The human gut contains approximately 38 trillion microbial cells, slightly more than the total number of human cells in the body. These microorganisms, collectively called the gut microbiome, perform functions no human enzyme system does: fermenting fiber into short-chain fatty acids, synthesizing vitamins, training the immune system, and producing neurotransmitter precursors including about 90% of the body’s serotonin.

The microbiome is shaped heavily by diet. What bacteria thrive in the colon depends on what they’re given to eat, and the macronutrient composition of the diet, particularly the ratio of fiber to sugar, is one of the most powerful influences on microbial community structure.

What Gut Bacteria Eat

The bacteria in the colon are largely anaerobic. They live and function without oxygen, in an environment the small intestine’s digestive enzymes never reach. They subsist primarily on material the human gut can’t digest: dietary fiber, resistant starch, and certain polyphenols.

Beneficial bacteria including Bifidobacterium and Lactobacillus species, and many Firmicutes and Bacteroidetes, ferment these substrates into short-chain fatty acids (SCFAs): primarily acetate, propionate, and butyrate. Butyrate is the primary fuel source for colonocytes (the cells lining the colon) and has documented anti-inflammatory effects on the gut and, through the circulation, systemically.

When fiber isn’t available, as in highly processed, low-fiber diets, bacteria start fermenting whatever is available, including the mucus layer lining the gut wall. Akkermansia muciniphila, a bacterium associated with metabolic health when present in moderate amounts, becomes a primary mucus consumer when fiber is scarce. Some research suggests that loss of mucus layer integrity from microbiome dysbiosis allows bacterial products (like lipopolysaccharide, or LPS) to cross the gut barrier into the bloodstream — a condition called metabolic endotoxemia.

How Sugar Affects the Microbiome

High sugar diets (particularly high-fructose and high-sucrose diets) alter microbiome composition in ways that have been extensively studied in animal models and, increasingly, in human trials.

Proteobacteria expansion. High sugar diets consistently increase the proportion of Proteobacteria, a phylum containing many gram-negative bacteria that produce LPS. Elevated LPS exposure is pro-inflammatory. This has been demonstrated in rodent models, and there’s growing human evidence suggesting that dietary patterns high in refined sugar and low in fiber promote Proteobacteria overgrowth.

Reduced diversity. Dietary variety, particularly a wide range of plant foods, correlates with microbiome diversity. Diversity is associated with metabolic health, immune resilience, and lower rates of inflammatory diseases. Western diets high in added sugar and processed food consistently show lower microbiome diversity than traditional diets or plant-rich diets in the research literature.

Bifidobacterium reduction. High sucrose diets are associated with decreased Bifidobacterium abundance. Bifidobacterium species are among the most studied beneficial bacteria, associated with fermentation of prebiotic fibers, vitamin B production, and competitive inhibition of pathogenic bacteria.

Candida overgrowth. Candida albicans, a naturally occurring yeast in the gut, can proliferate when given abundant simple sugars. The claim that sugar causes candida overgrowth is widely circulated in popular health media, often overstated. The evidence from human studies is mixed: high sugar diets increase gut Candida in some populations, but the relevance to health outcomes in people with normal immune systems is debated.

Short-Chain Fatty Acids and What Sugar Displaces

The key mechanism by which diet shapes the microbiome for better or worse is what reaches the colon. The colon’s bacteria can’t access the calories that were absorbed in the small intestine — they get what’s left over.

A diet high in added sugar and low in fiber leaves little fermentable material for beneficial bacteria. A diet high in diverse plant fiber leaves substantial prebiotic material that feeds Bifidobacterium, Lactobacillus, Faecalibacterium prausnitzii, and Roseburia, all associated with beneficial SCFA production.

Butyrate from fiber fermentation maintains the integrity of the gut lining, reduces colon cancer risk, and has anti-inflammatory effects that extend beyond the gut via systemic circulation. Its production depends on fiber availability. High sugar diets don’t actively harm bacteria that produce butyrate. They simply fail to provide what those bacteria need.

The Gut-Brain Axis

The gut and brain communicate through the enteric nervous system (the gut’s own nervous system, sometimes called the “second brain”), the vagus nerve, and the circulatory system. Gut bacteria influence this communication in ways that are an active area of research.

Lactobacillus and Bifidobacterium species produce GABA precursors. Enterococcus and Streptococcus species produce serotonin precursors. Approximately 90-95% of the body’s serotonin is produced in the gut, not the brain — by enterochromaffin cells responding partly to bacterial signals.

Whether high-sugar diets deplete gut-derived serotonin production by depleting the bacteria involved is not clearly established, but the pathway is biologically plausible and the subject of ongoing research, including clinical trials of probiotic supplementation for depression.

Human Studies

The most comprehensive human evidence comes from several directions.

The American Gut Project, a citizen-science microbiome study with data from tens of thousands of participants, found that the single strongest predictor of microbiome diversity was the number of distinct plant species consumed per week. Sugar consumption was associated with reduced diversity across the dataset.

A 2019 study in Cell by Sonnenburg and colleagues found that a diet high in fermented foods increased microbiome diversity and decreased inflammatory markers more than a high-fiber diet alone, suggesting that both substrate (fiber for bacteria to ferment) and inoculants (live bacteria in fermented food) matter for gut health.

A 2020 randomized trial in Cell Host & Microbe found that switching obese individuals from a high-sugar, low-fiber diet to a high-fiber diet shifted the microbiome toward greater Bifidobacterium and Akkermansia abundance within two weeks.

Sugar and Gut Health: Key Numbers

  • ~38 trillion microbial cells in the human gut
  • 90-95% of body’s serotonin produced in the gut
  • Microbiome diversity: strongest predictor is number of distinct plant foods per week (American Gut Project)
  • SCFA production: dependent on fermentable fiber reaching the colon
  • 3-4 days: approximate time for detectable microbiome shifts in response to major dietary change

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