diagnosis-independent subjective-objective mismatch further signifies the unmet need for reliable screening surveys. Patients who overestimate the symptom burden may represent a population with idiosyncratic autonomic-like symptomatology, which needs further study. At this time, the use of autonomic questionnaires as a replacement of autonomic testing cannot be recommended.
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Ácido Penicilânico/análogos & derivados , Síndrome da Taquicardia Postural Ortostática , Humanos , Feminino , Estudos Retrospectivos , Estudos Transversais , Inquéritos e QuestionáriosRESUMO
Legacy polyfluoroalkyl substances (PFAS) [perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA)] are being replaced by various other fluorinated compounds, such as hexafluoropropylene oxide dimer acid (GenX). These alternatives are thought to be less bioaccumulative and, therefore, less toxic than legacy PFAS. Contaminant exposures occur concurrently with exposure to natural stressors, including the fungal pathogen Batrachocytrium dendrobatidis (Bd). Despite evidence that other pollutants can increase the adverse effects of Bd on anurans, no studies have examined the interactive effects of Bd and PFAS. This study tested the growth and developmental effects of PFOS, PFOA, and GenX on gray treefrog (Hyla versicolor) tadpoles, followed by a Bd challenge after metamorphosis. Despite PFAS exposure only occurring during the larval stage, carry-over effects on growth were observed post metamorphosis. Further, PFAS interacted with Bd exposure to influence growth; Bd-exposed animals had significantly shorter SVL [snout-vent length (mm)] with significantly increased body condition, among other time-dependent effects. Our data suggest that larval exposure to PFAS can continue to impact growth in the juvenile stage after exposure has ended. Contrary to predictions, GenX affected terrestrial performance more consistently than its legacy congener, PFOA. Given the role of Bd in amphibian declines, further investigation of interactions of PFAS with Bd and other environmentally relevant pathogens is warranted.
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Ácidos Alcanossulfônicos , Fluorocarbonos , Animais , Larva/microbiologia , Fluorocarbonos/toxicidade , Anuros/microbiologia , Ácidos Alcanossulfônicos/toxicidadeRESUMO
Background and Aims: The management of post-operative pain after surgical repair of pectus excavatum with the Ravitch procedure is challenging. Although previous studies have compared various methods of pain control in these patients, few have compared different local anesthetics. This retrospective analysis compares the use of bupivacaine to its longer-acting form, liposomal bupivacaine, in patients who had undergone pectus excavatum repair with the Ravitch method. Material and Methods: Eleven patients who received local infiltration with liposomal bupivacaine were matched to 11 patients who received local infiltration utilizing bupivacaine with epinephrine. The primary outcome was total morphine milligram equivalents per kilogram body weight (MME/kg) over the complete length of hospital stay. Secondary outcomes included total cumulative diazepam, acetaminophen, ondansetron, and NSAID dose per kilogram body weight (mg/kg) over the course of the hospital stay, chest tube drainage (ml/kg body weight), number of post-operative hours until the first bowel movement, Haller Index, patient request for magnesium hydroxide, average pain scores from post-operative day 1 to post-operative day 5, and length of hospital stay. Continuous variables were reported as medians with inter-quartile ranges, and categorical values were reported as percentages and frequencies. Results: The total MME/kg [1.7 (1.2-2.4) vs 2.9 (2.0-3.9), P = 0.007] and hydromorphone (mg/kg) [0.1 (0.0-0.2) vs 0.3 (0.1-0.4), P = 0.006] use in the liposomal bupivacaine group versus bupivacaine with epinephrine was significantly reduced over total length of hospital stay. Similarly, there was a reduction in diazepam use in the liposomal bupivacaine group versus the bupivacaine group [0.4 (0.1-0.8) vs 0.6 (0.4-0.7), P = 0.249], but this did not reach statistical significance. The total dose of ondansetron (mg/kg) was not statistically different when comparing the liposomal bupivacaine group to the bupivacaine group [0.3 (0.0-0.5) vs 0.3 (0.2-0.6), P = 0.332]. Interestingly, the total dose of acetaminophen (mg/kg) was statistically increased in the liposomal bupivacaine group compared to the bupivacaine with epinephrine group [172 (138-183) vs 74 (55-111), P = 0.007]. Additionally, the total chest tube drainage (ml/kg) was significantly reduced in the liposomal bupivacaine group [9.3 (7.5-10.6) vs 12.8 (11.3-18.5), P = 0.027]. Finally, the percentage of patients without requests for magnesium hydroxide to promote laxation was significantly higher in the liposomal bupivacaine group than in the bupivacaine group (63.6% vs 18.2%, P = 0.027). Conclusion: The use of liposomal bupivacaine for local infiltration in patients who undergo the Ravitch procedure for pectus repair offers advantages over plain bupivacaine, including reduced opioid consumption and opioid-related side effects. However, more data are needed to understand the significance of these findings.
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BACKGROUND: Growing evidence from dogs and humans supports the abundance of mutation-based biomarkers in tumors of dogs. Increasing the use of clinical genomic diagnostic testing now provides another powerful data source for biomarker discovery. HYPOTHESIS: Analyzed clinical outcomes in dogs with cancer profiled using SearchLight DNA, a cancer gene panel for dogs, to identify mutations with prognostic value. ANIMALS: A total of 127 cases of cancer in dogs were analyzed using SearchLight DNA and for which clinical outcome information was available. METHODS: Clinical data points were collected by medical record review. Variables including mutated genes, mutations, signalment, and treatment were fitted using Cox proportional hazard models to identify factors associated with progression-free survival (PFS). The log-rank test was used to compare PFS between patients receiving and not receiving targeted treatment before first progression. RESULTS: Combined genomic and outcomes analysis identified 336 unique mutations in 89 genes across 26 cancer types. Mutations in 6 genes (CCND1, CCND3, SMARCB1, FANCG, CDKN2A/B, and MSH6) were significantly associated with shorter PFS. Dogs that received targeted treatment before first progression (n = 45) experienced significantly longer PFS compared with those that did not (n = 82, P = .01). This significance held true for 29 dogs that received genomically informed targeted treatment compared with those that did not (P = .05). CONCLUSION AND CLINICAL IMPORTANCE: We identified novel mutations with prognostic value and demonstrate the benefit of targeted treatment across multiple cancer types. These results provide clinical evidence of the potential for genomics and precision medicine in dogs with cancer.
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Doenças do Cão , Neoplasias , Humanos , Cães , Animais , Prognóstico , Neoplasias/genética , Neoplasias/veterinária , Intervalo Livre de Progressão , Mutação , Genômica , DNA , Biomarcadores Tumorais/genética , Doenças do Cão/genéticaRESUMO
Fecal microbiota transplantation (FMT) has emerged as a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) and also a potential therapy for other diseases associated with dysbiotic gut microbiota. Monitoring metabolic changes in biofluids and excreta is a noninvasive approach to identify the biomarkers of microbial recolonization and to understand the metabolic influences of FMT on the host. In this study, the pre-FMT and post FMT urine samples from 11 rCDI patients were compared through metabolomic analyses for FMT-induced metabolic changes. The results showed that p-cresol sulfate in urine, a microbial metabolite of tyrosine, was rapidly elevated by FMT and much more responsive than other microbial metabolites of aromatic amino acids (AAAs). Because patients were treated with vancomycin prior to FMT, the influence of vancomycin on the microbial metabolism of AAAs was examined in a mouse feeding trial, in which the decreases in p-cresol sulfate, phenylacetylglycine, and indoxyl sulfate in urine were accompanied with significant increases in their AAA precursors in feces. The inhibitory effects of antibiotics and the recovering effects of FMT on the microbial metabolism of AAAs were further validated in a mouse model of FMT. Overall, urinary p-cresol sulfate may function as a sensitive and convenient therapeutic indicator on the effectiveness of antibiotics and FMT for the desired manipulation of gut microbiota in human patients.