Ageing as Enzyme Loss: The Role of Bacillus subtilis

Bacillus subtilis – an evolutionary enzymatic actor between the microbiome, ageing, and functional biology

Why a transient microorganism may be more systemically relevant than we have long assumed

Introduction – Ageing as a loss of functional order

Ageing is often described as an accumulation of molecular damage: DNA instability, oxidative stress, mitochondrial dysfunction. This perspective is valid, but incomplete. Increasingly, a systems-biological understanding is emerging that views ageing less as a defect and more as a gradual loss of functional order.

Enzymatic and regulatory processes are particularly affected: digestion, proteostasis, barrier function, immune balance. In parallel, the human microbiome changes. Its diversity decreases, functional redundancy is lost, and inflammatory processes increase. Notably, people with exceptionally high life expectancy often exhibit a more stable, more enzymatically active microbiome than their age peers.

In this context, an organism comes into focus that has so far been known primarily as a model organism or an industrial enzyme supplier: Bacillus subtilis.

Functional role of Bacillus subtilis in the gut

Transient germination of spores, local enzyme production, immune and microbiome modulation.

An underestimated classic of biology

Bacillus subtilis is among the best-studied microorganisms of all. Since the 1940s, it has served as a model for bacterial gene regulation, protein secretion, stress resistance, and sporulation. Its genome was fully sequenced early on, and its regulatory networks are considered paradigmatic and well understood.

However, precisely this scientific familiarity has led to B. subtilis receiving little attention in modern microbiome research. The focus is usually on obligate anaerobic gut bacteria—while transient, sporulating organisms are regarded as peripheral.

Yet B. subtilis has properties that make it highly relevant from a functional and systemic perspective.

Enzymatic breadth as an evolutionary strategy

Bacillus subtilis is not a specialist. It is a generalist with exceptional enzymatic competence. A substantial portion of its genome is directly or indirectly involved in the production and secretion of extracellular enzymes.

These include, among others:

• subtilisin-like proteases
• endo- and exopeptidases
• glycosidases
• lipases
• biofilm- and matrix-modulating enzymes
• secondary metabolites with regulatory effects

This diversity is not accidental. As a soil organism, B. subtilis lives in a nutrient-poor, competitive environment. Survival here means efficiently breaking down complex macromolecules. Enzymatic versatility is therefore not a luxury, but an evolutionary necessity.

Sporulation – functional presence without colonisation

A central feature of B. subtilis is its ability to sporulate. Spores are extremely resistant and can remain inactive for long periods. Under suitable conditions, they germinate within a short time.

In the human gut, this results in a particular biological scenario:

• spores survive gastric and bile acids
• a fraction germinates in the intestine
• metabolically active cells produce enzymes
• excretion occurs after days to weeks

There is no permanent colonisation, but there is transient functional activity. With regular intake, one can speak of functional persistence—a state of continuous biological effect without classical colonisation.

Transient functional persistence with daily spore intake
Overlap of individual germination cycles creates continuous activity.

Which enzymes are actually expressed in the gut?

The gut is not a controlled fermenter. Low oxygen availability, competitive pressure, and immune surveillance substantially limit microbial activity. Bacillus subtilis responds to this with selective expression.

Based on current knowledge, the following are expressed in the gut in particular:

• subtilisin-like proteases
• peptidases for releasing bioactive oligopeptides
• enzymes for interacting with the mucus layer
• lipopeptides such as surfactin with micro-ecological effects

These enzymes act primarily locally, but their significance is indirect and systemic—for example through:

• relieving the body’s own digestive enzymes
• reducing protein-related inflammatory stimuli
• stabilising the intestinal barrier
• modulating immunological signals

Enzymatics, the microbiome, and ageing – a functional relationship

With increasing age, several parallel developments can be observed:

• reduced endogenous enzyme production
• reduced proteostasis
• diminished autophagy
• increasing chronic inflammation
• loss of microbial diversity

Ageing can therefore be understood as a progressive loss of enzymatic and regulatory capacity. Microorganisms with high enzymatic competence do not act as substitutes, but as a functional buffer.

Enzymatic competence across the lifespan
Microbial enzymes can functionally offset age-related losses.

Microbiome ecology: more than just enzymes

Bacillus subtilis does not act exclusively through enzyme production. It also influences the microbial ecology of the gut. By producing antimicrobial lipopeptides, it can inhibit the growth of toxin-producing or pro-inflammatory microbes without destabilising the system.

This ecological effect is subtle but relevant—especially in older age, when microbiome balance becomes more fragile.

Ecological role of Bacillus subtilis in the microbiome
Containment of toxin-producing microbes while maintaining system stability.

Natto – a cultural window into functional microbiology

A traditional example of the enzymatic performance of Bacillus subtilis is natto, a fermented soy product. Under fermentative conditions, the organism produces highly active proteases.

The gut is not a natto system. Nevertheless, this example illustrates impressively what functional potential this organism carries—depending on context and environmental conditions.

Evolutionary classification: a distinct actor

From an evolutionary perspective, Bacillus subtilis is remarkable. It is neither a classical symbiont nor an opportunistic pathogen. Its strategy is different: transient system stabilisation.

Evolutionary classification of Bacillus subtilis
Between a permanent symbiont and an opportunistic pathogen.

Conclusion – an underestimated contributor to biological order

Is Bacillus subtilis a miracle remedy?
From today’s perspective, that term would be premature. Yet many key biological actors were underestimated for a long time before their systemic relevance was recognised.

Bacillus subtilis acts multifactorially:

• through enzymatic support
• through ecological regulation of the microbiome
• through containment of toxin-producing microbes
• through functional redundancy in an ageing system

Is it relevant to ageing in a functional sense?
If ageing is understood as a loss of functional capacity, then any intervention that supports enzymatic activity, microbial balance, and inflammation control over the long term can reasonably be considered functionally stabilising in the context of age-related processes .

Perhaps its greatest strength lies precisely in the fact that it:

• is not a permanent coloniser
• does not create dependency
• does not maximise a single function
• but stabilises biological order

What may still appear as a marginal topic today could prove to be a foundational building block of a functional understanding of health and longevity.

Literature & further sources

(Selection – for deeper reading)

Sonenshein, A. L., Hoch, J. A., & Losick, R. (Eds.).
Bacillus subtilis and Its Closest Relatives: From Genes to Cells. ASM Press, 2002.
https://onlinelibrary.wiley.com/doi/book/10.1128/9781555817992

Harwood, C. R. (1992).
Bacillus subtilis and its relatives: molecular biological and industrial workhorses.
Trends in Biotechnology, 10(7), 247–256.
https://doi.org/10.1016/0167-7799(92)90233-

López-Otín, C. et al. (2013).
The hallmarks of aging. Cell, 153(6), 1194–1217.
https://doi.org/10.1016/j.cell.2013.05.039 

Nicholson, J. K. et al. (2012).
Host–gut microbiota metabolic interactions. Science, 336(6086), 1262–1267.
https://www.science.org/doi/10.1126/science.1223813

Rampelli, S. et al. (2013).
Functional metagenomics of the human gut microbiome in the elderly. PNAS, 110(10), 4046–4051.
https://doi.org/10.1073/pnas.1219993110

Author: Andreas Kraus
Owner & Managing Director · Scientific Lead

Editorial & Research: Selina Kraus
Journalist (B.A.) · Master’s studies in Management & Leadership of Online Marketing

All illustrations: Original work (conceptual illustrations). 

Editorial note:
This article serves the scientific classification of microbiological and systems-biological concepts. It does not constitute a health-related statement, a recommendation, or a substitute for medical advice. It is intended as a scientific perspective article. It develops a systems-biology hypothesis on the role of transient microorganisms in the context of age-related functional changes and makes no claim to clinical evidence or therapeutic derivation.