Lactobacillus reuteri and Its Interaction with Genes: The Gut Microbe That Talks to Your DNA

Lactobacillus reuteri (L. reuteri) is a powerful probiotic species naturally found in the gastrointestinal tracts of humans and animals. As part of the lactic acid bacteria group, it’s known for producing beneficial compounds and maintaining gut health. But beyond digestion, emerging research reveals that L. reuteri can interact with our genes—modulating immune function, inflammation, neurotransmitter production, and even behavior.

 

Let’s dive into how L. reuteri communicates with our genome and what that means for our health.

 

🦠 What Is L. reuteri?

1. reuteri is a commensal bacterium—meaning it normally lives in harmony with us. It was once common in the human gut, but its prevalence has decreased in modern societies due to antibiotic use, C-section births, and reduced exposure to natural microbes.
   
   
2. reuteri is special because it produces:

• Reuterin: A broad-spectrum antimicrobial that fights harmful pathogens
  
• Short-chain fatty acids (SCFAs): Like acetate and lactate, which nourish gut cells
  
• Bioactive peptides: That affect inflammation and immune responses
  
  

🧬 L. reuteri’s Genetic Influence: Epigenetics & Host Gene Expression

1. reuteri interacts with our epigenome, which is the layer of chemical modifications (like DNA methylation) that controls how genes are turned “on” or “off” without changing the underlying DNA sequence.
   

1. Modulation of Inflammatory Genes

1. reuteri has been shown to downregulate pro-inflammatory genes, including:

• NF-κB pathway: A key driver of inflammation. L. reuteri reduces NF-κB activity, leading to lower expression of IL-6, TNF-α, and other inflammatory cytokines.
  
• IL-10 stimulation: It boosts IL-10, an anti-inflammatory cytokine, via epigenetic modifications.
  
  

These effects are partly mediated by SCFAs, which act as histone deacetylase (HDAC) inhibitors—molecules that open up the DNA structure and allow anti-inflammatory genes to be expressed.

 

🧠 Gut-Brain Connection and Neurotransmitter Genes

1. reuteri impacts neurotransmitter systems in the gut-brain axis:
   
   

1. Oxytocin and Social Behavior

In mouse models, L. reuteri increases oxytocin production by stimulating the vagus nerve. This hormone plays a crucial role in social bonding, stress regulation, and even autism-related behaviors.

Mechanistically, this involves upregulation of genes like:

• OXTR (oxytocin receptor gene)
• Modulation of BDNF (brain-derived neurotrophic factor), which supports neuroplasticity
  
  

2. Serotonin and Dopamine Pathways

1. reuteri may also influence:

• TPH1: The gene that converts tryptophan into serotonin in the gut
  
• COMT and MAOA: Enzymes that break down neurotransmitters—possibly affected by microbiota-produced cofactors
  
  

🧬 L. reuteri and Methylation Pathways

The gut microbiome plays a role in the one-carbon metabolism pathway, which regulates DNA methylation, a key epigenetic mechanism. L. reuteri may influence:

• Folate availability: Some strains produce folate, supporting the methylation cycle
  
• SAM (S-adenosylmethionine) levels: As a methyl donor, SAM affects gene silencing or activation
  
  

This can be especially relevant in individuals with MTHFR, MTRR, BHMT, or COMT gene variants, who may have altered methylation capacity. By improving gut health and providing cofactor support, L. reuteri might help buffer the impact of these polymorphisms.

 

🧬 Immune System Programming in Early Life

1. reuteri can influence T-regulatory cell (Treg) development in infants, which depends on:

• FOXP3 gene expression: A master regulator of immune tolerance
  
• Histone acetylation in immune cells: Which determines whether genes like IL-10 or TGF-β are activated
  
  

Early colonization with L. reuteri has been linked to reduced risk of:

• Allergies
  
• Autoimmune diseases
  
• Chronic inflammation
  
  

🧬 Host Genetic Variants That Influence Response to L. reuteri

Host genetics also determines how well someone responds to L. reuteri. For instance:

• TLR2 and TLR9 polymorphisms (toll-like receptors) affect how the immune system senses L. reuteri’s cell wall components
  
• VDR gene variants (vitamin D receptor): Vitamin D enhances gut barrier integrity, and VDR also modulates microbial responses
  
• CD14 gene polymorphisms: Related to recognition of bacterial lipopolysaccharides (LPS), which can impact inflammation control
  
  

Thus, probiotic efficacy can be personalized based on your genetic makeup.

🌿 Clinical Applications and Research Highlights