Waterborne Escherichia coli are a major reservoir of antimicrobial resistance (AMR), including but not limited to extended-spectrum beta-lactamase (ESBL) and Klebsiella pneumoniae carbapenemase (KPC) mechanisms. This study quantified and described ESBL- and KPC-producing E. coli in Northern Colorado from sewer water, surface water, and influent and effluent wastewater treatment sources. Total detected bacteria and E. coli abundances, and the percentages that contain ESBL and/or KPC, were compared between water sources. Seventy E. coli isolates from the various waters had drug resistance validated with a panel of 17 antibiotics using a broth microdilution assay. The diverse drug resistance observed across E. coli isolates was further documented by polymerase chain reaction of common ESBL genes and functional relatedness by PhenePlate assay-generated dendrograms (n=70). The total E. coli abundance decreased through the water treatment process as expected, yet the percentages of E. coli harboring ESBL resistance were increased (1.70%) in surface water. Whole-genome sequencing analysis was completed for 185 AMR genes in wastewater E. coli isolates and confirmed the presence of diverse AMR gene classes (e.g., beta-lactams and efflux pumps) in isolate genomes. This study completed surveillance of AMR patterns in E. coli that reside in environmental water systems and suggests a role for integrating both phenotypic and genotypic profiling beyond ESBL and KPC mechanisms. AMR screening via multiple approaches may assist in the prevention of drug-resistant E. coli spread from waters to animals and humans.

Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States and emerging evidence supports that increased consumption of legumes, such as navy beans, can reduce risk. Navy bean consumption was previously shown to modulate host and microbiome metabolism, and this investigation was performed to assess the impact on the human stool metabolome, which includes the presence of navy bean metabolites. This 4-week, randomized-controlled trial with overweight and obese CRC survivors involved consumption of 1 meal and 1 snack daily. The intervention contained 35 g of cooked navy bean or macronutrient matched meals and snacks with 0 g of navy beans for the control group (n = 18). There were 30 statistically significant metabolite differences in the stool of participants that consumed navy bean at day 28 compared to the participants’ baseline (p ≤ 0.05) and 26 significantly different metabolites when compared to the control group. Of the 560 total metabolites identified from the cooked navy beans, there were 237 possible navy bean-derived metabolites that were identified in the stool of participants consuming navy beans, such as N-methylpipecolate, 2-aminoadipate, piperidine, and vanillate. The microbial metabolism of amino acids and fatty acids were also identified in stool after 4 weeks of navy bean intake including cadaverine, hydantoin-5 propionic acid, 4-hydroxyphenylacetate, and caprylate. The stool relative abundance of ophthalmate increased 5.25-fold for navy bean consumers that can indicate glutathione regulation, and involving cancer control mechanisms such as detoxification of xenobiotics, antioxidant defense, proliferation, and apoptosis. Metabolic pathways involving lysine, and phytochemicals were also modulated by navy bean intake in CRC survivors. These metabolites and metabolic pathways represent an acute response to increased navy bean intake, which merit further investigation for improving colonic health after long-term consumption.

Rice bran has bioactive phytochemicals with cancer protective actions that involve metabolism by the host and the gut microbiome. Globally, colorectal cancer (CRC) is the third leading cause of cancer-related death and the increased incidence is largely attributed to poor dietary patterns, including low daily fiber intake. A dietary intervention trial was performed to investigate the impact of rice bran consumption on the plasma and urine metabolome of CRC survivors. Nineteen CRC survivors participated in a randomized-controlled trial that included consumption of heat-stabilized rice bran (30 g/day) or a control diet without rice bran for 4 weeks. A fasting plasma and first void of the morning urine sample were analyzed by non-targeted metabolomics using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). After 4 weeks of either rice bran or control diets, 12 plasma and 16 urine metabolites were significantly different between the groups (p≤0.05). Rice bran intake increased relative abundance of plasma mannose (1.373-fold) and beta-citrylglutamate (BCG) (1.593-fold), as well as increased urine N-formylphenylalanine (2.191-fold) and dehydroisoandrosterone sulfate (DHEA-S) (4.488-fold). Diet affected metabolites, such as benzoate, mannose, eicosapentaenoate (20:5n3) (EPA), and N-formylphenylalanine have been previously reported for cancer protection and were identified from the rice bran food metabolome. Nutritional metabolome changes following increased consumption of whole grains such as rice bran warrants continued investigation for colon cancer control and prevention attributes as dietary biomarkers for positive effects are needed to reduce high risk for colorectal cancer recurrence.

Navy beans contain bioactive phytochemicals with colon cancer prevention properties as demonstrated in carcinogen-induced animal models. Human studies support that dietary navy bean intake modulates metabolism by the gut microbiome. This study investigated the effect of navy bean ingestion on plasma and urine metabolite profiles of overweight and obese colorectal cancer survivors. Twenty participants completed a single-blinded, randomized-controlled dietary intervention with precooked navy beans (35 g bean powder/day) or control (0 g/day) for 4 weeks. Plasma and urine were collected at baseline, 2 weeks, and 4 weeks following consumption. Nontargeted metabolomics was applied to study meals and snacks, navy beans, plasma, and urine. Increased navy bean consumption was hypothesized to (i) delineate dietary biomarkers and (ii) promote metabolic shifts relevant for cancer protection in the plasma and urine metabolome. At 4 weeks, 16 plasma and 16 urine metabolites were significantly different in the navy bean intervention group compared with placebo control (P < 0.05). Increased plasma 2,3-dihydroxy-2-methylbutyrate (1.34-fold), S-methylcysteine (1.92-fold), and pipecolate (3.89-fold), and urine S-adenosylhomocysteine (2.09-fold) and cysteine (1.60-fold) represent metabolites with cancerprotective actions following navy bean consumption. Dietderived metabolites were detected in plasma or urine and confirmed for presence in the navy bean intervention meals and snacks. These included 3-(4-hydroxyphenyl) propionate, betaine, pipecolate, S-methylcysteine, choline, eicosapentaenoate (20:5n3), benzoate, S-adenosylhomocysteine, N-delta-acetylornithine, cysteine, 3-(4-hydroxyphenyl)lactate, gentisate, hippurate, 4-hydroxyhippurate, and salicylate. The navy bean dietary intervention for 4 weeks showed changes to pathways of metabolic importance to colorectal cancer prevention and merit continued attention for dietary modulation in future high-risk cohort investigations.Prevention Relevance: This clinical study suggests that increased consumption of navy beans would deliver bioactive metabolites to individuals at high risk for colorectal cancer recurrence and produce metabolic shifts in plasma and urine profiles.

<div>Abstract<p>Navy beans contain bioactive phytochemicals with colon cancer prevention properties as demonstrated in carcinogen-induced animal models. Human studies support that dietary navy bean intake modulates metabolism by the gut microbiome. This study investigated the effect of navy bean ingestion on plasma and urine metabolite profiles of overweight and obese colorectal cancer survivors. Twenty participants completed a single-blinded, randomized-controlled dietary intervention with precooked navy beans (35 g bean powder/day) or control (0 g/day) for 4 weeks. Plasma and urine were collected at baseline, 2 weeks, and 4 weeks following consumption. Nontargeted metabolomics was applied to study meals and snacks, navy beans, plasma, and urine. Increased navy bean consumption was hypothesized to (i) delineate dietary biomarkers and (ii) promote metabolic shifts relevant for cancer protection in the plasma and urine metabolome. At 4 weeks, 16 plasma and 16 urine metabolites were significantly different in the navy bean intervention group compared with placebo control (<i>P</i> < 0.05). Increased plasma 2,3-dihydroxy-2-methylbutyrate (1.34-fold), S-methylcysteine (1.92-fold), and pipecolate (3.89-fold), and urine S-adenosylhomocysteine (2.09-fold) and cysteine (1.60-fold) represent metabolites with cancer-protective actions following navy bean consumption. Diet-derived metabolites were detected in plasma or urine and confirmed for presence in the navy bean intervention meals and snacks. These included 3-(4-hydroxyphenyl)propionate, betaine, pipecolate, S-methylcysteine, choline, eicosapentaenoate (20:5n3), benzoate, S-adenosylhomocysteine, N-delta-acetylornithine, cysteine, 3-(4-hydroxyphenyl)lactate, gentisate, hippurate, 4-hydroxyhippurate, and salicylate. The navy bean dietary intervention for 4 weeks showed changes to pathways of metabolic importance to colorectal cancer prevention and merit continued attention for dietary modulation in future high-risk cohort investigations.</p>Prevention Relevance:<p>This clinical study suggests that increased consumption of navy beans would deliver bioactive metabolites to individuals at high risk for colorectal cancer recurrence and produce metabolic shifts in plasma and urine profiles.</p></div>