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B Vitamins and Their Roles in Gut Health

Department of Biochemistry, Memorial University of Newfoundland, St. John’s, NL A1C 5S7, Canada
Author to whom correspondence should be addressed.
Microorganisms 2022, 10(6), 1168;
Received: 4 May 2022 / Revised: 2 June 2022 / Accepted: 4 June 2022 / Published: 7 June 2022
(This article belongs to the Special Issue The Role of the Gut Microbiota in Human Health and Disease)


B vitamins act as coenzymes in a myriad of cellular reactions. These include energy production, methyl donor generation, neurotransmitter synthesis, and immune functions. Due to the ubiquitous roles of these vitamins, their deficiencies significantly affect the host’s metabolism. Recently, novel roles of B vitamins in the homeostasis of gut microbial ecology and intestinal health continue to be unravelled. This review focuses on the functional roles and biosynthesis of B vitamins and how these vitamins influence the growth and proliferation of the gut microbiota. We have identified the gut bacteria that can produce vitamins, and their biosynthetic mechanisms are presented. The effects of B vitamin deficiencies on intestinal morphology, inflammation, and its effects on intestinal disorders are also discussed.

1. Introduction

B vitamins are a group of water-soluble organic compounds essential for several physiological functions of almost all living organisms [1]. The functional roles of these micronutrients are diverse, and they primarily act as cofactors in a plethora of enzymatic reactions. One or more B vitamins are involved in every energy-producing reaction of the cells, such as the mitochondrial citric acid cycle and cellular aerobic respiration [2]. They also play vital roles in immune functions, neurotransmitter synthesis, one-carbon metabolism, cell signalling, and even nucleic acid biosynthesis [3,4,5]. For instance, coenzyme A, an active form of vitamin B5, is a ubiquitous molecule in the cells and acts as a cofactor or direct precursor for numerous cellular intermediates [6,7].
Our gut is one of the most significant parts of the body. It acts as a way to transit and absorb what we eat [8]. It hosts different types of microorganisms such as bacteria, eukarya, and archaea. These microorganisms are commonly known as the “gut microbiota.” They comprise Bacteroidetes and Firmicutes as the dominant phyla and Actinobacteria, Proteobacteria, and Verrucomicrobia as minority members [9,10]. They maintain a symbiotic relationship with the host and protect against harmful pathogens [11]. They enhance energy utilization through intestinal fermentation [12] and regulate host immune function and signalling molecules [13]. The human gut microbiota is unique and relatively stable, and thus highly resilient to change [14]. In spite of this, they are also dynamic, and their composition is remodelled during different stages of our lifespan [15]. Several factors, such as the birth method of a child [16,17]; the age of the host [18]; lifestyle; medications; and, most importantly, diet [19,20,21], significantly modulate the composition of the gut microbiota.
Nevertheless, our gut also harbours bacteria that produce B vitamins, including biotin, cobalamin, folate, niacin, pantothenate, pyridoxine, riboflavin, and thiamin, but in limited amounts [22]. Several gut bacteria require specific vitamins for their growth, and at the same time, auxotrophic bacteria create competition between them. Deficiencies of such vitamins impair normal cellular metabolism and instigate the development of several chronic diseases in humans. Therefore, B vitamins are essential not only for the host but also for the bacteria living in the gut. A dietary supply of these vitamins is essential to meet the host’s daily requirements. B vitamins play crucial roles in shaping the diversity and richness of the gut microbiota. Considerable evidence has demonstrated that a healthy gut lies in a healthy microbial ecology. Therefore, it is indispensable to segregate the relationship between gut microbiota and a healthy gut. This review highlights the functions and effects of each B vitamin, the bacteria that can synthesize these vitamins, and how they influence the growth and proliferation of the gut microbiota and the overall intestinal health.

2. Vitamin B1/Thiamin

Thiamin is an essential cofactor required for several enzymes, especially in glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway [23,24]. Several bacteria can synthesize free thiamine or its active form, thiamine pyrophosphate (TPP) [25]. However, bacteria belonging to the enterotype 2 class have higher thiamine biosynthetic capacity [10]. This class of bacteria, mainly Prevotella and Desulfovibrio, is overexpressed with four enzymes—hydroxymethylpyridine kinase, phosphomethylpyridine kinase, thiamine-phosphate pyrophosphorylase, and thiamine-monophosphate kinase—crucial for thiamin biosynthesis [10]. Additionally, more than 90% of other gut-associated Bacteroides possess the ability for thiamin biosynthesis and the thiamin transporter genes [26]. Dietary free thiamine is absorbed through carrier-mediated transportation such as high-affinity thiamin transporter 1 (THTR-1) and 2 (THTR-2) located in the epithelium and mucosa of the small intestine [23,27]. If the dietary thiamine is in the bound form, such as TPP, they have to be first converted to free thiamin before it is absorbed. Likewise, the above transporters, i.e., THTR-1 and THTR_2, are primarily responsible for the absorption of bacterially produced free thiamin in the colon [25]. However, TPP produced by gut microbiota is absorbed directly by TPP transporters such as TPPT -1 [28], indicating a difference in dietary and bacterially produced TPP absorption. Although the role of thiamine on intestinal integrity is not well understood, some have suggested having certain gut-related immune regulatory functions through a recent concept involving energy metabolism. Mathis and Shoelson suggested that thiamine directs the energy balance between glycolysis and TCA cycle activities, controlling immunometabolism [29]. It is also likely to have some roles associated with intestinal-linked immune cells. It has been shown that thiamine deficiency reduces the abundance of the Payer’s patches and decreases the size of B-cell follicles, leading to a reduction in naïve B cells in female Balb/c mice [30]. Their findings indicated a potential gut-related role of thiamine in immunometabolism.

3. Vitamin B2/Riboflavin

Riboflavin is another micronutrient involved in the energy-producing reactions of carbohydrate, fat, and protein metabolisms [24]. Riboflavin is converted to its active forms, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), by flavokinase and FAD synthetase, respectively. Human gut microbiota can produce riboflavin, primarily in the large intestine [25]. Dietary riboflavin ingested in FAD or FMN forms must be converted into free riboflavin before absorption [31,32]. In humans, riboflavin absorption occurs mainly in the proximal small intestine through active carrier-mediated transportation [33]. A complete riboflavin operon is present in all Baceteroidetes and Fusobacteria, as well as in 92% of Proteobacteria [34], indicating they are the primary riboflavin producers in the gut. In addition, half of the Firmicutes are predicted to be riboflavin producers [34]. Lactic acid bacteria from dairy products also possess riboflavin biosynthesis capacity [35]. These bacteria synthesize riboflavin by utilizing guanosin-5’-triphosphate (GTP), a compound derived from the purine biosynthesis pathway, and ribulose-5-phosphate, an intermediate from the pentose phosphate pathway [36].
Interestingly, riboflavin is also required for the postnatal development of the gastrointestinal tract. Its deficiency was associated with crypt hypertrophy, interruptions in crypt bifurcation in rats [37,38], and loss of proliferative potentials in intestinal cells [39]. These changes were seen in the postnatal and post-weaning stages [38]. The changes were irreversible even after the repletion of riboflavin in both in vivo [40] and in vitro experiments [39]. Williams and colleagues have shown that riboflavin deficiency reduced villus number but increased its length [41,42]. Riboflavin depletion in humans was also associated with shorter duodenal crypt and low cell division [43]. In vitro studies using Caco-2, HCT116, and HT29 cells demonstrated potential mechanisms of riboflavin deficiency phenotype. They include inhibiting cell growth by reducing cellular ATP generation and elevating oxidative stress [39], defective mitosis, and accumulation of aneuploidy cells [43]. The changes in this intestinal morphology might also be related to its adaptive responses to deficiency-related stresses [42]. On the other hand, riboflavin supplementation increased the abundance of bacteria that cannot synthesize riboflavin, such as Faecalibacterium prausnitzii and Roseburia spp. [33]. Higher intake was also associated with an increase in the abundance of Prevotella spp. but Bacteroides’ concentration was decreased in lactating women [44].

4. Vitamin B3/Niacin

Vitamin B3, known as nicotinamide, nicotinic acid, or niacin, is converted into its active form, nicotinamide adenine dinucleotide (NAD), which is essential for many critical metabolic processes, primarily as a redox cofactor [45]. Similar to other higher organisms, intestinal bacteria synthesize vitamin B3 mainly from amino acid tryptophan but using a unique pathway [46,47]. According to the genetic assessment, the Bacilli class contains only 4, the Clostridia class contains 44, and Proteobacteria contains 29 potential niacin synthesizing bacteria [34]. Bacteroides fragilis, Prevotella copri, and Ruminococcus lactaris can also produce vitamin B3 in the gut as they possess a vitamin B3 biosynthesis pathway [34,48]. Moreover, niacin-responsive transcription factor NiaR (YrxA) is present in a diverse group of Bacillus and Clostridium bacteria, meaning they can undergo de novo synthesis of NAD [49,50]. The human and mouse colonic epithelial cells possess an efficient, specific, and regulated mechanism for the uptake of vitamin B3. The bacterially synthesized vitamin B3 contributes to local colonocyte nutrition and maintains the morphology of intestinal stem cells [51].
A study from the FoCus cohort identified links between vitamin B3 and intestinal microbial composition [52]. They found a significant association between vitamin B3 deficiency and low α-diversity and the abundance of Bacteroidetes in obese individuals [52]. The abundance of this bacteria was significantly higher during a gut-targeted delayed-release of nicotinic acid but not the nicotinamide in those obese subjects [52]. Qi and colleagues isolated intestinal crypt cells from a C3H/HeN conventionally raised mouse and treated them with vitamin B3. Vitamin B3 treatment with 1200 ug/mL significantly increased the growth rate of organoids [45]. Vitamin B3 plays a vital role in reducing inflammation and causes relapsing inflammatory bowel diseases such as ulcerative colitis when deficient. It controls inflammation by inhibiting vascular permeability in intestinal tissues by activating the PGD2/DP1 signal in endothelial cells [53]. It also modulated the inflammatory response by enhancing the rate of ATP generation in Caco-2 cells [54]. Interestingly, vitamin B3 engages in various metabolic reactions that alter the cellular redox state and rapamycin signalling pathway [51], thus suppressing the colon’s inflammations [53].
Furthermore, vitamin B3 protects colonic epithelial cells against the dextran-sulfate-sodium (DSS)-induced apoptosis and promotes cell proliferation in mice. It maintains the intestinal epithelium barrier by activating the D prostanoid 1 (DP1) receptor in macrophages and endothelial and colonic epithelial cells [53]. Lower plasma niacin levels have been observed in patients with Crohn’s disease [55]. Interestingly, retention enema containing vitamin B3 effectively promoted mucosal healing in patients with ulcerative colitis, most likely due to the downregulation of colonic inflammatory cytokines and suppression of proinflammatory gene expression [53]. In another in vitro study, cellular metabolites such as glutamine, isoleucine, ornithine, and glycerophosphocholine were downregulated, and glutamic acid was upregulated in inflamed Caco-2 cells. The impairments in the metabolite profile were ameliorated with the addition of vitamin B3 [54], which means that the therapeutic properties of vitamin B3 might be related to improving specific cellular metabolites that were impaired during acute inflammations.

5. Vitamin B5/Pantothenic Acid

Vitamin B5, or pantothenic acid, is an essential precursor of coenzyme A (CoA) and acts as an acyl-carrier protein [56]. It is involved in various metabolic pathways such as the citric acid cycle, cell growth, neurotransmitter synthesis, and fatty acid oxidation [1,57,58]. Various bacteria, including Escherichia coli, Salmonella typhimurium, and Corynebacterium glutamicum, can synthesize vitamin B5. They use aspartate and intermediate metabolites of valine biosynthesis to produce vitamin B5 [59,60,61]. For instance, S. Typhimurium produces pantothenate from α-ketoisovalerate using acetohydroxy acid synthase isozyme I and dihydroxy acid dehydratase enzymes [62]. Moreover, other bacteria, such as Lactobacillus helveticus, require pantothenic acid for their fatty acid and biotin metabolism [63]. Dietary pantothenic acid supplementation also influences gut microbial profile. Enhanced pantothenic acid intake increased the relative abundance of Prevotella and Actinobacteria and decreased the abundance of Bacteroides in lactating women [44].

6. Vitamin B6/Pyridoxine

Vitamin B6 has six vitamers, namely, pyridoxine (PN); pyridoxal (PL); pyridoxamine (PM); and their phosphorylated forms, i.e., pyridoxal phosphate (PLP), pyridoxine phosphate (PNP), and pyridoxamine phosphate (PMP) [64]. PLP is the enzymatically most active form of vitamin B6. Vitamin B6 acts as a cofactor for many biochemical reactions, primarily involved in amino acid biosynthesis and catabolism. Besides this, it is involved in fatty acid and neurotransmitter biosynthesis and also acts as an antioxidant [65,66,67,68]. In the mammalian gut, bacteria synthesize vitamin B6 through de novo or salvage pathways. Microbes such as Bacteroides fragilis and Prevotella copri (Bacteroidetes), Bifidobacterium longum and Collinsella aerofaciens (Actinobacteria), and Helicobacter pylori (Proteobacteria) can produce vitamin B6 as they have these biosynthetic mechanisms [69].
Most dietary vitamins are absorbed in the small intestine; however, uptake of a certain amount of dietary and bacterially synthesized vitamin B6 still occurs in the large intestine [65] because many vitamin B6 transporters are also expressed in the mammalian colon [22]. Vitamin B6 auxotrophic prokaryotes and single-cell eukaryotes rely on importing this vitamin from their surroundings, while multicellular organisms transport it to different host organs after absorption [65]. Vitamin B6 produced in the gut is not sufficient for the host’s daily requirements. Its deficiency reduced microbial β-diversity and significantly altered intestinal metabolite compared to the control groups in rats [70]. An abundance of Lachnospiraceae_NK4A136_group [70] and Prevotella [44] were elevated with vitamin B6 deficiency, while the abundance of Bacteroides was decreased when the vitamin B6 intake was high [44]. Moreover, Bifidobacterium, Slackia, Enterococcus, Thiococcus, Klebsiella, Serratia, and Enterobacter abundances were also decreased with vitamin B6 supplementation in lactose-intolerant patients [71].
A cross-sectional study has shown an association of severity of irritable bowel disease symptoms with low dietary vitamin B6 intake [72]. A plausible explanation includes the trigger of inflammation by shifting the balance between anti-inflammatory to proinflammatory cytokines with low vitamin B6 [72]. The presence of a P2X receptor antagonist such as pyridoxal phosphate 6-azophenyl-2,4-disulfonic acid, a derivative of vitamin B6 [72], and impairment in microbiota-related intestinal metabolites such as short-chain fatty acids [70] might play a significant role in triggering inflammation. Recently, Yin and colleagues demonstrated that dietary supplementation of vitamin B6 downregulated the inflammatory cytokines and upregulated the mRNA expression of amino acid transporters in the jejunum of weaned piglets [73]. Moreover, vitamin B6 deprivation studies on aquatic animals have shown a significant decrease in the number of mucous-secreting cells, a critical factor in maintaining gut health [74]. Nevertheless, vitamin B6 deficiency did not alter the basic morphological features of enterocytes, such as cell viability, cell volume, membrane permeability, and protein content in rats, but decreased calcium transport flux [75].

7. Vitamin B7/Biotin

Vitamin B7 acts as a coenzyme for several biochemical reactions, such as glycolysis [76] and cell signalling and epigenetic regulations [77,78]. It also controls gene expression, including nuclear factor kappa B (NF-κB), through histone binding mechanism, commonly known as biotinylation [79,80]. Therefore, this vitamin may also have anti-inflammatory effects [81,82]. Biotin is primarily synthesized from either malonyl CoA or pimeloyl-CoA [83,84]. Enzymes of the biotin biosynthesis pathway are overrepresented in enterotype 1, enriched in Bacteroides [10]. Bacteria that can produce vitamin B7 include Bacteroides fragilis, Prevotella copri, Fusobacterium varium, and Campylobacter coli [34]. In contrast, others are extensive vitamin B7 reducers, such as Lactobacillus murinus [85].

8. Vitamin B9/Folate

Folate, also known as vitamin B9, is a conjugate form of 4-aminobenzoic acid and L-glutamic acid. Vitamin B9 is supplied to the host primarily through diet and partially by gut microbiota [86]. Folate is an essential methyl donor nutrient that provides one-carbon units. It is also involved in synthesizing S-adenosylmethionine (SAM) required for cellular biosynthesis and DNA methylation [87]. This vitamin is vital for replicating and restoring nucleic acids, thus affecting cell survival rate and proliferation when deficient [88]. Additionally, folate is involved in regulating gene activities, regenerating the lining of the intestine, producing necessary chemicals for proper brain function, decreasing the growth of lymphocytes, and reducing natural killer cell cytotoxicity [89,90,91]. Thus, every living cell requires folate to perform a variety of these biochemical and biosynthetic processes. These cellular reactions are universal, but their metabolic pathways differ from organism to organism. Organisms such as fungi, plants, bacteria, and some specific archaea can undergo folate biosynthesis, and they use a similar pathway with slight modifications [92,93,94,95,96]. There are several bacteria that can produce folate in the gut, which include Bacteroides fragilis, Prevotella copri, Clostridium difficile, Lactobacillus Plantarum, L. reuteri, L. delbrueckii ssp. bulgaricus, Streptococcus thermophilus, Bifidobacterium spp. (some species), Fusobacterium varium, and Salmonella enterica [34,97]. Out of these bacteria, Bifidobacterium species are well studied. They are categorized on the basis of their folate-producing ability: high folate producers—Bifidobacterium bifidum and B. longum subsp. Infantis, and low folate producers—B. breve, B. longum subsp. longum, and B. adolescentis. Synthesis of folate requires one pterin moiety originating from 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPPP) and a para-aminobenzoic acid (pABA). The latter is an intermediate formed by cleaving pyruvate with 4-amino-4-deoxychorismate lyase enzyme [98]. Such enzymes are mostly confined to the genomes of Bifidobacterium species, including B. adolescentis and B. dentium Bd1 [99,100]; thus, they produce folate when DHPPP is available. Other common folate-producing bacteria are Lactobacilli. Unlike Bifidobacterium, several Lactobacillus species, including L. plantarum, L. sakei, L. delbrueckii, L. reuteri, L. helveticus, and L. fermentum can produce DHPPP; therefore, they synthesize folate when pABA is available [98]. Nevertheless, Lactococcus and Streptococcus possess a complete pathway for the de novo folate biosynthesis and do not require a supply of either DHPPP or pABA [101].
Due to its crucial role in methyl donor production, folate deficiency significantly impairs DNA replication. Folate depletion causes an increase in the intestinal mucosal crypt depth in the duodenum and jejunum [102], resulting in a reduced villus to crypt ratio [103]. In methyl donor-deficient mice induced by feeding a folate-deficient diet accompanied by an antibiotic, succinylsulfathiazole (1%), also had increased crypt depth and altered intestinal cell differentiation [87]. In rats, folate deficiency causes megaloblastic changes in the epithelial cell nuclei [102] and reduced crypt mitosis [103]. These changes were more remarkable in the ileum with crypt elongation, increased goblet cells, and decreased Paneth cells [87]. Thus, folate deficiency significantly alters intestinal cell morphology and is associated with increased occurrence of intestinal carcinogenesis [104,105]. Concomitant depletion of folate, riboflavin, vitamin B-6, and vitamin B-12 alter Wnt- signalling in the mouse colon and decrease apoptosis in the epithelium cell [106]. Unexpectedly, these changes are irreversible, even with the repletion of folate [103]. Although the gut bacteria can produce some folate, a folate-deficient diet significantly alters microbial diversity in the mice. It is shown that the abundances of Bacteroidales and Clostridiales decreased, and abundances of Lactobacillales and Erysipelotrichaceae taxa increased in folate-deficient mice [87].

9. Vitamin B12/Cobalamin

Vitamin B12, also known as cobalamin, is one of the largest and most complex vitamins [107]. The other forms of this vitamin include cyano-, methyl-, deoxyadenosyl-, and hydroxy-cobalamin. The cyano form is found as traces in diet, and it is used as a dietary supplement [108]. Like folate, cobalamin is involved in methyl donor synthesis, such as SAM. These methyl donors are crucial for nucleic acid synthesis and protein and lipid metabolism [109,110]. It is used as a cofactor for methionine synthase in sulphur amino acid metabolism to recycle homocysteine to methionine [111,112]. Cobalamin is also vital for the proper functioning of the central nervous system and the synthesis of red blood cells [110,111,113].
There are limited bacteria that can synthesize vitamin B12 in the human gut, and most of them use precorrin-2 as a precursor [34]. Approximately 20% of gut bacteria can produce vitamin B12, and more than 80% of gut bacteria require B12 for their metabolic reactions [114,115]. These include Pseudomonas denitrificans, Bacillus megaterium, and Propionibacterium freudenreichi, Bacteroides fragilis, Prevotella copri, Clostridium difficile, Faecalibacterium prausnitzii, Ruminococcus lactaris, Bifidobacterium animalis, B.infantis, B.longum, and Fusobacterium varium [34,48,116,117,118,119,120]. Notably, the first three bacteria are commercially used for vitamin B12 production [121]. Biosynthesis of B12 by microorganisms involves almost 30 genes and uses either aerobic or anaerobic pathways. The aerobic pathway has been studied in Pseudomonas denitrificans, and the anaerobic pathway has been studied in Salmonella typhimurium, Bacillus megaterium, and P. shermanii [122]. In general, Lactobacillus spp. were thought not to have a vitamin B12 biosynthetic pathway. However, the discovery of the conversion of glycerol into propanediol in lactic acid bacteria demonstrated their ability to produce vitamin B12 [121].
On the other hand, several other bacteria, including Bacteroides, do not have a vitamin B12 biosynthesis capability. However, most of them possess vitamin-B12-dependent enzymes [114]. The optimum functioning of these enzymes depends on dietary supply. The effects of vitamin B12 deficiency on colon morphology are similar to that of folate deficiency as they are closely associated with several cellular metabolic reactions. However, the impact of its deficiency on colon inflammation is not conclusive. Benight and colleagues reported that vitamin B12 deficiency protects against DSS-induced inflammations in C57BL/6 mice [123]. Contrarily, others demonstrated a reduction in cell differentiation and intestinal barrier in vitamin-B12-deficient rats [124]. Moreover, in patients with a vitamin B12 deficiency, the villus becomes shorter with a reduced villus/crypt ratio than in the control group [125]. Similarly, a dietary deficiency or surplus of vitamin B12 may likely influence the growth of gut microbiota. Unexpectedly, vitamin B12 deficiency did not alter gut microbial composition in healthy mice but altered it in DSS-induced colitis mice [126]. The short time (28 days) applied to induce the deficiency might be one of the reasons that gut microbial composition was not affected in the healthy mice. It was also likely that the animals that practice coprophagy could have maintained their vitamin status by eating feces [127]. However, the gut microbial profile in humans is influenced by the host vitamin B12 status. Vitamin B12 supplementation in humans increased the relative abundance of Prevotella, but decreased the abundance of Bacteroides [44]. Likewise, the relative abundance of Bacteroides has reduced with vitamin B12 supplementation in C57BL/6 mice [115]. Lurz and colleagues also showed that vitamin B12 supplementation in mice significantly decreased Parabacteroides and Lactobacillus and increased E. coli and Enterococcus abundances in a murine model of colitis [126]. Figure 1 summarizes the key intestinal bacteria that can produce B vitamins and their deficiency effects on gut health.

10. Factors Affecting Gut Microbial B-Vitamin Synthesis

The gut microbial vitamin B synthesis is affected by various factors, including antibiotics, free radicals, diet, and even an individual’s genetic make-up. The responses of exposure to antibiotics in B-vitamin synthesis are varied based on the type of antibiotics used. For instance, adding penicillin and aureomycin to the diet increased hepatic vitamin B2 concentration and excretion of B2 and B3 in the urine in male rats [128]. However, the administration of streptomycin [129] and cycloheximide [129] reduced vitamin B9 and B12 concentrations in the liver. The mixed responses of the vitamin synthesis upon antibiotic exposure are not well understood, but they might likely be caused by the selective alterations of the intestinal microbiota.
On the other hand, free radicals are chemical species that contain an unpaired electron and can induce oxidative stress [130]. One such example is nitric oxide, which forms complexes with metal ions, including cobalt [131], a structural component of vitamin B12, and thus makes it unavailable for bacterial vitamin B12 biosynthesis. Moreover, exposure of vitamin producers, such as B. fragilis, to free radicals such as hydrogen peroxide can suppress their growth [132], thereby reducing vitamin biosynthetic capacity.
Lastly, the host genetics, dietary habits, and lifestyle also shape the gut microbial profile [133,134]. Variants in human genes are associated with gut architecture and microbiome composition [133]. The presence of distinct vitamin B biosynthetic pathways in the human gut microbiota supports the notion that human genetic variation affects vitamin B synthesis [34]. Interestingly, Bonder and his colleagues identified a single nucleotide polymorphism that was associated with the abundance of Bifidobacterium genus [135], bacteria that produces several B vitamins. Moreover, a host diet acts as the substrates for those bacteria living in the gut and its impacts on gut microbial profile has been extensively studied [134,136,137]. Diets containing prebiotics and other dietary nutrients such as micronutrients and polyphenols can significantly influence the growth of beneficial bacteria [138,139], including vitamin producers. Some vitamins, such as riboflavin, act as a redox mediator and stimulate the growth of auxotrophic bacteria such as Faecaibacterium prauznitsii [135]. On the contrary, limiting those substrates will increase the competition between the microbes and microbes and the host in an environment where a symbiotic relationship is imminent [34].

11. Conclusions

B vitamins act as cofactors for several cellular metabolic reactions. These vitamins are usually supplied primarily through the dietary intake to meet the host’s daily requirements, including nourishing the intestinal ecology. Our gut microbiota can produce a certain amount of B vitamins. The biosynthesis of these vitamins in the gut is influenced by several factors, including exposure to antibiotics and free radicals, genetic make-up, dietary habits, and lifestyle. The bacterially synthesized vitamins are not enough to supply daily requirements for the host and gut microbiota. Competitions between the gut microbes and the host and microbes to microbes create the risk of vitamin shortage in the intestine if dietary supply is not optimum. Their status can affect the gut microbial composition, colonic health, and overall host metabolism. The gut microbiota of individuals are highly diverse; therefore, biosynthesis of B vitamins and their requirements are also different from person to person. The roles of microbially produced metabolites, including B vitamins, in intestinal health and regulating the host’s cell signalling continue to be discovered. Thus, opportunities exist to investigate how dietary B vitamins affect gut–host interactions.

Author Contributions

K.S.H. and S.A. contributed equally to this article regarding the literature search, review, and writing of original draft preparation; S.M. was responsible for the conceptualization, literature review, writing of the review, editing, and funding acquisition. All authors have read and agreed to the published version of the manuscript.


This research was funded by Memorial University of Newfoundland (Funding no. 20210719). KS Hossain and S Amarasena are supported by Memorial University Dean of Science Start-up Fund.

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the study design, data collection, interpretation, writing of the manuscript, or decision to publish the work.


  1. Kennedy, D.O. B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review. Nutrients 2016, 8, 68. [Google Scholar] [CrossRef][Green Version]
  2. Depeint, F.; Bruce, W.R.; Shangari, N.; Mehta, R.; O’Brien, P.J. Mitochondrial function and toxicity: Role of the B vitamin family on mitochondrial energy metabolism. Chem. Biol. Interact. 2006, 163, 94–112. [Google Scholar] [CrossRef]
  3. Rahman, S.; Baumgartner, M. B Vitamins: Small molecules, big effects. J. Inherit. Metab. Dis. 2019, 42, 579–580. [Google Scholar] [CrossRef][Green Version]
  4. Murphy, M.M.; Guéant, J.-L. B vitamins and one carbon metabolism micronutrients in health and disease. Biochimie 2020, 173, 1–2. [Google Scholar] [CrossRef]
  5. Peterson, C.T.; Rodionov, D.A.; Osterman, A.L.; Peterson, S.N. B Vitamins and Their Role in Immune Regulation and Cancer. Nutrients 2020, 12, 3380. [Google Scholar] [CrossRef]
  6. Martinez, D.L.; Tsuchiya, Y.; Gout, I. Coenzyme A biosynthetic machinery in mammalian cells. Biochem. Soc. Trans. 2014, 42, 1112–1117. [Google Scholar] [CrossRef]
  7. Spinneker, A.; Sola, R.; Lemmen, V.; Castillo, M.J.; Pietrzik, K.; González-Gross, M. Vitamin B6 status, deficiency and its consequences--an overview. Nutr. Hosp. 2007, 22, 7–24. [Google Scholar]
  8. Thursby, E.; Juge, N. Introduction to the human gut microbiota. Biochem. J. 2017, 474, 1823–1836. [Google Scholar] [CrossRef]
  9. Marchesi, J.R. Prokaryotic and Eukaryotic Diversity of the Human Gut. Adv. Appl. Microbiol. 2010, 72, 43–62. [Google Scholar] [CrossRef]
  10. Arumugam, M.; Raes, J.; Pelletier, E.; Le Paslier, D.; Yamada, T.; Mende, D.R.; Fernandes, G.R.; Tap, J.; Bruls, T.; Batto, J.M.; et al. Enterotypes of the human gut microbiome. Nature 2011, 473, 174–180. [Google Scholar] [CrossRef]
  11. Bäumler, A.J.; Sperandio, V. Interactions between the microbiota and pathogenic bacteria in the gut. Nature 2016, 535, 85–93. [Google Scholar] [CrossRef][Green Version]
  12. Den Besten, G.; van Eunen, K.; Groen, A.K.; Venema, K.; Reijngoud, D.-J.; Bakker, B.M. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J. Lipid Res. 2013, 54, 2325–2340. [Google Scholar] [CrossRef][Green Version]
  13. Gensollen, T.; Iyer, S.S.; Kasper, D.L.; Blumberg, R.S. How colonization by microbiota in early life shapes the immune system. Science 2016, 352, 539–544. [Google Scholar] [CrossRef] [PubMed][Green Version]
  14. Dogra, S.K.; Doré, J.; Damak, S. Gut Microbiota Resilience: Definition, Link to Health and Strategies for Intervention. Front. Microbiol. 2020, 11, 572921. [Google Scholar] [CrossRef] [PubMed]
  15. O’Toole, P.W.; Claesson, M. Gut microbiota: Changes throughout the lifespan from infancy to elderly. Int. Dairy J. 2010, 20, 281–291. [Google Scholar] [CrossRef]
  16. Biasucci, G.; Benenati, B.; Morelli, L.; Bessi, E.; Boehm, G. Cesarean Delivery May Affect the Early Biodiversity of Intestinal Bacteria. J. Nutr. 2008, 138, 1796S–1800S. [Google Scholar] [CrossRef][Green Version]
  17. Neu, J.; Rushing, J. Cesarean Versus Vaginal Delivery: Long-term Infant Outcomes and the Hygiene Hypothesis. Clin. Perinatol. 2011, 38, 321–331. [Google Scholar] [CrossRef][Green Version]
  18. Odamaki, T.; Kato, K.; Sugahara, H.; Hashikura, N.; Takahashi, S.; Xiao, J.-Z.; Abe, F.; Osawa, R. Age-Related changes in gut microbiota composition from newborn to centenarian: A cross-sectional study. BMC Microbiol. 2016, 16, 90. [Google Scholar] [CrossRef] [PubMed][Green Version]
  19. Rogers, M.A.M.; Aronoff, D.M. The influence of non-steroidal anti-inflammatory drugs on the gut microbiome. Clin. Microbiol. Infect. 2016, 22, 178.e1–178.e9. [Google Scholar] [CrossRef][Green Version]
  20. Jernberg, C.; Löfmark, S.; Edlund, C.; Jansson, J.K. Long-Term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology 2010, 156, 3216–3223. [Google Scholar] [CrossRef][Green Version]
  21. Heiman, M.L.; Greenway, F.L. A healthy gastrointestinal microbiome is dependent on dietary diversity. Mol. Metab. 2016, 5, 317–320. [Google Scholar] [CrossRef] [PubMed]
  22. Uebanso, T.; Shimohata, T.; Mawatari, K.; Takahashi, A. Functional Roles of B-Vitamins in the Gut and Gut Microbiome. Mol. Nutr. Food Res. 2020, 64, 2000426. [Google Scholar] [CrossRef]
  23. Manzetti, S.; Zhang, J.; van der Spoel, D. Thiamin function, metabolism, uptake, and transport. Biochemistry 2014, 53, 821–835. [Google Scholar] [CrossRef]
  24. Sriram, K.; Manzanares, W.; Joseph, K. Thiamine in Nutrition Therapy. Nutr. Clin. Pract. 2012, 27, 41–50. [Google Scholar] [CrossRef]
  25. Said, H.M. Recent advances in transport of water-soluble vitamins in organs of the digestive system: A focus on the colon and the pancreas. Am. J. Physiol. Liver Physiol. 2013, 305, G601–G610. [Google Scholar] [CrossRef] [PubMed][Green Version]
  26. Costliow, Z.A.; Degnan, P.H. Thiamine Acquisition Strategies Impact Metabolism and Competition in the Gut Microbe Bacteroides thetaiotaomicron. mSystems 2017, 2, e00116-17. [Google Scholar] [CrossRef][Green Version]
  27. Said, H.M.; Ortiz, A.; Subramanian, V.S.; Neufeld, E.J.; Moyer, M.P.; Dudeja, P.K. Mechanism of thiamine uptake by human colonocytes: Studies with cultured colonic epithelial cell line NCM460. Am. J. Physiol. Gastrointest. Liver Physiol. 2001, 281, G144–G150. [Google Scholar] [CrossRef] [PubMed]
  28. Nabokina, S.M.; Inoue, K.; Subramanian, V.S.; Valle, J.E.; Yuasa, H.; Said, H.M. Molecular Identification and Functional Characterization of the Human Colonic Thiamine Pyrophosphate Transporter. J. Biol. Chem. 2014, 289, 4405–4416. [Google Scholar] [CrossRef] [PubMed][Green Version]
  29. Mathis, D.; Shoelson, S.E. Immunometabolism: An emerging frontier. Nat. Rev. Immunol. 2011, 11, 81–83. [Google Scholar] [CrossRef][Green Version]
  30. Kunisawa, J.; Sugiura, Y.; Wake, T.; Nagatake, T.; Suzuki, H.; Nagasawa, R.; Shikata, S.; Honda, K.; Hashimoto, E.; Suzuki, Y.; et al. Mode of Bioenergetic Metabolism during B Cell Differentiation in the Intestine Determines the Distinct Requirement for Vitamin B 1. Cell Rep. 2015, 13, 122–131. [Google Scholar] [CrossRef][Green Version]
  31. Pinto, J.T.; Zempleni, J. Riboflavin. Adv. Nutr. 2016, 7, 973–975. [Google Scholar] [CrossRef][Green Version]
  32. Sundaram, U. Regulation of intestinal vitamin B(2) absorption. Focus on “Riboflavin uptake by human-derived colonic epithelial NCM460 cells”. Am. J. Physiol. Cell Physiol. 2000, 278, C268–C269. [Google Scholar] [CrossRef] [PubMed][Green Version]
  33. Steinert, R.E.; Sadaghian Sadabad, M.; Harmsen, H.J.; Weber, P. The prebiotic concept and human health: A changing landscape with riboflavin as a novel prebiotic candidate? Eur. J. Clin. Nutr. 2016, 70, 1348–1353. [Google Scholar] [CrossRef] [PubMed]
  34. Magnusdottir, S.; Ravcheev, D.; De Crécy-Lagard, V.; Thiele, I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front. Genet. 2015, 6, 148. [Google Scholar] [CrossRef][Green Version]
  35. Thakur, K.; Tomar, S.K.; De, S. Lactic acid bacteria as a cell factory for riboflavin production. Microb. Biotechnol. 2016, 9, 441–451. [Google Scholar] [CrossRef]
  36. García-Angulo, V.A. Overlapping riboflavin supply pathways in bacteria. Crit. Rev. Microbiol. 2017, 43, 196–209. [Google Scholar] [CrossRef]
  37. Yates, C.; Evans, G.; Pearson, T.; Powers, H. Absence of luminal riboflavin disturbs early postnatal development of the gastrointestinal tract. Dig. Dis. Sci. 2003, 48, 1159–1164. [Google Scholar] [CrossRef]
  38. Yates, C.A.; Evans, G.S.; Powers, H.J. Riboflavin deficiency: Early effects on post-weaning development of the duodenum in rats. Br. J. Nutr. 2001, 86, 593–599. [Google Scholar] [CrossRef][Green Version]
  39. Lee, E.-S.; Corfe, B.M.; Powers, H.J. Riboflavin depletion of intestinal cells in vitro leads to impaired energy generation and enhanced oxidative stress. Eur. J. Nutr. 2013, 52, 1513–1521. [Google Scholar] [CrossRef] [PubMed]
  40. Williams, E.A.; Rumsey, R.D.; Powers, H.J. An investigation into the reversibility of the morphological and cytokinetic changes seen in the small intestine of riboflavin deficient rats. Gut 1996, 39, 220–225. [Google Scholar] [CrossRef][Green Version]
  41. Williams, E.A.; Rumsey, R.D.; Powers, H.J. Cytokinetic and structural responses of the rat small intestine to riboflavin depletion. Br. J. Nutr. 1996, 75, 315–324. [Google Scholar] [CrossRef] [PubMed][Green Version]
  42. Williams, E.A.; Powers, H.J.; Rumsey, R.D.E. Morphological changes in the rat small intestine in response to riboflavin depletion. Br. J. Nutr. 1995, 73, 141–146. [Google Scholar] [CrossRef] [PubMed][Green Version]
  43. Nakano, E.; Mushtaq, S.; Heath, P.R.; Lee, E.-S.; Bury, J.P.; Riley, S.A.; Powers, H.J.; Corfe, B.M. Riboflavin Depletion Impairs Cell Proliferation in Adult Human Duodenum: Identification of Potential Effectors. Am. J. Dig. Dis. 2010, 56, 1007–1019. [Google Scholar] [CrossRef] [PubMed]
  44. Carrothers, J.M.; York, M.A.; Brooker, S.L.; Lackey, K.A.; Williams, J.E.; Shafii, B.; Price, W.J.; Settles, M.L.; McGuire, M.A.; McGuire, M.K. Fecal Microbial Community Structure Is Stable over Time and Related to Variation in Macronutrient and Micronutrient Intakes in Lactating Women. J. Nutr. 2015, 145, 2379–2388. [Google Scholar] [CrossRef][Green Version]
  45. Qi, Y.; Lohman, J.; Bratlie, K.M.; Peroutka-Bigus, N.; Bellaire, B.; Wannemuehler, M.; Yoon, K.; Barrett, T.A.; Wang, Q. Vitamin C and B 3 as new biomaterials to alter intestinal stem cells. J. Biomed. Mater. Res. Part A 2019, 107, 1886–1897. [Google Scholar] [CrossRef]
  46. Gazzaniga, F.; Stebbins, R.; Chang, S.Z.; McPeek, M.A.; Brenner, C. Microbial NAD Metabolism: Lessons from Comparative Genomics. Microbiol. Mol. Biol. Rev. 2009, 73, 529–541. [Google Scholar] [CrossRef][Green Version]
  47. Kurnasov, O.; Goral, V.; Colabroy, K.; Gerdes, S.; Anantha, S.; Osterman, A.; Begley, T.P. NAD Biosynthesis: Identification of the Tryptophan to Quinolinate Pathway in Bacteria. Chem. Biol. 2003, 10, 1195–1204. [Google Scholar] [CrossRef] [PubMed][Green Version]
  48. Deguchi, Y.; Morishita, T.; Mutai, M. Comparative Studies on Synthesis of Water-soluble Vitamins among Human Species of Bifidobacteria. Agric. Biol. Chem. 1985, 49, 13–19. [Google Scholar]
  49. Rossolillo, P.; Marinoni, I.; Galli, E.; Colosimo, A.; Albertini, A.M. YrxA Is the Transcriptional Regulator That Represses De Novo NAD Biosynthesis in Bacillus subtilis. J. Bacteriol. 2005, 187, 7155–7160. [Google Scholar] [CrossRef][Green Version]
  50. Rodionov, D.A.; Li, X.; Rodionova, I.A.; Yang, C.; Sorci, L.; Dervyn, E.; Martynowski, D.; Zhang, H.; Gelfand, M.; Osterman, A.L. Transcriptional regulation of NAD metabolism in bacteria: Genomic reconstruction of NiaR (YrxA) regulon. Nucleic Acids Res. 2008, 36, 2032–2046. [Google Scholar] [CrossRef] [PubMed]
  51. Kumar, J.S.; Subramanian, V.S.; Kapadia, R.; Kashyap, M.L.; Said, H.M. Mammalian colonocytes possess a carrier-mediated mechanism for uptake of vitamin B3 (niacin): Studies utilizing human and mouse colonic preparations. Am. J. Physiol. Gastrointest. Liver Physiol. 2013, 305, G207–G213. [Google Scholar] [CrossRef] [PubMed][Green Version]
  52. Fangmann, D.; Theismann, E.-M.; Türk, K.; Schulte, D.M.; Relling, I.; Hartmann, K.; Keppler, J.K.; Knipp, J.-R.; Rehman, A.; Heinsen, F.-A.; et al. Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans. Diabetes Care 2017, 41, 398–405. [Google Scholar] [CrossRef] [PubMed][Green Version]
  53. Li, J.; Kong, D.; Wang, Q.; Wu, W.; Tang, Y.; Bai, T.; Guo, L.; Wei, L.; Zhang, Q.; Yu, Y.; et al. Niacin ameliorates ulcerative colitis via prostaglandin D 2 -mediated D prostanoid receptor 1 activation. EMBO Mol. Med. 2017, 9, 571–588. [Google Scholar] [CrossRef]
  54. Santoru, M.L.; Piras, C.; Murgia, F.; Spada, M.; Tronci, L.; Leoni, V.P.; Serreli, G.; Deiana, M.; Atzori, L. Modulatory Effect of Nicotinic Acid on the Metabolism of Caco-2 Cells Exposed to IL-1β and LPS. Metabolites 2020, 10, 204. [Google Scholar] [CrossRef]
  55. Filippi, J.; Al-Jaouni, R.; Wiroth, J.B.; Hébuterne, X.; Schneider, S.M. Nutritional deficiencies in patients with Crohn’s disease in remission. Inflamm. Bowel Dis. 2006, 12, 185–191. [Google Scholar] [CrossRef] [PubMed]
  56. Ragaller, V.; Lebzien, P.; Südekum, K.H.; Hüther, L.; Flachowsky, G. Pantothenic acid in ruminant nutrition: A review. J. Anim. Physiol. Anim. Nutr. 2011, 95, 6–16. [Google Scholar] [CrossRef]
  57. Hayflick, S.J. Defective pantothenate metabolism and neurodegeneration. Biochem. Soc. Trans. 2014, 42, 1063–1068. [Google Scholar] [CrossRef][Green Version]
  58. Leonardi, R.; Jackowski, S. Biosynthesis of Pantothenic Acid and Coenzyme A. EcoSal Plus 2007, 2, 2. [Google Scholar] [CrossRef][Green Version]
  59. Begley, T.P.; Kinsland, C.; Strauss, E. The biosynthesis of coenzyme a in bacteria. Vitam. Horm. 2001, 61, 157–171. [Google Scholar] [CrossRef]
  60. Tahiliani, A.G.; Beinlich, C.J. Pantothenic Acid in Health and Disease. Vitam. Horm. 1991, 46, 165–228. [Google Scholar] [CrossRef]
  61. Frederick, C.; Neidhardt, J.L.I.; Magasanik, K.B.; Brooks, L.; Moselio, S.; Edwin, U.H. Escherichia coli and Salmonella typhimurium. Cell. Mol. Biol. 1988, 63, 463–464. [Google Scholar]
  62. Epelbaum, S.; LaRossa, R.A.; VanDyk, T.K.; Elkayam, T.; Chipman, D.M.; Barak, Z. Branched-Chain amino acid biosynthesis in Salmonella typhimurium: A quantitative analysis. J. Bacteriol. 1998, 180, 4056–4067. [Google Scholar] [CrossRef][Green Version]
  63. Yao, C.; Chou, J.; Wang, T.; Zhao, H.; Zhang, B. Pantothenic Acid, Vitamin C, and Biotin Play Important Roles in the Growth of Lactobacillus helveticus. Front. Microbiol. 2018, 9, 1194. [Google Scholar] [CrossRef][Green Version]
  64. Parra, M.; Stahl, S.; Hellmann, H. Vitamin B6 and Its Role in Cell Metabolism and Physiology. Cells 2018, 7, 84. [Google Scholar] [CrossRef][Green Version]
  65. Mooney, S.; Leuendorf, J.-E.; Hendrickson, C.; Hellmann, H. Vitamin B6: A Long Known Compound of Surprising Complexity. Molecules 2009, 14, 329–351. [Google Scholar] [CrossRef] [PubMed][Green Version]
  66. Choudhury, S.R.; Singh, S.K.; Roy, S.; Sengupta, D.N. An insight into the sequential, structural and phylogenetic properties of banana 1-aminocyclopropane-1-carboxylate synthase 1 and study of its interaction with pyridoxal-5’-phosphate and aminoethoxyvinylglycine. J. Biosci. 2010, 35, 281–294. [Google Scholar] [CrossRef]
  67. Plecko, B.; Stöckler, S. Vitamin B6 dependent seizures. Can. J. Neurol. Sci. 2009, 36, S73–S77. [Google Scholar] [PubMed]
  68. Geng, M.-Y.; Saito, H.; Katsuki, H. Effects of vitamin B6 and its related compounds on survival of cultured brain neurons. Neurosci. Res. 1995, 24, 61–65. [Google Scholar] [CrossRef]
  69. Yoshii, K.; Hosomi, K.; Sawane, K.; Kunisawa, J. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front. Nutr. 2019, 6, 48. [Google Scholar] [CrossRef] [PubMed][Green Version]
  70. Mayengbam, S.; Chleilat, F.; Reimer, R.A. Dietary Vitamin B6 Deficiency Impairs Gut Microbiota and Host and Microbial Metabolites in Rats. Biomedicines 2020, 8, 469. [Google Scholar] [CrossRef] [PubMed]
  71. Vitellio, P.; Celano, G.; Bonfrate, L.; Gobbetti, M.; Portincasa, P.; De Angelis, M. Effects of Bifidobacterium longum and Lactobacillus rhamnosus on Gut Microbiota in Patients with Lactose Intolerance and Persisting Functional Gastrointestinal Symptoms: A Randomised, Double-Blind, Cross-Over Study. Nutrients 2019, 11, 886. [Google Scholar] [CrossRef] [PubMed][Green Version]
  72. Ligaarden, S.C.; Farup, P. Low intake of vitamin B6 is associated with irritable bowel syndrome symptoms. Nutr. Res. 2011, 31, 356–361. [Google Scholar] [CrossRef]
  73. Yin, L.; Li, J.; Wang, H.; Yi, Z.; Wang, L.; Zhang, S.; Li, X.; Wang, Q.; Li, J.; Yang, H.; et al. Effects of vitamin B6 on the growth performance, intestinal morphology, and gene expression in weaned piglets that are fed a low-protein diet1. J. Anim. Sci. 2020, 98, skaa022. [Google Scholar] [CrossRef]
  74. Javanmardi, S.; Tavabe, K.R.; Rosentrater, K.A.; Solgi, M.; Bahadori, R. Effects of different levels of vitamin B6 in tank water on the Nile tilapia (Oreochromis niloticus): Growth performance, blood biochemical parameters, intestine and liver histology, and intestinal enzyme activity. Fish Physiol. Biochem. 2020, 46, 1909–1920. [Google Scholar] [CrossRef]
  75. Matyaszczyk, M.; Karczmarewicz, E.; Czarnowska, E.; Reynolds, R.D.; Lorenc, R.S. Vitamin B-6 deficiency alters rat enterocyte calcium homeostasis but not duodenal transport. J. Nutr. 1993, 123, 204–215. [Google Scholar] [PubMed]
  76. Tadi, K.G.B.P. Biotin; StatPearls: Tampa, FL, USA, 2021. [Google Scholar]
  77. Zempleni, J.; Wijeratne, S.S.; Hassan, Y.I. Biotin. Biofactors 2009, 35, 36–46. [Google Scholar] [CrossRef][Green Version]
  78. Zempleni, J. Uptake, Localization, and Noncarboxylase Roles of Biotin. Annu. Rev. Nutr. 2005, 25, 175–196. [Google Scholar] [CrossRef]
  79. Kothapalli, N.; Camporeale, G.; Kueh, A.; Chew, Y.C.; Oommen, A.M.; Griffin, J.B.; Zempleni, J. Biological functions of biotinylated histones. J. Nutr. Biochem. 2005, 16, 446–448. [Google Scholar] [CrossRef][Green Version]
  80. Liu, T.; Zhang, L.; Joo, D.; Sun, S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther. 2017, 2, 17023. [Google Scholar] [CrossRef][Green Version]
  81. Agrawal, S.; Agrawal, A.; Said, H.M. Biotin deficiency enhances the inflammatory response of human dendritic cells. Am. J. Physiol. Physiol. 2016, 311, C386–C391. [Google Scholar] [CrossRef] [PubMed]
  82. Elahi, A.; Sabui, S.; Narasappa, N.N.; Agrawal, S.; Lambrecht, N.W.; Agrawal, A.; Said, H.M. Biotin Deficiency Induces Th1- and Th17-Mediated Proinflammatory Responses in Human CD4+ T Lymphocytes via Activation of the mTOR Signaling Pathway. J. Immunol. 2018, 200, 2563–2570. [Google Scholar] [CrossRef][Green Version]
  83. Bi, H.; Zhu, L.; Jia, J.; Cronan, J.E. A Biotin Biosynthesis Gene Restricted to Helicobacter. Sci. Rep. 2016, 6, 21162. [Google Scholar] [CrossRef][Green Version]
  84. Entcheva, P.; Phillips, D.A.; Streit, W.R. Functional Analysis of Sinorhizobium meliloti Genes Involved in Biotin Synthesis and Transport. Appl. Environ. Microbiol. 2002, 68, 2843–2848. [Google Scholar] [CrossRef][Green Version]
  85. Hayashi, A.; Mikami, Y.; Miyamoto, K.; Kamada, N.; Sato, T.; Mizuno, S.; Naganuma, M.; Teratani, T.; Aoki, R.; Fukuda, S.; et al. Intestinal Dysbiosis and Biotin Deprivation Induce Alopecia through Overgrowth of Lactobacillus murinus in Mice. Cell Rep. 2017, 20, 1513–1524. [Google Scholar] [CrossRef]
  86. Iyer, R.; Tomar, S. Folate: A Functional Food Constituent. J. Food Sci. 2009, 74, R114–R122. [Google Scholar] [CrossRef]
  87. Da Silva, A.V.A.; Oliveira, S.B.D.C.; Di Rienzi, S.C.; Brown-Steinke, K.; Dehan, L.M.; Rood, J.K.; Carreira, V.S.; Le, H.; Maier, E.A.; Betz, K.J.; et al. Murine Methyl Donor Deficiency Impairs Early Growth in Association with Dysmorphic Small Intestinal Crypts and Reduced Gut Microbial Community Diversity. Curr. Dev. Nutr. 2019, 3, nzy070. [Google Scholar] [CrossRef]
  88. Stover, P.J. Physiology of folate and vitamin B12 in health and disease. Nutr. Rev. 2004, 62, S3–S12, discussion S13. [Google Scholar] [CrossRef]
  89. Gazzali, A.M.; Lobry, M.; Colombeau, L.; Acherar, S.; Azaïs, H.; Mordon, S.; Arnoux, P.; Baros, F.; Vanderesse, R.; Frochot, C. Stability of folic acid under several parameters. Eur. J. Pharm. Sci. 2016, 93, 419–430. [Google Scholar] [CrossRef]
  90. Courtemanche, C.; Elson-Schwab, I.; Mashiyama, S.T.; Kerry, N.; Ames, B.N. Folate Deficiency Inhibits the Proliferation of Primary Human CD8+T Lymphocytes In Vitro. J. Immunol. 2004, 173, 3186–3192. [Google Scholar] [CrossRef][Green Version]
  91. Troen, A.M.; Mitchell, B.; Sorensen, B.; Wener, M.H.; Johnston, A.; Wood, B.; Selhub, J.; McTiernan, A.; Yasui, Y.; Oral, E.; et al. Unmetabolized Folic Acid in Plasma Is Associated with Reduced Natural Killer Cell Cytotoxicity among Postmenopausal Women. J. Nutr. 2006, 136, 189–194. [Google Scholar] [CrossRef]
  92. Bermingham, A.; Derrick, J.-P. The folic acid biosynthesis pathway in bacteria: Evaluation of potential for antibacterial drug discovery. BioEssays 2002, 24, 637–648. [Google Scholar] [CrossRef]
  93. Hanson, A.D.; Gregory, J.F., III. Synthesis and turnover of folates in plants. Curr. Opin. Plant Biol. 2002, 5, 244–249. [Google Scholar] [CrossRef]
  94. White, R.H. Analysis and characterization of the folates in the nonmethanogenic archaebacteria. J. Bacteriol. 1988, 170, 4608–4612. [Google Scholar] [CrossRef][Green Version]
  95. Levin, I.; Giladi, M.; Altman-Price, N.; Ortenberg, R.; Mevarech, M. An alternative pathway for reduced folate biosynthesis in bacteria and halophilic archaea. Mol. Microbiol. 2004, 54, 1307–1318. [Google Scholar] [CrossRef] [PubMed]
  96. de Crécy-Lagard, V.; El Yacoubi, B.; de la Garza, R.D.; Noiriel, A.; Hanson, A.D. Comparative genomics of bacterial and plant folate synthesis and salvage: Predictions and validations. BMC Genom. 2007, 8, 245. [Google Scholar] [CrossRef][Green Version]
  97. Crittenden, R.G.; Martinez, N.R.; Playne, M.J. Synthesis and utilisation of folate by yoghurt starter cultures and probiotic bacteria. Int. J. Food Microbiol. 2003, 80, 217–222. [Google Scholar] [CrossRef]
  98. Rossi, M.; Amaretti, A.; Raimondi, S. Folate Production by Probiotic Bacteria. Nutrients 2011, 3, 118–134. [Google Scholar] [CrossRef][Green Version]
  99. Ventura, M.; Canchaya, C.; Tauch, A.; Chandra, G.; Fitzgerald, G.F.; Chater, K.F.; van Sinderen, D. Genomics of Actinobacteria: Tracing the Evolutionary History of an Ancient Phylum. Microbiol. Mol. Biol. Rev. 2007, 71, 495–548. [Google Scholar] [CrossRef] [PubMed][Green Version]
  100. Ventura, M.; Turroni, F.; Zomer, A.; Foroni, E.; Giubellini, V.; Bottacini, F.; Canchaya, C.; Claesson, M.; He, F.; Mantzourani, M.; et al. The Bifidobacterium dentium Bd1 Genome Sequence Reflects Its Genetic Adaptation to the Human Oral Cavity. PLoS Genet. 2009, 5, e1000785. [Google Scholar] [CrossRef]
  101. Makarova, K.S.; Koonin, E.V. Evolutionary Genomics of Lactic Acid Bacteria. J. Bacteriol. 2007, 189, 1199–1208. [Google Scholar] [CrossRef][Green Version]
  102. Klipstein, F.A.; Lipton, S.D.; Schenk, E.A. Folate deficiency of the intestinal mucosa. Am. J. Clin. Nutr. 1973, 26, 728–737. [Google Scholar] [CrossRef] [PubMed]
  103. Howard, L.; Wagner, C.; Schenker, S. Malabsorption of Thiamin in Folate-deficient Rats. J. Nutr. 1974, 104, 1024–1032. [Google Scholar] [CrossRef][Green Version]
  104. Kim, Y.; Shirwadkar, S.; Choi, S.; Puchyr, M.; Wang, Y.; Mason, J.B. Effects of dietary folate on DNA strand breaks within mutation-prone exons of the p53 gene in rat colon. Gastroenterology 2000, 119, 151–161. [Google Scholar] [CrossRef] [PubMed]
  105. Pufulete, M.; Al-Ghnaniem, R.; Leather, A.J.; Appleby, P.; Gout, S.; Terry, C.; Emery, P.W.; Sanders, T.A. Folate status, genomic DNA hypomethylation, and risk of colorectal adenoma and cancer: A case control study. Gastroenterology 2003, 124, 1240–1248. [Google Scholar] [CrossRef]
  106. Liu, Z.; Choi, S.-W.; Crott, J.W.; Keyes, M.K.; Jang, H.; Smith, D.E.; Kim, M.; Laird, P.W.; Bronson, R.; Mason, J.B. Mild Depletion of Dietary Folate Combined with Other B Vitamins Alters Multiple Components of the Wnt Pathway in Mouse Colon. J. Nutr. 2007, 137, 2701–2708. [Google Scholar] [CrossRef] [PubMed]
  107. Watanabe, F. Vitamin B12 Sources and Bioavailability. Exp. Biol. Med. 2007, 232, 1266–1274. [Google Scholar] [CrossRef]
  108. Scott, J.M. Bioavailability of vitamin B12. Eur. J. Clin. Nutr. 1997, 51 (Suppl. 1), S49–S53. [Google Scholar]
  109. Coates, P.M. Encyclopedia of Dietary Supplements; Dietary Supplements; Marcel Dekker: New York, NY, USA, 2005. [Google Scholar]
  110. Marriott, B.P.; Birt, D.F.; Stalling, V.A.; Yates, A.A. Present Knowledge in Nutrition, 11th ed.; Academic Press: Cambridge, MA, USA, 2020; p. 678. [Google Scholar]
  111. Thiamin, R. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline; National Academy Press: Washington, DC, USA, 1998. [Google Scholar]
  112. Ross, A.C.; Caballero, B.; Cousins, R.J.; Tucker, K.L. (Eds.) Modern Nutrition in Health and Disease, 11th ed.; Wolters Kluwer Health/Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2014. [Google Scholar]
  113. Allen, L.H. Vitamin B-12. Adv. Nutr. 2012, 3, 54–55. [Google Scholar] [CrossRef]
  114. Degnan, P.H.; Barry, N.A.; Mok, K.C.; Taga, M.E.; Goodman, A.L. Human Gut Microbes Use Multiple Transporters to Distinguish Vitamin B12 Analogs and Compete in the Gut. Cell Host Microbe 2014, 15, 47–57. [Google Scholar] [CrossRef] [PubMed][Green Version]
  115. Kelly, C.J.; Alexeev, E.E.; Farb, L.; Vickery, T.W.; Zheng, L.; Eric, L.C.; Kitzenberg, D.A.; Battista, K.D.; Kominsky, D.J.; Robertson, C.E.; et al. Oral vitamin B12 supplement is delivered to the distal gut, altering the corrinoid profile and selectively depleting Bacteroides in C57BL/6 mice. Gut Microbes 2019, 10, 654–662. [Google Scholar] [CrossRef]
  116. Masuda, M.; Ide, M.; Utsumi, H.; Niiro, T.; Shimamura, Y.; Murata, M. Production Potency of Folate, Vitamin B12, and Thiamine by Lactic Acid Bacteria Isolated from Japanese Pickles. Biosci. Biotechnol. Biochem. 2012, 76, 2061–2067. [Google Scholar] [CrossRef][Green Version]
  117. Gu, Q.; Zhang, C.; Song, D.; Li, P.; Zhu, X. Enhancing vitamin B12 content in soy-yogurt by Lactobacillus reuteri. Int. J. Food Microbiol. 2015, 206, 56–59. [Google Scholar] [CrossRef]
  118. Piwowarek, K.; Lipińska, E.; Hać-Szymańczuk, E.; Kieliszek, M.; Ścibisz, I. Propionibacterium spp.—source of propionic acid, vitamin B12, and other metabolites important for the industry. Appl. Microbiol. Biotechnol. 2018, 102, 515–538. [Google Scholar] [CrossRef][Green Version]
  119. Lee, J.-H.; O’Sullivan, J.D. Genomic Insights into Bifidobacteria. Microbiol. Mol. Biol. Rev. 2010, 74, 378–416. [Google Scholar] [CrossRef][Green Version]
  120. Song, H.; Yoo, Y.; Hwang, J.; Na, Y.-C.; Kim, H.S. Faecalibacterium prausnitzii subspecies–level dysbiosis in the human gut microbiome underlying atopic dermatitis. J. Allergy Clin. Immunol. 2015, 137, 852–860. [Google Scholar] [CrossRef][Green Version]
  121. Kleerebezem, M.; Hugenholtz, J. Metabolic pathway engineering in lactic acid bacteria. Curr. Opin. Biotechnol. 2003, 14, 232–237. [Google Scholar] [CrossRef]
  122. Moore, S.; Warren, M.J. The anaerobic biosynthesis of vitamin B12. Biochem. Soc. Trans. 2012, 40, 581–586. [Google Scholar] [CrossRef]
  123. Benight, N.M.; Stoll, B.; Chacko, S.; da Silva, V.R.; Marini, J.C.; Gregory, J.F.; Stabler, S.P.; Burrin, D.G. B-Vitamin deficiency is protective against DSS-induced colitis in mice. Am. J. Physiol. Liver Physiol. 2011, 301, G249–G259. [Google Scholar] [CrossRef][Green Version]
  124. Bressenot, A.; Pooya, S.; Bossenmeyer-Pourie, C.; Gauchotte, G.; Germain, A.; Chevaux, J.-B.; Coste, F.; Vignaud, J.-M.; Guéant, J.-L.; Peyrin-Biroulet, L. Methyl donor deficiency affects small-intestinal differentiation and barrier function in rats. Br. J. Nutr. 2013, 109, 667–677. [Google Scholar] [CrossRef][Green Version]
  125. Berg, N.O.; Dahlqvist, A.; Lindberg, T.; Lindstrand, K.; Nordén, Å. Morphology, Dipeptidases and Disaccharidases of Small Intestinal Mucosa in Vitamin B12 and Folic Acid Deficiency. Scand. J. Haematol. 2009, 9, 167–173. [Google Scholar] [CrossRef]
  126. Lurz, E.; Horne, R.G.; Määttänen, P.; Wu, R.Y.; Botts, S.R.; Li, B.; Rossi, L.; Johnson-Henry, K.C.; Pierro, A.; Surette, M.G.; et al. Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis. Front. Nutr. 2020, 7, 83. [Google Scholar] [CrossRef] [PubMed]
  127. Degnan, P.H.; Taga, M.E.; Goodman, A.L. Vitamin B 12 as a Modulator of Gut Microbial Ecology. Cell Metab. 2014, 20, 769–778. [Google Scholar] [CrossRef][Green Version]
  128. Guggenheim, K.; Halevy, S.; Hartmann, I.; Zamir, R. The Effect of Antibiotics on the Metabolism of Certain B Vitamins. J. Nutr. 1953, 50, 245–253. [Google Scholar] [CrossRef]
  129. Tan, C.H.; Blaisdell, S.J.; Hansen, H.J. Mouse transcobalamin II metabolism: The effects of antibiotics on the clearance of vitamin B12 from the serum transcobalamin II-vitamin B12 complex and the reappearance of the free serum transcobalamin II in the mouse. Biochim. Biophys. Acta (BBA)-Gen. Subj. 1973, 320, 469–477. [Google Scholar] [CrossRef]
  130. Di Meo, S.; Venditti, P. Evolution of the Knowledge of Free Radicals and Other Oxidants. Oxidative Med. Cell. Longev. 2020, 2020, 9829176. [Google Scholar] [CrossRef]
  131. Haurani, F.I. The Effects of Free Radicals on Cobalamin and Iron. Free Radic. Res. Commun. 1989, 7, 241–243. [Google Scholar] [CrossRef]
  132. Rocha, E.R.; Selby, T.; Coleman, J.P.; Smith, C.J. Oxidative stress response in an anaerobe, Bacteroides fragilis: A role for catalase in protection against hydrogen peroxide. J. Bacteriol. 1996, 178, 6895–6903. [Google Scholar] [CrossRef] [PubMed][Green Version]
  133. Hall, A.B.; Tolonen, A.; Xavier, R.J. Human genetic variation and the gut microbiome in disease. Nat. Rev. Genet. 2017, 18, 690–699. [Google Scholar] [CrossRef]
  134. Flint, H.J.; Duncan, S.; Louis, P. The impact of nutrition on intestinal bacterial communities. Curr. Opin. Microbiol. 2017, 38, 59–65. [Google Scholar] [CrossRef]
  135. Bonder, M.J.; Kurilshikov, A.; Tigchelaar, E.F.; Mujagic, Z.; Imhann, F.; Vila, A.V.; Deelen, P.; Vatanen, T.; Schirmer, M.; Smeekens, S.P.; et al. The effect of host genetics on the gut microbiome. Nat. Genet. 2016, 48, 1407–1412. [Google Scholar] [CrossRef]
  136. Flint, H.J.; Duncan, S.H.; Scott, K.P.; Louis, P. Links between diet, gut microbiota composition and gut metabolism. Proc. Nutr. Soc. 2014, 74, 13–22. [Google Scholar] [CrossRef] [PubMed][Green Version]
  137. Zoetendal, E.G.; de Vos, W.M. Effect of diet on the intestinal microbiota and its activity. Curr. Opin. Gastroenterol. 2014, 30, 189–195. [Google Scholar] [CrossRef] [PubMed]
  138. Lordan, C.; Thapa, D.; Ross, R.P.; Cotter, P.D. Potential for enriching next-generation health-promoting gut bacteria through prebiotics and other dietary components. Gut Microbes 2020, 11, 1–20. [Google Scholar] [CrossRef] [PubMed][Green Version]
  139. Plamada, D.; Vodnar, D.C. Polyphenols—Gut Microbiota Interrelationship: A Transition to a New Generation of Prebiotics. Nutrients 2021, 14, 137. [Google Scholar] [CrossRef] [PubMed]
Figure 1. A schematic illustration listing the bacteria that can synthesize B vitamins and the effects of B vitamin deficiencies on gut health.
Figure 1. A schematic illustration listing the bacteria that can synthesize B vitamins and the effects of B vitamin deficiencies on gut health.
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Hossain, K.S.; Amarasena, S.; Mayengbam, S. B Vitamins and Their Roles in Gut Health. Microorganisms 2022, 10, 1168.

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Hossain KS, Amarasena S, Mayengbam S. B Vitamins and Their Roles in Gut Health. Microorganisms. 2022; 10(6):1168.

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Hossain, Khandkar Shaharina, Sathya Amarasena, and Shyamchand Mayengbam. 2022. "B Vitamins and Their Roles in Gut Health" Microorganisms 10, no. 6: 1168.

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