Microbiome Science: What We Know vs. What We Assume

During my undergraduate studies, discussions often focused on the gut microbiota’s role in gastrointestinal function, immune support, and its links to neurological disease.

At that time, I uncritically accepted statements such as: 

“The microbiota is so essential that we must avoid ingredients that harm it, such as sweeteners, simple sugars, and saturated fats.” 

However, to avoid oversimplifying food into “good” versus “bad,” I believe it is illogical to shun an ingredient solely because it alters the microbiota in vitro or in humans—what matters is whether these changes lead to meaningful clinical outcomes.

A Microbiome Primer

The term microbiota defines the microorganisms, primarily bacteria, viruses, and fungi, inhabiting various niches or ecosystems in the body. The microbiome encompasses all microorganisms, their genetic information, and their activities within those niches or ecosystems. The intestinal microbiota is the diverse community of microorganisms residing in the human gut. This community is predominantly composed of two phyla:

1. Bacteroidota – gram-negative bacteria with relatively thin cell walls
2. Firmicutes – gram-positive bacteria with thicker cell walls 

Together, these two groups constitute about 90% of the bacteria in the human gut. At the same time, other phyla, such as Proteobacteria and Actinobacteria, play key roles in maintaining intestinal homeostasis and overall health.

The intestine supplies a suitable environment and essential nutrients, and in return, the microbiota provides substrates, vitamins, and energy to its human host. Fiber fermentation produces short-chain fatty acids (SCFA)—metabolites that promote the growth and differentiation of epithelial cells and contribute to vitamin synthesis, among other benefits.

The intestinal microbiota communicates with our peripheral organs via the metabolites, the chemical messengers it produces. While significant changes in the microbiome’s overall composition might trigger negative responses and potentially accelerate diseases, current research does not clearly demonstrate whether these effects cause or are the result of these conditions; they only demonstrate an association. Other factors, including diet and medications (especially antibiotics), shape the microbiota and the microbiome. 

Formation of the Microbiota

Initially, scientists believed that the fetus remained sterile in the womb and that colonization occurred during birth. However, recent evidence suggests that bacteria from the mother’s oral, vaginal, urinary, and intestinal microbiota can reach the placenta and fetus.

The type of delivery also plays a crucial role. Babies born by cesarean section display a greater abundance of Firmicutes, whereas those born vaginally exhibit higher concentrations of Bifidobacterium and Bacteroides. These differences are notable during the first three months but tend to disappear after six months.

The microbiota continues to develop through exposure to the mother’s skin and breastfeeding, with breast milk contributing 25-30% of the baby's bacteria and providing oligosaccharides, a carbohydrate acting as a prebiotic to support beneficial microorganisms.

Among other influences:

• Geographic differences, e.g.,  the Japanese hosts phyla such as Bacteroidota, Firmicutes, and Actinobacteria, while the Yao ethnic group in China exhibits a higher abundance of the Megamonas genus, a type of bacteria typically found in the intestines of carnivores.
• The genus Bifidobacterium predominates during childhood, while Firmicutes and Bacteroidota become the dominant phylum over time. In older adults, there is a relative increase in Bacteroidota, accompanied by a rise in Enterobacteriaceae and Streptococci.
• Medications, especially antibiotics, can destabilize the microbiota and compromise immune regulation.
• Stress alters intestinal motility and permeability, both of which alter the release of those metabolites or chemical signals activating the hypothalamic-pituitary-adrenal axis, which regulates metabolism and immunity.
• Physical exercise impacts the microbiota, with moderate exercise promoting beneficial microorganisms, while intense exercise can disrupt short-chain fatty acid (SCFA) metabolism.

Of course, what we feed the microbiota, our daily diet directly shapes the structure and activity of the microbiota. The dominant intestinal flora correlates with the proportions of macronutrients—carbohydrates, fats, and proteins—in what we eat. 

Specific dietary patterns influence the microbiota. For those following an Adkins-like diet, restricting carbohydrates, bacterial diversity, and SCFA production decrease. Vegetarians tend to have a notable presence of Prevotella copri, while non-vegetarians often show a predominance of Bacteroides vulgatus. The wide variations in our global eating habits make it unlikely that one universally ideal diet exists for gut health. Given this scenario, do these changes in the microbiota and microbiome truly lead to clinically significant health outcomes?

Dietary Interventions:

A newly published study in Nutrients compares two juice-based diets with a plant-based, whole-food diet over three weeks to assess their oral and intestinal microbiome effects. Fourteen participants, with an average age of 22.7 and BMIs between 18.5 and 30, were included in the analysis, which involved collecting microbial samples of their oral and gut microbiomes. 

After a three-day “elimination diet” consisting of fresh organic fruits, vegetables, eggs, and eight glasses of water, excluding alcohol, caffeine, sugar, processed foods, dairy, red meat, and gluten, participants were randomly assigned to one of three dietary interventions:

• Juice Fasting Diet (800–900 kcal/day): Exclusive consumption of cold-pressed juices.
• Regular Ad Libitum Diet + Cold-Pressed Juice
• Plant-based, whole-food diet (800–900 kcal/day)

Analyses of the collected samples demonstrated the following:

Gut Microbiome: 

The diets did not produce significant differences in the gut’s overall diversity or composition. The plant-based and juice-only diet participants exhibited greater interindividual variation in gut microbiome composition compared to those on the juice-with-food diet. Although there were no statistically significant changes in overall intestinal bacterial families, trends emerged.

Before discussing the implications of these bacterial increases and reductions, remember these are correlations, challenging our ability to definitively establish causation regarding health changes.

For example, the elimination diet may harm the oral microbiome because it increases Proteobacteria, an inflammatory microorganism. However, the same diet also raised the levels of two bacteria typically found in the oral cavities of healthy individuals not associated with oral diseases. Additionally, it reduced the concentration of Lachospiraceae sp., a bacterium linked to cognitive impairment, suggesting a potential beneficial change in health within this mechanistic framework.

In the gut microbiome, the elimination diet increased the abundance of Bacteroides uniformis, a fiber-degrading bacterium known to help restore immune balance in obese animal models. It inhibited the growth of Bacteroides fragilis and Bacteroides caccae, both associated with inflammatory intestinal diseases and colorectal cancer. These bacterial changes help control intestinal inflammation, maintain immune balance, and enhance resistance to pathogens.

In contrast, the dietary interventions generally had minor effects on both the intestinal and oral microbiota but were associated with adverse health outcomes. Many taxa that increased with the juice and juice-plus-food diets have been linked to:

• Elevated inflammatory markers
• Cardiovascular disease
• Periodontal disease

Based on these observations, the study concludes that particularly the juice-only diet, which increased pro-inflammatory bacterial families and taxa associated with intestinal permeability and cognitive decline—can significantly impact various aspects of health. 

We might mistakenly believe that achieving a healthy microbiome simply requires avoiding a juice-only diet, which is, in my opinion, a good idea for other reasons, and adopting an elimination diet, given its association with health benefits. However, several important factors significantly challenge the authors' optimistic conclusion.

First, despite concerns about the effects of the intervention diets, the observed changes in both microbiomes were relatively minor. The 14-day post-intervention period also showed a trend toward reestablishing pre-intervention microbiome compositions, suggesting that three days of dietary intervention were insufficient for meaningful long-term modulation. The study's small sample size and short intervention period limit the certainty of its findings. The study's limitations and the fact that most associations between gut microbiota and health outcomes are derived from animal models prevent us from confidently stating that dietary interventions definitively cause health problems or provide treatments.

Based on these considerations, a more objective analysis of the study suggests that the only concrete finding is that specific dietary patterns temporarily alter bacterial phyla in the oral and gut microbiota while those diets are followed.

Although the gut microbiota plays an undeniably important role, we still cannot determine whether its microorganisms and the changes caused by external factors drive the observed health benefits or merely reflect healthy lifestyle habits. The research suggests that the microbiota adopts a "healthier" pattern when we follow core health principles: regular exercise, effective stress management, a balanced diet, and moderate alcohol consumption. The basics always work.

[1] A group consisting of one or more organisms that share common characteristics.

Source: “Gut bacteria formation and influencing factors” Microbiology Ecology DOI: 10.1093/femsec/fiab043

Effects of Vegetable and Fruit Juicing on Gut and Oral Microbiome Composition Nutrients DOI: 10.3390/nu17030458