Our Tests Intestinal Dysbiosis
Firmicutes/ Bacteroidetes Ratio
A healthy gut microbiota is vital to our wellbeing—it helps to establish and maintain our immune system, fend off opportunistic pathogens, extract nutrients and energy from foods we cannot digest (e.g., dietary fiber), produce vitamins, and stimulate communication between the gut and brain.1-5 The beneficial end-products of fiber fermentation are short-chain fatty acids (SCFAs), which nourish the gut lining and regulate food intake, inflammatory tone, and insulin signaling.1,6 Microbiota diversity is dependent on both diet and colonic transit time, and may confer resilience to stress.2,7 Overall microbial composition affects the structural integrity of the gut lining and, although influenced by our genetic background and maternal flora, also reflects what we eat.5,8
Dysbiosis is an undesirable shift in the microbiota composition—an imbalance between protective and potentially harmful microbes—that can damage the gut lining and lead to chronic diseases.2,9 In addition to pathogens and toxins, a high-fat, high-sugar, low-fiber (standard Western) diet may induce dysbiosis and reduce microbial diversity.2,10 Over time, dysbiosis can cause impaired glucose and lipid metabolism, aberrant immune responses, intestinal permeability, and metabolic endotoxemia,3,9 paving the way for cardiometabolic, autoimmune, and other inflammatory disorders.1-3 Gastrointestinal imbalance is compounded by other, all-too-common factors: a sedentary lifestyle, high stress levels, excessive alcohol intake, and gut-damaging medications.4,11-13 Chronic dysbiosis can alter gut pH and disrupt the epithelial mucus layer, creating space for pathogens to flourish.2,14
In humans, ~90% of the gut bacteria are represented by two phyla—Firmicutes (60–80%) and Bacteroidetes (15–30%).15,16 The Firmicutes phylum encompasses more than 250 genera, including Lactobacillus and Clostridium, while Bacteroidetes includes around 20 genera, the most abundant being Bacteroides. Both phyla produce beneficial SCFA from indigestible carbohydrates that reach the colon, with Firmicutes being the main butyrate-producers and Bacteroidetes producing mainly acetate and propionate.16 The ratio of Firmicutes to Bacteroidetes in the stool is a gauge of overall gut microbiota balance.
Clinical Utility & Indications
Untreated intestinal dysbiosis may underpin a variety of chronic diseases1,2,9:
- Inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and colon cancer
- Gastric ulcers, nonalcoholic fatty liver disease, and cardiometabolic diseases
- Allergic disorders and autoimmune disorders (e.g., celiac disease, rheumatoid arthritis, eczema)
- Mood disorders (e.g., anxiety, depression)
A shift in the Firmicutes to Bacteroidetes ratio (F/B ratio) may be influenced by various factors and conditions:
- Changes in nutrition, digestive secretions, use of prescription medications, and alterations in gut transit time all contribute to a decrease in the F/B ratio and microbial diversity with age.16,17
- Higher F/B Ratios have been associated with a standard Western diet.17 Evidence suggests that Bacteroidetes communities can shift according to dietary modulation and weight change, whereas Firmicutes numbers are more dependent on one’s genetic makeup.15,17
- Antibiotic-associated diarrhea, Crohn’s disease, and ulcerative colitis have been correlated with decreases in Firmicutes strains, a concomitant increase in Bacteroidetes (low F/B ratio), and a reduced gut biodiversity.9,18
- Although obesity and energy intake can affect the microbiota, studies fail to demonstrate a consistent relationship with the F/B ratio.19 However, metabolic comorbidities have been associated with a higher ratio in obese patients.20
- Dysbiosis has been suggested to play a role in the development of type 2 diabetes (T2D).1-3 Patients with T2D have a lower F/B ratio than nondiabetic controls with worsening glucose tolerance as the F/B ratio decreases.21
F/B Ratio Cut Points and Interpretation
|F/B ratio||≤ 0.5||0.6 – 0.9||1.0 – 5.6||5.7 – 9.1||≥ 9.2|
|Firmicutes log10 CFU/g||≤ 8.6||8.7 – 11.7||≥ 11.8|
|Bacteroidetes log10 CFU/g||≤ 8.1||8.2 – 11.6||≥ 11.7|
Firmicutes and Bacteroidetes are reported as log10 CFU/g. This means that the Firmicutes/Bacteroidetes Ratio can be high or low when the individual values of both bacterial phyla are within the optimal range.
– For example, if the Firmicutes result is 10 and the Bacteroidetes result is 9 (a 1-unit difference) the Firmicutes/Bacteroidetes ratio will be 10 (mildly elevated), but if the Firmicutes result is 11 and the Bacteroidetes result is 9 (a 2-unit difference) the Firmicutes/Bacteroidetes ratio will be 100 (high).
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20. Louis S, et al. PLoS One 2016;11(2):e0149564.
21. Larson N et al. PLoS One 2010;5(2):e9085.
Short Chain Fatty Acids
Humans lack the enzymes needed to break down the bulk of dietary fiber and other indigestible complex carbohydrates (e.g., cellulose, resistant starch, and oligosaccharides). Such food components are instead fermented by bacteria in the colon to produce short chain fatty acids (SCFA), primarily n-butyrate, acetate, and propionate. These beneficial SCFA have immunomodulatory and anti-inflammatory properties, provide energy to nourish the colonic epithelial cells and intestinal microbiota, and exert numerous positive effects on gut homeostasis:1-7
- Protecting the gut from pathogens by lowering luminal pH and upregulating expression of antimicrobial peptides8,9
- Maintaining the intestinal barrier by fostering mucosal proliferation, mucin production, and tight-junction integrity5,7
- Promoting sodium-dependent water absorption in the colon as a means to preserve fluid and electrolytes10
- Signaling increased dietary intake via the sympathetic nervous system to reduce excessive energy in the body by increasing heart rate and thermogenesis11
- Activating G-protein coupled receptors on enteroendocrine cells to regulate secretion of hormones involved in gut motility and energy metabolism (e.g., leptin, peptide YY, glucagon-like peptide-1, and ghrelin)12
- Indirectly regulating appetite and food intake (by increasing satiety), insulin sensitivity, and fat accumulation13,14
Although chemically similar, SCFA are metabolized differently and exert unique physiological effects.5,14 n-Butyrate has received most attention as the major fuel for colonic enterocytes, helping in barrier reinforcement and repair.3,7,15 Its anti-inflammatory functions include regulating neutrophil migration and inhibiting cytokine release from immune cells.4,15 Acetate (the most abundant SCFA) and propionate have weaker trophic and protective effects on the gut epithelium, and are carried via the blood to the liver and peripheral tissues for use in lipid (acetate) or glucose (propionate) synthesis.1,3,6,7,14
The type and amount of SCFA produced in healthy individuals largely depends on microbiota composition, quantity of carbohydrate consumed, absorption capability, and colonic transit time.1,2,3,6 90–95% of the SCFA are normally absorbed in the colon; the rest are excreted with the stool. Fecal SCFA levels reflect dietary fiber intake and are considered a useful biomarker of gut microbiota activity and health.3,16
Clinical Utility & Indications
Given their health-promoting effects, low fecal SCFA levels are considered detrimental and may reflect intestinal dysbiosis (with a lack of beneficial bacteria) and/or inadequate fiber intake, with multiple clinical implications:
- Low levels of bacteria that produce n-butyrate and propionate have been linked to inflammatory diseases such as ulcerative colitis (n-butyrate) and childhood asthma (propionate).17,18
- Patients with advanced colorectal adenoma have reduced fecal n-butyrate and studies indicate that SCFA may play an important role in protection against colorectal cancer.19-21 These SCFA, especially n-butyrate, can act in secondary chemoprevention by slowing growth and triggering apoptosis of colon cancer cells, and in primary prevention by activating drug metabolizing enzymes, reducing the mutation burden of carcinogens.20,21
- Consistent with their role in glucose homeostasis, fecal SCFA are often low when metabolic disease is present.12 Type 2 diabetes and gout have been associated with reduced abundance of butyrate-producing bacteria.13,22,23
- Low SCFA levels are associated with gut motility problems. Transit times > 50 hours may lead to reduced fecal SCFA due to enhanced colonic uptake.3
- Antibiotics reduce SCFA production and may be the cause of diarrhea.10
- Fecal SCFA levels tend to be higher in obese/overweight adults than in those who are lean.24
- As an overall indicator of microbiota health status, fecal SCFA measurements, particularly n-butyrate, represent an important biomarker in identifying individuals who would benefit from prebiotic and/or probiotic therapy.25
SCFA Cut Points and Interpretation
|Analyte (µmol/g)||Low||Mildly Decreased||Optimal|
|Total SCFA||≤ 48.2||48.3 – 72.1||≥ 72.2|
|n-Butyrate||≤ 4.3||4.4 – 7.7||≥ 7.8|
|Acetate||≤ 31.4||31.5 – 46.2||≥ 46.3|
|Propionate||≤ 9.1||9.2 – 13.6||≥ 13.7|
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21. Louis P, et al. Nature Rev Microbiol 2014;12(10):661–672.
22. Qin J, et al. Nature 2012;490:55–60.
23. Guo Z, et al. Sci Rep 2016;6:20602.
24. Fernandes J, et al. Nutr Diabetes 2014;4:e121.
25. Ferrario C, et al. J Nutr 2014;144(11):1787–1796.