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 K and several B vitamins. Vitamin K and several B vitamins not only support metabolism and energy production but also bolster the immune system and enhance brain function.
This article delves into vitamin B2 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 synthesis, outlines natural strategies to promote a healthy gut for optimal vitamin production, and introduces testing options to assess vitamin synthesis and gut microbiome health.
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. [19.] 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. [19.]
Other bacterial strains known to produce vitamins include: [14.]
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. [19.]
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.
Riboflavin, also known as vitamin B2, is a water-soluble and heat-stable vitamin with many functions in the body.
It is converted into one of two coenzymes, which provide its functionality: flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), both of which are crucial for redox reactions in various metabolic pathways. Many of riboflavin’s actions occur in the mitochondria.
Riboflavin is crucial for metabolizing fats, proteins, and carbohydrates into glucose, providing the body with energy. Riboflavin supports the immune system, and promotes healthy skin and hair.
It is also integral to the metabolism of carbohydrates, fats, and proteins, contributing significantly to the body's energy production. These coenzymes act as electron carriers, particularly in the electron transport chain, which is essential for cellular energy production.
Riboflavin is also involved in the metabolism of other vitamins; for example, it aids in the conversion of tryptophan to niacin and vitamin B6 to pyridoxal 5’-phosphate.
Beyond its metabolic roles, riboflavin has antioxidant properties through its involvement in regenerating glutathione, a major cellular antioxidant.
Vitamin B2 is also vital for normal growth and development, playing a critical role during periods of rapid growth such as fetal development, reproduction, and lactation.
In the gut, riboflavin is predominantly produced by microbiota in the large intestine. Specific bacteria like Bacteroidetes, Fusobacteria, and a large proportion of Proteobacteria have the genetic capacity to synthesize riboflavin. [7.]
Additionally, Firmicutes and lactic acid bacteria from dairy products also contribute to riboflavin biosynthesis. These bacteria use guanosin-5’-triphosphate (GTP) and ribulose-5-phosphate, derived from the purine biosynthesis and pentose phosphate pathways, respectively. [7.]
The role of riboflavin extends beyond metabolism as it is crucial for the postnatal development of the gastrointestinal tract. Deficiencies in riboflavin can lead to significant changes in intestinal morphology, such as crypt hypertrophy and altered cell division, which are particularly noticeable in the duodenum and small intestine and are irreversible even after riboflavin levels are restored. [7.]
Moreover, riboflavin supplementation has been shown to influence the gut microbiome composition, increasing the abundance of riboflavin-nonproducing bacteria like Faecalibacterium prausnitzii and Roseburia spp., while decreasing the prevalence of Bacteroides in certain populations. [7.]
B vitamins play essential roles in both human and microbiome health. They function as coenzymes in numerous cellular processes including energy production, neurotransmitter synthesis and brain function, DNA synthesis and immune regulation.
These vitamins are vital for maintaining the metabolic health of the host and are also crucial for the growth and functioning of gut microbiota. B vitamins like biotin, cobalamin, and folate not only aid in energy metabolism but also influence the composition and health of the gut microbiome, promoting a symbiotic relationship between microbes and their host. [7.]
B vitamins produced in the gut help regulate the microbial ecosystem by promoting the growth of beneficial bacteria while inhibiting harmful ones, establishing a balanced gut microbiota. For instance, certain gut bacteria can synthesize B vitamins from dietary precursors, which then serve as nutrients for both the host and other microbes that lack the capabilities to produce these vitamins themselves. [20.]
This interdependence underscores the symbiotic relationship between gut bacteria and the host, emphasizing the importance of a diverse and balanced diet to maintain optimal gut health and ensure adequate vitamin synthesis.
Moreover, B vitamins have roles beyond simple nutritional support; they influence immune system function and may affect the efficacy of medications metabolized by gut bacteria.
Deficiencies in B vitamins can disrupt gut microbial balance and lead to significant health issues including impaired intestinal health and increased risk of chronic diseases. [7.]
Understanding the complex interactions between dietary B vitamins, microbial biosynthesis, and host health is essential for developing dietary strategies and treatments that support gut health and overall well-being. Such insights could lead to targeted probiotic or dietary interventions to enhance B vitamin availability and balance the gut microbiome.
The B vitamin family plays critical roles in energy production, neurotransmitter synthesis, immune regulation, detoxification, and other necessary processes. For in-depth reading on the roles and functions of specific B vitamins, please see below:
Click here for detailed information on Biotin (vitamin B7)
Click here for detailed information on Cobalamin (vitamin B12)
Click here for detailed information on Folate (vitamin B9)
Click here for detailed information on Niacin (vitamin B3)
Click here for detailed information on Pantothenic acid (vitamin B5)
Click here for detailed information on Pyridoxine (vitamin B6)
Click here for detailed information on Riboflavin (vitamin B2)
Click here for detailed information on Thiamine (vitamin B1)
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.
Blood tests are commonly utilized to assess vitamin levels in the body. These tests can measure the concentrations of specific vitamins such as 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.
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.
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 a specific B vitamin 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.
Increase Dietary Fiber: consume a variety of fiber-rich foods such as fruits, vegetables, legumes, and whole grains to feed beneficial gut bacteria. [21.]
Incorporate Fermented Foods: include foods like yogurt, kefir, sauerkraut, and kimchi in your diet to introduce beneficial probiotics to your gut. [9.]
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., 6., 9.]
Prebiotics: include prebiotic-rich foods such as onions, garlic, asparagus, and bananas that provide fuel for healthy bacteria. [15.]
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. [18.]
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. [12.]
Avoid Harmful Substances: minimize alcohol and stop smoking, as these can negatively impact gut microbiota and overall health. [10.]
Click here for examples of specialized lab testing for comprehensive nutritional assessment.
Click here for examples of specialized testing to assess microbiome health.
[1.] Bidell MR, Hobbs ALV, Lodise TP. Gut microbiome health and dysbiosis: A clinical primer. Pharmacotherapy. 2022 Nov;42(11):849-857. doi: 10.1002/phar.2731. Epub 2022 Oct 7. PMID: 36168753; PMCID: PMC9827978.
[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.] Dmitry P. Perspectives of pharmacological correction and evaluation of mitochondrial dysfunction in neurodegenerative and ischemic brain lesions. Bioactive Natural Products. Published online 2021:65-98. doi:https://doi.org/10.1016/b978-0-12-819487-4.00018-5
[5.] 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.
[6.] 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.
[7.] 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.
[8.] 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/
[9.] 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.
[10.] 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
[11.] 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
[12.] 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.
[13.] 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
[14.] 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.
[15.] 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.
[16.] 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.
[17.] Peechakara BV, Sina RE, Gupta M. Vitamin B2 (Riboflavin) [Updated 2024 Feb 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK525977/
[18.] 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.
[19.] 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
[20.] 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
[21.] 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