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Vitamin Biosynthesis
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Vitamin Biosynthesis

The human gut microbiome is an intricate and dynamic ecosystem within our bodies that has profound impacts on human health and illness.

Comprising billions of microorganisms including bacteria, viruses, fungi, and protozoa, this microbial community performs numerous functions essential to our survival. One of the lesser-known yet vital roles of these gut bacteria is their ability to synthesize various vitamins that are pivotal for maintaining bodily functions. 

A healthy gut microbiome is responsible for producing certain essential vitamins, including vitamin K2.  Vitamin K2 has essential functions in human health including calcium regulation and bone health, as well as cardiovascular and cognitive health implications.  

This article delves into the fascinating world of vitamin K2 biosynthesis by gut bacteria by identifying the specific bacteria involved, and examining the effects of gut health on this process. 

Furthermore, it discusses how disturbances in the gut microbiota can impact vitamin K2 synthesis, outlines natural strategies to promote a healthy gut for optimal vitamin K2 production, and introduces testing options to assess vitamin synthesis and gut microbiome health. 

What is Vitamin Biosynthesis?

Vitamin biosynthesis refers to the process by which living organisms, including certain bacteria in the human gut, produce vitamins that are essential for metabolic functions.

Certain gut bacteria are involved in vitamin biosynthesis, significantly impacting human health by producing essential nutrients such as vitamin K and various B vitamins. 

The biosynthesis of vitamins by the human gut microbiome is a complex and finely balanced process involving numerous bacterial species, particularly those that also produce butyrate.  [17.]  Butyrate is a short-chain fatty acid produced in the colon through the fermentation of dietary fiber by gut microbiota; butyrate is essential for maintaining intestinal health and providing energy to colonic cells.

Butyrate-producing bacteria like those from the Ruminococcaceae and Lachnospiraceae families work together to produce essential vitamins. For example, while certain bacteria such as Faecalibacterium prausnitzii and Subdoligranulum variabile can't make certain B vitamins themselves, they rely on neighboring microbes to produce these nutrients and share them, a process known as microbial cross-feeding. 

This interaction not only helps these vitamin-dependent bacteria survive but also ensures a balanced and functional gut microbiome, emphasizing the cooperative nature of our intestinal bacteria.  [17.]

Other bacterial strains known to produce vitamins include:  [13.]

Bacteroides: known for synthesizing essential nutrients like vitamin B12.

Bifidobacterium: involved in the synthesis of several B vitamins.

Enterococcus: capable of producing vitamins such as thiamine, folate, biotin, riboflavin, and pantothenic acid.

Clostridium: some species within this genus also contribute to vitamin production in the gut.

Firmicutes, Actinobacteria, and Proteobacteria: all synthesize vitamin B12  [1.]

Bacteroides fragilis, Eubacterium lentum, Enterobacter agglomerans, Serratia marcescens, and Enterococcus faecium: all produce vitamin K  [1.] 

These bacteria play a crucial role in maintaining the health and nutritional status of the host, especially under conditions where dietary intake of vitamins is insufficient.

After gut bacteria produce vitamins, these essential nutrients are released into the gut where they can be absorbed by the intestinal lining. This absorption process transports the vitamins into the bloodstream, allowing them to be distributed throughout the body where they contribute to various biological functions, such as metabolism and immune system support. This vital role underscores the importance of a healthy gut microbiome for overall wellness.

Vitamin biosynthesis by gut bacteria is influenced by several factors including the genetic makeup of the bacteria, the availability of precursors in the gut, and the overall health and diet of the host.  [17.] 

The production of these vitamins by gut bacteria not only supplements dietary intake, ensuring adequate levels within the body, but also demonstrates the integral role of the microbiome in nutritional well-being. This symbiotic relationship between humans and their gut flora highlights the potential for targeted dietary or probiotic interventions to optimize health, particularly in settings like the ICU, where patients' microbial balance can be significantly disrupted.

Vitamin K2 in Human and Microbiome Health  [4., 7., 12.]

Vitamin K2 refers to a group of compounds known as menaquinones (MQ), which are produced by bacteria in the gastrointestinal tract and also found in fermented foods. 

The distinct nature of Vitamin K2 lies in the different menaquinones, which are categorized by the length of their side chain (MK-4, MK-7, MK-9, etc.). 

These various forms have different biological activities and absorption rates, as well as different sources.

A list of all known menaquinones includes:

Menaquinone-4 (MK-4)

Menaquinone-7 (MK-7)

Menaquinone-8 (MK-8)

Menaquinone-9 (MK-9)

Menaquinone-10 (MK-10)

Menaquinone-11 (MK-11)

Menaquinone-12 (MK-12)

These different forms of vitamin K2 have varying clinical significance, with MK-4 having a shorter half-life and MK-7 demonstrating greater bioavailability and persistence in the circulation. 

Menaquinone-4 (MK-4) is synthesized in animal tissues, particularly in the liver from dietary vitamin K1. Additionally, it can be found in some animal-based foods such as meat, liver, and eggs.

Menaquinone-7 (MK-7) is primarily produced by bacteria in the gastrointestinal tract, specifically in the colon. It is also found in certain fermented foods.

While vitamin K1 is primarily involved in blood clotting, vitamin K2 is more closely associated with bone and cardiovascular health due to its role in regulating calcium metabolism and preventing arterial calcification. Also, vitamin K2 may have additional roles in human health and wellness, as emerging research indicates.  

Functions of Vitamin K2  [4., 7., 10., 12., 14.] 

Calcium Metabolism Regulation: vitamin K2 is essential for regulating calcium metabolism, facilitating the carboxylation of proteins like osteocalcin and matrix Gla protein (MGP), ensuring proper calcium deposition in bones and preventing calcification in soft tissues.

Bone Health: vitamin K2 enhances bone mineralization and density, significantly reducing the risk of osteoporosis and fractures by activating calcium-binding proteins in bones.

Cardiovascular Health: vitamin K2 helps prevent arterial calcification and maintains blood vessel elasticity by activating matrix Gla protein, reducing cardiovascular disease risks.

Anti-Inflammatory Properties: vitamin K2 exhibits anti-inflammatory effects by modulating inflammatory mediators and cytokines, enhancing immune health and reducing chronic inflammation risks.

Dental Health: vitamin K2 is associated with a lower risk of periodontal diseases due to its role in calcium metabolism.

Cancer Prevention: some studies suggest Vitamin K2 might help reduce the risk of certain cancers like breast, liver, and leukemia, though more research is needed to confirm these effects.

Neurological Health: emerging evidence suggests neuroprotective properties, supporting myelination, nerve function, and protecting against neurodegenerative diseases like Alzheimer's.

Research indicates that Vitamin K2 can mitigate the cognitive decline associated with gut dysbiosis, a condition often exacerbated by antibiotic use. This protective effect of Vitamin K2 is partly due to its ability to reduce oxidative stress and shield neurons from damage. 

Furthermore, Vitamin K2 helps restore the balance of key gut bacteria such as Lactobacillus and Bifidobacterium, which are depleted during antibiotic treatment. The restoration of these bacteria is crucial as they are directly involved in maintaining gut and brain health through the gut-brain axis.  [3.]

Gut Health: vitamin K2 influences gut microbiota composition and function, although more research is required to understand its full impact.

Impact of Gut Dysbiosis on Vitamin K2 Biosynthesis  [19.] 

Gut dysbiosis, an imbalance in the gut microbiota, can significantly disrupt the biosynthesis of essential vitamins such as B vitamins, which are crucial for maintaining health. 

The gut microbiota consists of trillions of microorganisms including bacteria, viruses, fungi, and protozoa, that play a key role in producing thousands of metabolites.  These metabolites, including B vitamins, are integral to numerous bodily functions such as energy production, neurological health, and immune response.

Dysbiosis can arise from various causes including poor diet, excessive use of antibiotics, and environmental stressors, leading to reduced diversity and an overgrowth of harmful microorganisms. This imbalance can hinder the ability of beneficial bacteria to produce essential vitamins. 

When dysbiosis occurs, the population of these vitamin-producing bacteria can be reduced, leading to decreased availability of these essential nutrients. This reduction can be exacerbated by a feedback loop where a lack of certain vitamins further impairs the growth of beneficial bacteria, leading to more pronounced dysbiosis and nutrient deficiencies.

Consequently, the lack of essential vitamins due to dysbiosis can lead to deficiencies, affecting various aspects of health. Vitamin deficiencies can impair immune function, reduce energy levels, and increase vulnerability to diseases. For example, deficiencies in B vitamins can lead to neurological disorders, anemia, and other metabolic complications. Therefore, maintaining a balanced and diverse gut microbiota is crucial for the proper synthesis of vitamins and overall health.

Testing Options for Vitamin Synthesis and Gut Health Assessment

Overview of Diagnostic Tests for Vitamin Levels (Blood Tests)

Blood tests are commonly utilized to assess vitamin levels in the body. These tests can measure the concentrations of specific vitamins such as vitamin K, vitamin A, B-complex (including B12 and folate), C, D, and E, among others. 

The process involves drawing a small amount of blood, usually from a vein in the arm, which is then analyzed in a laboratory.  Tests for Vitamin D, vitamin B12, and folate, for example, are commonly available.  

However, more comprehensive nutritional assessment panels are often offered through specialized lab companies.

Click here for examples of specialized lab testing for comprehensive nutritional assessment.  

Methods to Assess Gut Microbiome Health (Stool Tests and Microbiome Sequencing)

The health of the gut microbiome is typically assessed through stool tests and advanced microbiome sequencing techniques. Stool analysis can provide insights into the types and quantities of bacteria present in the gut, which is crucial for understanding gut health and its relationship with various diseases. 

Microbiome sequencing takes this a step further by identifying and quantifying the bacteria at a genetic level, offering a detailed view of the microbiota composition. This method can detect even minute changes in the gut environment that might affect health. 

By understanding the composition of the gut microbiota, personalized dietary recommendations and treatments can be tailored to enhance gut health and overall well-being.

Click here for examples of specialized testing to assess microbiome health.  

Interpretation of Results and When to Seek Professional Health Advice

Interpreting the results of vitamin level assessments and gut microbiome tests should be done by healthcare professionals. 

These results can sometimes be complex, involving understanding normal ranges, the implications of deviations, and potential interactions between different vitamins or gut bacteria. For example, a deficiency in vitamin K2 or an imbalance in gut microbiota might require interventions that should be managed under professional guidance. 

It is important to seek advice from healthcare providers if test results show abnormalities or if symptoms suggestive of vitamin deficiencies or gut health issues arise. This ensures that any underlying health issues can be addressed appropriately, potentially involving diet adjustments, supplementation, or other medical treatments. 

Regular check-ups and discussions with healthcare providers are recommended to monitor and maintain optimal health.

Natural Ways to Optimize Gut Microbiome Health for Optimal Vitamin Biosynthesis

Increase Dietary Fiber: consume a variety of fiber-rich foods such as fruits, vegetables, legumes, and whole grains to feed beneficial gut bacteria.  [19.] 

Incorporate Fermented Foods: include foods like yogurt, kefir, sauerkraut, and kimchi in your diet to introduce beneficial probiotics to your gut.  [8.] 

Diverse Diet: eating a wide range of foods can lead to a diverse microbiome, which is associated with better vitamin synthesis and overall health.  [1., 5., 8.]

Prebiotics: include prebiotic-rich foods such as onions, garlic, asparagus, and bananas that provide fuel for healthy bacteria.  [14.] 

Reduce Antibiotic Usage: avoid unnecessary antibiotics, as they can disrupt gut microbial balance and reduce the population of beneficial bacteria.  [1., 3.]

Limit Processed Foods and Sugars: high intakes of sugar and processed foods can promote the growth of harmful bacteria and reduce microbial diversity.  [16.] 

Regular Physical Activity: exercise can enhance the growth of beneficial gut bacteria, which can improve health and vitamin production.  [2.] 

Stress Management: reducing stress through techniques like meditation, yoga, and adequate sleep can positively affect gut health and microbial balance.  [11.] 

Avoid Harmful Substances: minimize alcohol and stop smoking, as these can negatively impact gut microbiota and overall health.  [9.] 

Order Microbiome and Nutritional Assessment Testing

Click here for examples of specialized lab testing for comprehensive nutritional assessment.  

Click here for examples of specialized testing to assess microbiome health.  

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See References

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[2.] Boytar AN, Skinner TL, Wallen RE, Jenkins DG, Dekker Nitert M. The Effect of Exercise Prescription on the Human Gut Microbiota and Comparison between Clinical and Apparently Healthy Populations: A Systematic Review. Nutrients. 2023 Mar 22;15(6):1534. doi: 10.3390/nu15061534. PMID: 36986264; PMCID: PMC10054511. 

[3.] Chatterjee K, Mazumder PM, Sarkar SR, et al. Neuroprotective effect of Vitamin K2 against gut dysbiosis associated cognitive decline. Physiology & Behavior. 2023;269:114252. doi:https://doi.org/10.1016/j.physbeh.2023.114252 

[4.] Halder M, Petsophonsakul P, Akbulut AC, Pavlic A, Bohan F, Anderson E, Maresz K, Kramann R, Schurgers L. Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease. Int J Mol Sci. 2019 Feb 19;20(4):896. doi: 10.3390/ijms20040896. PMID: 30791399; PMCID: PMC6413124.

[5.] Heiman ML, Greenway FL. A healthy gastrointestinal microbiome is dependent on dietary diversity. Mol Metab. 2016 Mar 5;5(5):317-320. doi: 10.1016/j.molmet.2016.02.005. PMID: 27110483; PMCID: PMC4837298. 

[6.] Hossain KS, Amarasena S, Mayengbam S. B Vitamins and Their Roles in Gut Health. Microorganisms. 2022 Jun 7;10(6):1168. doi: 10.3390/microorganisms10061168. PMID: 35744686; PMCID: PMC9227236. 

[7.] Imbrescia K, Moszczynski Z. Vitamin K. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551578/   

[8.] Leeuwendaal NK, Stanton C, O'Toole PW, Beresford TP. Fermented Foods, Health and the Gut Microbiome. Nutrients. 2022 Apr 6;14(7):1527. doi: 10.3390/nu14071527. PMID: 35406140; PMCID: PMC9003261. 

[9.] Lin R, Zhang Y, Chen L, et al. The effects of cigarettes and alcohol on intestinal microbiota in healthy men. Journal of Microbiology. 2020;58(11):926-937. doi:https://doi.org/10.1007/s12275-020-0006-7 

[10.] Ma M, Ma Z, He Y, et al. Efficacy of vitamin K2 in the prevention and treatment of postmenopausal osteoporosis: A systematic review and meta-analysis of randomized controlled trials. Frontiers in Public Health. 2022;10. doi:https://doi.org/10.3389/fpubh.2022.979649

[11.] Madison A, Kiecolt-Glaser JK. Stress, depression, diet, and the gut microbiota: human-bacteria interactions at the core of psychoneuroimmunology and nutrition. Curr Opin Behav Sci. 2019 Aug;28:105-110. doi: 10.1016/j.cobeha.2019.01.011. Epub 2019 Mar 25. PMID: 32395568; PMCID: PMC7213601. 

[12.] Mladěnka P, Macáková K, Kujovská Krčmová L, et al. Vitamin K – sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity. Nutrition Reviews. 2021;80(4). doi:https://doi.org/10.1093/nutrit/nuab061 

[13.] Morowitz MJ, Carlisle EM, Alverdy JC. Contributions of intestinal bacteria to nutrition and metabolism in the critically ill. Surg Clin North Am. 2011 Aug;91(4):771-85, viii. doi: 10.1016/j.suc.2011.05.001. PMID: 21787967; PMCID: PMC3144392.

[14.] Olszewska-Czyz I, Firkova E. A Case Control Study Evaluating the Relationship between Vitamin K2 Serum Level and Periodontitis. Healthcare (Basel). 2023 Nov 10;11(22):2937. doi: 10.3390/healthcare11222937. PMID: 37998429; PMCID: PMC10670967. 

[15.] Oniszczuk A, Oniszczuk T, Gancarz M, Szymańska J. Role of Gut Microbiota, Probiotics and Prebiotics in the Cardiovascular Diseases. Molecules. 2021 Feb 22;26(4):1172. doi: 10.3390/molecules26041172. PMID: 33671813; PMCID: PMC7926819. 

[16.] Shi Z. Gut Microbiota: An Important Link between Western Diet and Chronic Diseases. Nutrients. 2019 Sep 24;11(10):2287. doi: 10.3390/nu11102287. PMID: 31554269; PMCID: PMC6835660. 

[17.] Soto-Martin EC, Warnke I, Farquharson FM, et al. Vitamin Biosynthesis by Human Gut Butyrate-Producing Bacteria and Cross-Feeding in Synthetic Microbial Communities. Relman DA, ed. mBio. 2020;11(4). doi:https://doi.org/10.1128/mbio.00886-20 

[18.] Uebanso T, Shimohata T, Mawatari K, Takahashi A. Functional Roles of B‐Vitamins in the Gut and Gut Microbiome. Molecular Nutrition & Food Research. 2020;64(18):2000426. doi:https://doi.org/10.1002/mnfr.202000426 

[19.] Valdes AM, Walter J, Segal E, Spector TD. Role of the Gut Microbiota in Nutrition and Health. BMJ. 2018;361(361):k2179. doi:https://doi.org/10.1136/bmj.k2179

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