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16-OH-E1 %
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16-OH-E1 %

The Firmicutes/Bacteroidetes (F/B) ratio is a significant measure in understanding gut microbiota composition and its impact on health.  

Bacteroidetes, a major phylum of gram-negative bacteria, make up about 30% of the human gut microbiota and play a crucial role in maintaining gut homeostasis. They degrade complex polysaccharides from dietary fibers, producing short-chain fatty acids (SCFAs) that serve as energy sources and regulate immune function. 

Firmicutes, another dominant phylum, consist primarily of gram-positive bacteria involved in fermenting complex carbohydrates and producing SCFAs like butyrate, acetate, and propionate, which support intestinal barrier function and regulate immune responses.

An imbalance in the F/B ratio has been linked to various health conditions including obesity, type 2 diabetes, and cardiovascular diseases.  While obese individuals often have a higher F/B ratio, the relationship between the F/B ratio and health outcomes remains complex and sometimes controversial due to factors like diet, antibiotic use, and physical activity influencing microbiota composition. 

Laboratory testing for the F/B ratio involves analyzing stool samples using advanced molecular techniques to provide accurate quantification of Bacteroidetes and Firmicutes.  

Although the F/B ratio offers valuable insights, it is essential to consider the complex interactions of specific bacterial species and other factors influencing gut health for a comprehensive understanding.

Microbiological Background of Bacteroidetes  [3., 6., 9., 10., 14.] 

Bacteroidetes, a significant phylum of gram-negative bacteria, play a crucial role in maintaining gut homeostasis. They make up about 30% of the human gut microbiota, with variations based on population, geography, age, and diet.

This phylum includes several genera, notably Bacteroides, which are non-spore-forming, anaerobic, rod-shaped bacteria, and Prevotella.  Among the 24 identified species, Bacteroides fragilis and B. thetaiotaomicron are the most studied. 

These bacteria inhabit the mucosal surfaces of the gastrointestinal tract, where they degrade complex polysaccharides from dietary fibers and mucins, contributing significantly to gut health.

Bacteroidetes enhance the host's fitness by fermenting dietary fibers and producing short-chain fatty acids (SCFAs) like acetate, propionate, and butyrate, which serve as energy sources for host epithelial cells and regulate immune function. 

They maintain gut barrier integrity, modulate host metabolism, and protect against pathogenic colonization by competing for nutrients and producing antimicrobial compounds.  Alterations in Bacteroidetes abundance have been linked to various gastrointestinal disorders, metabolic diseases, and immune-related conditions. 

Maintaining a balanced ratio of Bacteroidetes to other phyla, such as Firmicutes, is essential for gut health and disease prevention. 

Modulating Bacteroidetes levels through approaches like fecal microbiota transplantation (FMT) and microbiota modulation are being explored as therapeutic strategies for conditions like C. difficile infection, diabetes, and inflammatory bowel diseases (IBD).

Microbiological Background of Firmicutes  [7., 8., 9.] 

Firmicutes is a major phylum of bacteria that are prevalent in the human gut microbiome. It is one of the two dominant phyla found in the gut, along with Bacteroidetes.

Taxonomically, Firmicutes is a phylum of Gram-positive bacteria that includes a diverse range of species, many of which are anaerobic or facultatively anaerobic.  Some notable families within this phylum are Clostridiaceae, Lactobacillaceae, Ruminococcaceae, and Lachnospiraceae.

Members of Firmicutes play crucial roles in the gut microbiome, such as the fermentation of complex carbohydrates and the production of short-chain fatty acids (SCFAs) like butyrate, acetate, and propionate.  

These SCFAs have various beneficial effects on host physiology including maintaining intestinal barrier function, regulating immune responses, and providing energy sources for colonocytes.

The abundance and diversity of Firmicutes in the gut microbiome have been associated with various health outcomes.  An imbalance in the ratio of Firmicutes to Bacteroidetes has been linked to obesity and metabolic dysfunction, with a higher Firmicutes/Bacteroidetes ratio observed in obese individuals compared to lean individuals.  

However, this association remains controversial, and more recent studies suggest that the overall microbial richness and specific bacterial species may be more relevant than the phylum-level ratio.   

Additionally, certain Firmicutes species such as Faecalibacterium prausnitzii have been shown to exhibit anti-inflammatory properties and are associated with a reduced risk of inflammatory bowel diseases.

Understanding the Firmicutes/Bacteroidetes Ratio  [9., 13., 15.] 

The gut microbiota, particularly the ratio of Firmicutes to Bacteroidetes (F/B), has been suggested as a potential biomarker for obesity, type 2 diabetes, and cardiovascular diseases.  This ratio has also been associated with BPH and prostate disease, breast cancer, and gestational diabetes.  [2.]

Research indicates that obese individuals often have a higher F/B ratio compared to those with normal weight, suggesting its potential as a hallmark of obesity. 

However, the relationship between the F/B ratio and health status is inconsistent, with many studies reporting conflicting results.  These discrepancies are likely due to methodological differences in sample processing, DNA sequencing, and a lack of consideration for lifestyle factors that affect microbiota composition.

Despite early findings suggesting that a higher F/B ratio is associated with increased energy extraction and weight gain, recent studies have shown that this ratio is not a reliable indicator of obesity. 

Variations in gut microbiota composition are influenced by factors such as diet, antibiotic use, and physical activity, making it difficult to establish a direct link between the F/B ratio and obesity.  

Furthermore, the F/B ratio does not consistently correlate with metabolic health markers or short-chain fatty acid production, complicating its use as a biomarker. 

However, studies have shown that the composition of gut microbiota changes significantly throughout life.  In a study involving 1,550 healthy participants from Ukraine, the relative abundance of Firmicutes increased, while Bacteroidetes decreased with age.  [15.]

Consequently, the Firmicutes/Bacteroidetes ratio significantly increased from childhood to old age.  The odds of having an F/B ratio greater than 1 also increased with age, reaching the highest values in the 60-69 year age group.

These findings highlight that the composition of gut microbiota, particularly the F/B ratio, changes significantly across different age groups. While the F/B ratio tends to increase with age, this pattern may reverse in very old age. 

Such age-related changes in gut microbiota composition could contribute to the understanding of the mechanisms underlying aging and its associated health conditions. 

To better understand the role of gut microbiota in obesity, future research should focus on identifying specific microbial signatures and consider the influence of various lifestyle factors.

Laboratory Testing for Firmicutes/Bacteroidetes Ratio

Laboratory Testing, Sample Requirements, and Preparation

Bacteroidetes and Firmicutes abundance in the gut microbiota, and their associated ratio, are assessed in stool samples.  Stool samples may be collected from the comfort of home.  

Testing may require avoidance of certain medications and/or supplements including probiotics prior to sample collection.  It is important to consult with the ordering provider for full test preparation instructions.

Importance of Culture-Independent Molecular Techniques

Molecular techniques offer advantages in terms of sensitivity, specificity, and the ability to detect diverse microbial communities.  

Polymerase chain reaction (PCR) and quantitative PCR (qPCR) assays can target specific regions of the bacterial genome, allowing for the rapid and accurate quantification of Bacteroidetes and Firmicutes in clinical samples. 

Additionally, next-generation sequencing (NGS) techniques, such as 16S rRNA gene sequencing and metagenomic shotgun sequencing, provide a comprehensive analysis of the gut microbiota composition, enabling the quantification of Bacteroidetes and Firmicutes abundance at the species or strain level.

Interpretation of Test Results

Optimal Firmicutes/Bacteroidetes Ratio

It is important to consult with the laboratory company used for test interpretation.  

One lab company recommends a Firmicutes/Bacteroidetes ratio of <1.  [11.]

Clinical Significance of an Elevated Firmicutes/Bacteroidetes Ratio 

An elevated Firmicutes/Bacteroidetes (F/B) ratio in the gut microbiome has been associated with several clinical conditions, suggesting its potential as a biomarker and therapeutic target.  

A higher F/B ratio has been linked to obesity, metabolic disorders, BPH and inflammation.  [2., 5., 13.] 

However, some studies and systematic reviews fail to show a corroboration between a higher F/B ratio and obesity or metabolic disorders, or show conflicting results.  [4., 7.] 

Microbiome health is clearly an important part of overall human health.  [1.]  While the F/B ratio provides a broad overview of gut microbiome composition, it is essential to consider the complex interactions and functional roles of specific bacterial species within these phyla, as well as other factors that shape the gut microbiome.

Results should also be interpreted within the context of the individual’s comprehensive health history.  

Clinical Significance of a Low Firmicutes/Bacteroidetes Ratio

A low Firmicutes/Bacteroidetes (F/B) ratio in the gut microbiome has been associated with several clinical conditions.  Studies have linked a decreased F/B ratio to inflammatory bowel diseases (IBD), indicating a state of gut dysbiosis and chronic inflammation.  [12.] 

Additionally, a low F/B ratio has been observed in patients with NASH or non-alcoholic steatohepatitis, also known as NAFLD, non-alcoholic fatty liver disease.  [2.]

While the F/B ratio provides a broad overview of gut microbiome composition, it is crucial to consider the complex interactions and functional roles of specific bacterial species within these phyla, as well as other factors that shape the gut microbiome.

Individual variations in diet, lifestyle, genetics, and environmental factors also contribute to differences in microbial composition and may influence the optimal range of the Firmicutes/Bacteroidetes ratio.

Related Biomarkers to Test

In addition to the Firmicutes/Bacteroidetes ratio, several other biomarkers are relevant for assessing microbiota composition and gut health. 

Comparison with Other Gut Microbiota and Microbial Markers

The Firmicutes/Bacteroidetes ratio is just one aspect of gut microbiota composition that can be assessed in clinical samples.  Comparing its abundance and diversity with other microbial markers such as Proteobacteria, Actinobacteria, and Verrucomicrobia provides a more comprehensive understanding of gut dysbiosis and its implications for human health. 

Changes in the relative abundance of these microbial taxa have been associated with various metabolic disorders, inflammatory conditions, and gastrointestinal diseases, underscoring the importance of considering multiple biomarkers in microbiota analysis.

Integration of Firmicutes/Bacteroidetes Ratio with Markers of Digestive Function

Increasingly, lab companies are offering comprehensive assessments of the microbiome in conjunction with markers of digestive health and inflammation, which can provide a broad assessment of gut health.  

Digestive function markers may include pancreatic enzymes such as elastase, as well as assessments of fat and proteins present in stool.  Markers of digestive inflammation including calprotectin and Eosinophil Protein X may also be considered.  

Finally, the biomarker zonulin may also be assessed in stool samples to assess for a leaky gut process.  

Combining markers of digestive health and inflammation along with a comprehensive microbiome analysis can provide a comprehensive assessment of digestive function.  

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What's 
16-OH-E1 %
?
16-OH-E1, also known as 16-alpha hydroxyestrone, is a type of estrogen metabolite. Estrogen metabolites are essentially byproducts created when your body processes estrogen, a hormone that plays a vital role in both female and male bodies. In women, it's responsible for the development and regulation of the female reproductive system and secondary sex characteristics. In men, it helps regulate libido and erectile function. The "16-OH" refers to the specific way this metabolite is formed in the body. It's one of three pathways your body can use to metabolize estrogen, each resulting in a different metabolite. The "%" part refers to the proportion of this particular metabolite compared to the total amount of estrogen metabolites in your body. In essence, 16-OH-E1 % gives us a snapshot of how your body is processing estrogen.
If Your Levels Are High
High levels of 16-OH-E1 % could indicate that your body is metabolizing estrogen in a specific way that results in more of this particular metabolite. This could be due to a variety of factors, including genetic predispositions, lifestyle factors, or certain medications. For instance, some drugs, such as those used in hormone replacement therapy or certain types of birth control, can influence how your body processes estrogen. Additionally, conditions like obesity or insulin resistance can also affect estrogen metabolism. It's important to note that while high levels of 16-OH-E1 % can provide insight into your hormonal health, it doesn't necessarily mean there's a problem. It's just one piece of the puzzle and should be considered in the context of other hormonal and health markers.
Symptoms of High Levels
Symptoms of high levels of 16-OH-E1 % could include hormonal imbalances, changes in menstrual cycle for women, and changes in libido or erectile function in men.
If Your Levels are Low
Low levels of 16-OH-E1 % could indicate that your body is not metabolizing estrogen via the 16-alpha hydroxyestrone pathway as much as it typically should. This could be due to a variety of factors, including genetic predispositions, age, or external influences such as certain medications like Tamoxifen, which is known to affect estrogen metabolism. It could also be associated with conditions that impact hormone levels or metabolism, such as hypothyroidism or liver disease. However, it's important to note that having a low 16-OH-E1 % doesn't necessarily mean there's a problem, as everyone's body processes hormones slightly differently. It's just one piece of the larger picture of your hormonal health.
Symptoms of Low Levels
Symptoms of low levels of 16-OH-E1 % could include decreased libido, irregular menstrual cycles in women, and potential difficulties with erectile function in men.
See References

[1.] Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev. 2023 Jan 11;123(1):31-72. doi: 10.1021/acs.chemrev.2c00431. Epub 2022 Nov 1. PMID: 36317983; PMCID: PMC9837825.

[2.] An J, Kwon H, Young Han Kim. The Firmicutes/Bacteroidetes Ratio as a Risk Factor of Breast Cancer. Journal of Clinical Medicine. 2023;12(6):2216-2216. doi:https://doi.org/10.3390/jcm12062216

[3.] Bacteroidetes: The Jekyll and Hyde of the Human Gut Microbiome. Pharmacy Times. https://www.pharmacytimes.com/view/bacteroidetes-the-jekyll-and-hyde-of-the-human-gut-microbiome

[4.] Firmicutes/Bacteroidetes Ratio of Gut Microbiota and Its Relationships with Clinical Parameters of Type 2 Diabetes Mellitus: A Systematic Review | Open Access Macedonian Journal of Medical Sciences. oamjmseu. Published online August 7, 2023. https://oamjms.eu/index.php/mjms/article/view/10478

[5.] Hassan, N.E., El Shebini, S.M., El-Masry, S.A. et al. Brief overview of dietary intake, some types of gut microbiota, metabolic markers and research opportunities in sample of Egyptian women. Sci Rep 12, 17291 (2022). https://doi.org/10.1038/s41598-022-21056-z

[6.] Hou, K., Wu, ZX., Chen, XY. et al. Microbiota in health and diseases. Sig Transduct Target Ther 7, 135 (2022). https://doi.org/10.1038/s41392-022-00974-4

[7.] Houtman, T.A., Eckermann, H.A., Smidt, H. et al. Gut microbiota and BMI throughout childhood: the role of firmicutes, bacteroidetes, and short-chain fatty acid producers. Sci Rep 12, 3140 (2022). https://doi.org/10.1038/s41598-022-07176-6

[8.] Huang Y, Shi X, Li Z, Shen Y, Shi X, Wang L, Li G, Yuan Y, Wang J, Zhang Y, Zhao L, Zhang M, Kang Y, Liang Y. Possible association of Firmicutes in the gut microbiota of patients with major depressive disorder. Neuropsychiatr Dis Treat. 2018 Dec 3;14:3329-3337. doi: 10.2147/NDT.S188340. PMID: 30584306; PMCID: PMC6284853.

[9.] Magne F, Gotteland M, Gauthier L, Zazueta A, Pesoa S, Navarrete P, Balamurugan R. The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? Nutrients. 2020 May 19;12(5):1474. doi: 10.3390/nu12051474. PMID: 32438689; PMCID: PMC7285218.

[10.] Pant A, Das B. Microbiome-based therapeutics: Opportunity and challenges. Progress in molecular biology and translational science. Published online January 1, 2022:229-262. doi:https://doi.org/10.1016/bs.pmbts.2022.07.006

[11.] Rupa Health.  1.GI-MAP + Zonulin Sample Report.pdf. Google Docs. https://drive.google.com/file/d/13LXmPBhXV2Y9paOeE5id2OM2X0V5gJ56/view 

[12.] Stojanov S, Berlec A, Štrukelj B. The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms. 2020 Nov 1;8(11):1715. doi: 10.3390/microorganisms8111715. PMID: 33139627; PMCID: PMC7692443.

[13.] Takezawa K, Fujita K, Matsushita M, et al. The Firmicutes/Bacteroidetes ratio of the human gut microbiota is associated with prostate enlargement. The Prostate. Published online September 13, 2021. doi:https://doi.org/10.1002/pros.24223

[14.] Thomas F, Hehemann JH, Rebuffet E, Czjzek M, Michel G. Environmental and gut bacteroidetes: the food connection. Front Microbiol. 2011 May 30;2:93. doi: 10.3389/fmicb.2011.00093. PMID: 21747801; PMCID: PMC3129010.

[15.] Vaiserman, A., Romanenko, M., Piven, L. et al. Differences in the gut Firmicutes to Bacteroidetes ratio across age groups in healthy Ukrainian population. BMC Microbiol 20, 221 (2020). https://doi.org/10.1186/s12866-020-01903-7

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16-OH-E1 %

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