Gut Microbiome and Chronic Inflammation Without Diagnosis

When Inflammation Persists but Tests Say “Everything Is Normal”

Do you feel tired for no reason, experience aches that move around your body, or perhaps suffer from mild gastrointestinal discomfort, yet all your lab tests come back “normal”? If so, you’re not alone. Thousands of people deal daily with symptoms linked to subclinical or low-grade inflammation, without a precise diagnosis. In such cases, the answer may lie in the gut microbiome. The human body hosts trillions of microorganisms, mainly in the gut. The totality of these microbes, known as the microbiome, plays an active role in regulating the immune system, gut function, and the maintenance of homeostasis. However, when this balance is disrupted, a condition called dysbiosis can occur. Dysbiosis, meaning the qualitative and quantitative alteration of the normal flora, may not directly cause illness, but it can create an environment of low-grade inflammation that gradually undermines health. This inflammation, often undetectable by standard medical tests, is associated with various chronic conditions—from metabolic syndrome and insulin resistance, to skin issues, fatigue, and psychological symptoms. What’s important is that, through functional medicine and advanced diagnostic tools, we can now detect these inflammatory processes at an early stage and address them individually—by analyzing their root causes rather than simply suppressing the symptoms.

The Biology Behind “Silent” Inflammation

The link between the gut microbiome and chronic inflammation without a precise diagnosis is now scientifically well established. Under normal conditions, the gut acts as a barrier and regulator. The epithelial cells of the intestine, working together with microbes and the immune system, form a complex but harmonious ecosystem that protects the body from pathogens and regulates immune response.
However, when this balance is disrupted (dysbiosis), things change:

• Leaky Gut: Allows substances such as lipopolysaccharides (LPS), microbial fragments, and metabolites to pass into the bloodstream. The immune system recognizes these substances as "invaders," triggering low-grade activation.
• Activation of inflammatory pathways: The continuous presence of these substances stimulates TLR receptors (Toll-like receptors), activating pathways like NF-κB, which lead to the production of cytokines such as IL-6, IL-1β, and TNF-α.
• Endotoxemia: A low-grade but chronic circulation of endotoxins, mainly LPS, creates a state of metabolic inflammation (metaflammation), which is not easily detected by standard blood tests.

The result is a body that is “burning internally” without appearing sick. The immune system remains on constant alert, depleting energy reserves, disrupting hormonal mechanisms, and burdening metabolic organs like the liver and pancreas. Studies highlight that even in individuals without apparent disease, dysbiosis is associated with measurable increases in inflammatory activity, renal stress, and impaired glycemic control. Diagnosing these subclinical conditions requires specialized, functional tests that are not part of a typical medical check-up. At this point, functional medicine offers the appropriate tools.

Functional Medicine: Seeking the Causes, Not Just the Symptoms

Functional Medicine does not focus solely on recognizing and suppressing symptoms. On the contrary, it targets the root causes of health issues by examining the organism holistically—its metabolic balances, interactions with the environment, and, of course, the composition and function of the microbiome. This approach is ideal for addressing chronic inflammation without a precise diagnosis.

Step One: Case History and Symptom Analysis
Each case begins with a comprehensive history, not just medical, but also nutritional, bowel-related, emotional, and toxic exposure. Questions such as:

• How often do you experience bloating, constipation, or diarrhea?
• Is there a sense of “mental fog”?
• Which foods cause intolerance?
• Is there frequent fatigue after meals?

Provide valuable clues about disturbances in microbial balance and metabolic function.

Step Two: Targeted Microbiome and Inflammation Testing
Traditional blood tests may still appear normal. Functional Medicine employs specialized diagnostic methods that reveal low-grade inflammation, dysbiosis, and metabolic imbalances.
Some of the most critical tests include:
EnteroScan®: Analysis of the gut microbiome, metabolites, endotoxins, and inflammatory markers through stool samples. It provides a detailed overview of the balance between beneficial and pathogenic bacteria, as well as the production of butyric acid, a short-chain fatty acid with anti-inflammatory effects.
NutriScan®: It identifies deficiencies in vitamins, micronutrients, and metabolic pathways. Such imbalances can compromise immune homeostasis.
Chronic Inflammation Profile: CRP (C-reactive protein), IL-1, IL-6, IL-8, TNF-α, LPS.While these are classic markers, in chronic inflammation, they usually appear at borderline levels. These values, combined with EnteroScan findings, carry exceptional diagnostic value. Serum LPS (lipopolysaccharide) measurement detects potential endotoxemia.
DetoxScan®: Assesses the body's antioxidant status in relation to oxidative stress, a key factor in chronic inflammatory states.

Step Three: Reversing the Condition
Once the mechanisms causing inflammation are identified (dysbiosis, leaky gut, oxidative stress, metabolic disruption), the physician proceeds with a targeted intervention using:

• Probiotics and prebiotics of specific strains
• Dietary modifications based on test results
• Anti-inflammatory nutrients
• Detoxification support (mainly through the liver and gut)

This method of care enables us to support patients with chronic symptoms who may have been dismissed or misunderstood by the conventional medical model.

Restoring the Microbiome Begins with Your Plate and Daily Habits

The health of the microbiome—and by extension, the prevention or management of low-grade inflammation—does not rely solely on pharmaceutical interventions or supplements. On the contrary, it is based on simple, consistent lifestyle and dietary changes. The metabolites of gut bacteria interact directly with the immune, endocrine, and cardiovascular systems, exerting positive or negative effects depending on the host’s nutritional background.
Guidelines for Restoring Microbial Balance:
A diet rich in dietary fiber (prebiotics). Dietary fiber is the primary “fuel” for beneficial gut bacteria. When fermented in the colon, they produce short-chain fatty acids (such as butyric acid), which have anti-inflammatory and healing effects on the intestinal lining.

• Foods that contribute:
• Legumes, root vegetables, oats
• Green vegetables, bananas, garlic, and leeks
• Resistant starch (e.g., cooled rice or potatoes)

Consumption of probiotic foods. Although probiotic supplements play an important role when targeted, daily intake of probiotic-rich foods supports the natural diversity of the microbiome.
Options include:

• Fermented vegetables (cabbage, carrot, beetroot)
• Kefir, yogurt with live cultures
• Miso, tempeh, kombucha (in controlled amounts)

Reduction of sugar intake and processed foods. Processed sugars and industrial oils disrupt microbiome balance, promote pathogenic bacteria, and increase intestinal permeability. Alternatives: Use natural sweeteners like stevia or honey in small amounts.
Intermittent fasting and caloric regulation. Intermittent fasting (e.g., 16:8) has been shown to enhance microbial diversity and reduce post-meal inflammation. It also allows gut barrier restoration during fasting windows.
Physical activity and contact with nature. Moderate exercise (walking, yoga, cycling) 3–5 times per week promotes the release of anti-inflammatory cytokines. Nature exposure and soil contact have been linked to greater microbial diversity.
Limiting medications that affect the microbiome. Antibiotics, antacids, oral contraceptives, and NSAIDs alter the composition of the microbiome and increase gut permeability. Their use should be targeted and necessary.
Quality sleep and stress management. Poor sleep and chronic activation of the HPA axis (hypothalamus–pituitary–adrenal) disrupt the microbiome through increased cortisol and inflammatory activity. Techniques like meditation, guided breathing, and a regular sleep routine support balance.

The Inflammation You Can’t See, But That’s There

Chronic inflammation without a precise diagnosis is one of the most overlooked issues in modern medical reality. Patients experience daily discomfort, fatigue, mood disturbances, indigestion, and other non-specific symptoms, without receiving answers from standard medical protocols. As we have seen, the gut microbiome lies at the core of this condition. Dysbiosis, leaky gut, and immune dysregulation are the key axes of a silent inflammation that may not always be measurable by conventional blood tests, but significantly impacts health. Functional Medicine gives us the tools to detect this state accurately, to identify the mechanisms that sustain it, and to proceed with personalized interventions—aimed not just at relief, but at the restoration of function. Change is not instantaneous, nor simple. It requires conscious participation, consistency, and support from a scientifically trained health professional. But the results — more energy, better sleep, improved mood, a healthier gut — are worth every step of the process.

References:

1. Palazzi, C. M., Ciampaglia, G., Binato, B., Ragazzini, M., & Brunetta, E. (2025). Position Statement of the Microbiota International Clinical Society (MICS). Frontiers in Microbiomes.
2. Shi, Y. P., Pan, Z. L., Zhang, J., Xue, L. Y., et al. (2025). Gut dysbiosis, low-grade inflammation, and renal impairment severity in elderly diabetic nephropathy. World Journal of Nephrology.
3. Cui, X., Li, J., Yang, T. (2025). Gut Microbiota-Derived Metabolites and Cardiovascular Diseases. Frontiers in Cellular and Infection Microbiology.