How a High-Fat Diet Disrupts Everything
The hidden kingdom living inside you is at war, and your diet is shaping the battlefield.
When we think about gut health, bacteria typically steal the spotlight. But emerging research reveals a forgotten kingdom within us—the gut mycobiome, our resident fungal community—that plays a crucial role in health and disease.
What we eat, particularly high-fat diets, doesn't just alter our bacterial gut residents; it completely restructures the complex relationships between bacteria and fungi in ways that may contribute to obesity and metabolic disorders. This article explores the fascinating discovery of how high-fat diets disrupt these interkingdom relationships in the gut.
For years, the conversation around gut microbiota has been dominated by bacteria. Yet our digestive tract hosts a diverse ecosystem of microorganisms including archaea, viruses, and fungi. Though fungi represent a much smaller proportion of our gut microbes—comprising only about 0.1% of the total microbial metagenome—they play significantly outsized roles in our physiology 3 .
10¹¹–10¹² cells per gram in the colon
10² to 10⁶ CFU/g in the colon
Fungal imbalances linked to obesity and GI conditions
Recent research has revealed that gut fungi are not merely passive residents but active participants in maintaining health—and when disrupted, contributors to disease. Fungal imbalances have been implicated in gastrointestinal conditions, metabolic diseases, and even the development of obesity 3 .
A groundbreaking 2017 study published in mSphere sought to understand how high-fat diets affect both bacterial and fungal communities in the gut, and crucially, how they alter the relationships between these different types of microorganisms 1 5 .
Mice were divided into two groups—one fed a high-fat diet (60% calories from fat) and another fed standard chow (18% calories from fat) 7 .
Using advanced genetic sequencing techniques, the researchers analyzed the gut communities by examining the 16S rRNA genes for bacteria and the internal transcribed spacer region 2 (ITS2) of fungal ribosomal DNA for fungi 1 5 .
The team didn't stop at cataloging which microbes were present; they also constructed co-abundance networks to understand the complex relationships between different bacterial and fungal species 1 .
This comprehensive approach allowed scientists to see not only which microbes were affected by the high-fat diet but how the entire social network of the gut community was being restructured.
The high-fat diet caused substantial changes in both bacterial and fungal communities. Researchers found 19 bacterial taxa and 6 fungal taxa whose abundances significantly changed between the two diet groups 1 7 .
The bacterial findings aligned with previous obesity research—Firmicutes increased while Bacteroidetes decreased, a pattern associated with enhanced energy harvest from food 7 . But the fungal changes revealed something new: a high-fat diet doesn't just change which fungi are present; it overhauls the entire fungal landscape.
Perhaps the most striking discovery was how the high-fat diet affected relationships between bacteria and fungi. The researchers observed what they called "strong and complex diet-specific coabundance relationships" between bacterial and fungal species in mice fed standard chow 1 5 .
Complex, interconnected network
Simplified, disconnected network
Visual representation of microbial network complexity under different diets
In simpler terms, different microbial species tended to rise and fall together in predictable patterns—some were "friends" (positive correlations) while others were "competitors" (negative correlations). These relationships formed an intricate ecological network.
When mice were fed a high-fat diet, this social network dramatically simplified. The number of coabundance correlations was drastically reduced, indicating that the high-fat diet wasn't just changing which microbes were present, but how they interacted with each other 1 . The rich, complex web of relationships became far simpler and less connected.
The disruptions extended beyond which microbes were present and how they related to each other. The researchers also examined the predicted functional capabilities of the gut communities.
They found that 46 functional modules related to metabolism were significantly different between the two groups. Specifically, pathways involved in carbohydrate and lipid metabolism, energy metabolism, and nucleotide and amino acid metabolism were decreased in mice fed the high-fat diet 7 .
| Metabolic Pathway Category | Effect of High-Fat Diet |
|---|---|
| Carbohydrate metabolism | Decreased |
| Lipid metabolism | Decreased |
| Energy metabolism | Decreased |
| Nucleotide metabolism | Decreased |
| Amino acid metabolism | Decreased |
This suggests that high-fat diets don't just change who's living in the gut; they change what the community is capable of doing, potentially reducing its metabolic versatility.
Understanding these microbial communities requires sophisticated tools. Here are the key reagents and methods used in this type of research:
| Research Tool | Function | Specific Example |
|---|---|---|
| ITS2 Sequencing | Identifies fungal species | Internal Transcribed Spacer 2 (ITS2) region of fungal rDNA 1 |
| 16S rRNA Sequencing | Identifies bacterial species | 16S ribosomal RNA genes of bacteria 1 |
| Co-abundance Network Analysis | Maps relationships between microbes | Correlation patterns between bacterial and fungal abundances 1 |
| Functional Prediction | Predicts metabolic capabilities | Kyoto Encyclopedia of Genes and Genomes (KEGG) modules 7 |
This research reveals that the story of diet, gut health, and obesity is far more complex than we understood. It's not just about bacteria or fungi alone—it's about the entire ecological community and the intricate relationships between its members.
The disruption of these interkingdom relationships by high-fat diets may represent a previously overlooked mechanism through which poor nutrition contributes to obesity and metabolic disorders. As one commentary noted, "Changes in relationships between bacteria and fungi triggered by a high-fat diet might be involved in the development of obesity" 7 .
Future research will need to untangle the cause-and-effect relationships—whether these microbial changes drive metabolic disease or are consequences of it. Either way, the message is clear: when we consider gut health, we must look beyond bacteria and appreciate the full community of microorganisms that call our bodies home.
The hidden fungal kingdom in our gut, though small in numbers, appears to play a significant role in our metabolic health—and it's profoundly affected by what we eat. As science continues to unravel these complex relationships, we move closer to understanding how to nourish all the residents of our inner world for better health.
This article is based on the study "High-Fat Diet Changes Fungal Microbiomes and Interkingdom Relationships in the Murine Gut" published in mSphere (2017) and subsequent research in this emerging field.