**Background:** High red and processed meat consumption is consistently associated with increased colorectal cancer (CRC) risk, partly through increased faecal genotoxicity and nitroso compound (NOC) excretion. Mycoprotein, a high-fibre meat alternative derived from Fusarium venenatum, has been consumed for decades but its effects on human gut health and CRC risk markers were previously unstudied. This trial aimed to compare the effects of substituting a high meat intake with mycoprotein on biomarkers of CRC risk and gut health.
**Methods:** Mycomeat was a single-site, investigator-blind, randomised crossover trial (NCT03944421) conducted at Northumbria University, UK. Twenty healthy male adults (mean age 30.4 ± 7.92 years, BMI 24.0 ± 2.87 kg/m²) were randomised to consume 240 g/day of red and processed meat or 240 g/day mycoprotein (Quorn™ products) for 2 weeks, separated by a 4-week washout. Primary endpoints were faecal water genotoxicity (CometChip assay in Caco-2 cells) and faecal NOC (chemiluminescence). Secondary endpoints included gut microbiome composition (16S rRNA amplicon sequencing), faecal short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) by GC–MS, and untargeted metabolomics of urine and faeces by HILIC-HRMS. Statistical analyses used mixed-effects models adjusted for age, BMI, alcohol intake, and diet order, with Benjamini–Hochberg FDR correction for microbiome data.
**Key Results:** Faecal water genotoxicity significantly decreased from baseline after the mycoprotein phase (−8.28 ± 3.60% DNA in tail, P = 0.05) and non-significantly increased after meat (+4.91 ± 2.65%, P = 0.09), with a significant difference between phases (13.19 ± 4.41%, P = 0.01). Faecal NOC significantly decreased after mycoprotein (−1044.00 ± 377.00 nmol, P = 0.02) and increased after meat (+609.50 ± 541.00 nmol, P = 0.20), with a significant between-phase difference (1653.50 ± 677.00 nmol, P = 0.01). Urinary p-cresol sulphate significantly decreased after mycoprotein (P = 0.002) and increased after meat (P = 0.40), with a significant between-phase difference (P = 0.02). At the genus level, mycoprotein significantly increased Lactobacillus (P = 0.05), Roseburia (P < 0.001), and Akkermansia (P = 0.02), while meat increased Oscillibacter (P = 0.004) and Alistipes. The between-phase difference for Roseburia was highly significant (P < 0.001). Faecal valerate was significantly higher after mycoprotein versus meat (144.31 ± 53.76 μg/g, P = 0.02). Total BCFA decreased significantly after meat (−190.15 ± 87.24 μg/g, P = 0.01), with a significant between-phase difference (151.81 ± 86.67 μg/g, P = 0.04). Self-reported fibre intake increased significantly during the mycoprotein phase versus meat (+16.74 ± 3.65 g/day, P < 0.001).
**Clinical Implications:** This study provides the first human evidence that replacing red and processed meat with mycoprotein reduces faecal genotoxicity and genotoxin excretion while increasing beneficial gut microbes and SCFA production. The reduction in genotoxicity and NOC, coupled with increases in butyrate-producing Roseburia and mucin-degrading Akkermansia, suggests mycoprotein may lower CRC risk markers. The increases in Lactobacilli, which can bind and modify NOC, and the reduction in urinary p-cresol sulphate (a genotoxic fermentation product) further support a protective role. Limitations include the exclusively male, healthy, non-obese cohort, lack of full dietary control, and use of 16S sequencing (genus-level only). Larger, more diverse studies with longer interventions and fibre-matched controls are needed to confirm these effects and elucidate mechanisms.