Balancing substrate accessibility and inhibition in anaerobic digestion: Trade-offs, microbial responses, and process implications

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Anaerobic digestion is a central technology for converting organic wastes into renewable energy and valuable by-products, yet its performance is constrained by the coupling between substrate accessibility (i.e., the availability of organic matter for enzymatic and microbial degradation) and inhibitor formation. This review provides an integrated analysis of this relationship, showing how pretreatment enhances biodegradability while simultaneously promoting inhibitory compounds that impair microbial activity. Hydrolysis is identified as the main rate-limiting step, strongly influenced by lignocellulosic recalcitrance. Although pretreatment improves hydrolysis kinetics and methane yields, it can lead to the accumulation of phenolics, ammonia, furans, and volatile fatty acids, which disrupt microbial metabolism. Advances in ADM1-based modeling enable the integration of kinetic and toxicity effects, improving predictive capabilities. Mitigation strategies, including co-digestion, adsorption, and microbial consortium engineering, enhance process stability. Overall, anaerobic digestion performance is governed by an operational window balancing accessibility and inhibition, supporting the optimization of scalable bioprocesses.