Abstract
Probiotic has modernized the current dietetic sense with novel therapeutic and nutritional benefits to the consumers. The presence of bile salt hydrolase (BSH) in probiotics renders them more tolerant to bile salts, which also helps to reduce the blood cholesterol level of the host. This review focuses on the occurrence of bile salt hydrolase among probiotics and its characterization, importance, applications, and genetics involved with recent updates. Research on bile salt hydrolase is still in its infancy. The current perspective reveals a huge market potential of probiotics with bile salt hydrolase. Intensive research in this field is desired to resolve some of the lacunae.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Bile salt hydrolase (BSH) is an enzyme produced by several bacterial species in the human or animal gastrointestinal tract that catalyzes the glycine- or taurine-linked bile salt deconjugation reaction. Since bile acts as a biological detergent by which it shows antimicrobial property, microbes produce BSH against it to cope up with its toxicity. Microbial BSH activity contributes for its probiotic properties in the gastrointestinal tract; however, the precise mechanism is not evident.
Bile consists of cholesterol, bile acids (glycocholic and taurocholic acid), phospholipids, water, and pigment biliverdin [1–3]. It is produced as a yellow or green aqueous solution in pericentral hepatocytes from the liver of most vertebrates. Bile salts are composed of a hydrophilic side and a hydrophobic side. Hence, they tend to aggregate to form micelles; the hydrophobic sides combine towards the center and hydrophilic sides towards the outside. In the center of these micelles are triglycerides, which are separated from a larger globule of lipid. The solubility of the hydrophobic steroid nucleus is improved by conjugation with either glycine (glycoconjugated) or taurine (tauroconjugated) prior to synthesis. Consequently, the resulting molecules are amphipathic, which can solubilize the lipids to form mixed micelles.
The human liver can produce close to 1 l of bile every day, but comparatively small amounts are lost from the body. Hence, approximately 95% of the bile acids distributed to the duodenum are reabsorbed into venous blood within the ileum, and subsequently, through the sinusoids of the liver, they arrive at the portal vein. Hepatocytes remove the bile acids capably from sinusoidal blood, but small amounts run off into systemic circulation. Bile acids are afterward transported across the hepatocytes to be resecreted into canaliculi. As a whole, the enterohepatic recirculation makes each bile salt molecule available several times during a solitary digestive stage. During these processes, an important biotransformation that must take place before subsequent modifications is termed deconjugation [4], catalyzed by the BSH. The resulting molecules are termed as unconjugated or deconjugated bile acids. Thus, bile salt tolerance is a desired property for probiotic, which comes due to BSH activity. Ordinarily, the concentration of bile salts in bile is 0.8%. Bile also emulsifies and solubilizes the lipids prior to fat digestion.
Probiotic offers several nutritional and therapeutic benefits to consumers without any side effects, which has made them popular among consumers. It has become a popular ingredient, especially in milk products, viz., ice-cream, yogurt, cheese, etc., more specifically in developed countries where educated folk prefer probiotic-based diets. Today, health practitioners prescribe probiotic to patients very commonly to restore gut-flora after antibiotic episodes. Probiotics are dietary supplements and live microorganisms containing potentially beneficial bacteria or yeasts, which also refer to a kind of nutritional therapy based on eating probiotic foods and dietary supplements. The microorganisms referred are non-pathogenic bacteria and are considered “friendly germs” due to the benefits they offer to the gastrointestinal tract and immune system. Most studied probiotics are from the genera of Lactobacillus sp. [5–8] and Bifidobacterium sp. [9, 10]. Less commonly, strains of Enterococcus sp. [11] Escherichia coli [12], Leuconostoc sp. [13], Pediococcus sp. [14], Saccharomyces sp. [15], Bacillus sp. [16–19], Sporolactobacillus, Brevibacillus, and Streptococcus sp. [20], and other non-dairy probiotics [21] have also been used.
Probiotics bring out dietetic means to support the balance of intestinal flora. They may be used to counteract the local immunological dysfunctions [22], improve mineral absorption [23], reduce blood pressure [24], reduce serum cholesterol concentration [25], reduce allergy [26, 27], stimulate phagocytosis by peripheral blood leucocytes [28], modulate cytokine gene expression [29], have adjuvant effects or vaccinate [30], regress tumors [31], reduce carcinogen or co-carcinogen production, stabilize the gut mucosal barrier function, and prevent infectious succession of pathogenic microorganisms [32], and influence intestinal metabolism [33].
The probiotic business runs into millions of dollars spread over the USA, Canada, Japan, Europe, Asia-Pacific, Middle-East, and Latin America. There are as many as 121 leading companies worldwide, including BioGaia Biologics AB, Chr. Hansen A/S, Danisco A/S, Groupe Danone, Institut Rosell, Lifeway Foods, Natren, Nestlé Nutrition, Probi AB, Seven Seas Ireland, Stonyfield Farm, Valio, and Yakult Honsha. Multibionta from Yakult was the first clinically proved multivitamin probiotic. Howaru (from Danisco) launched for gut health, Calpis against tooth decay, and Kirin-Noale against blood pressure are some other commercial probiotic brands.
A variety of probiotics with BSH have been recognized and characterized. Bile salt tolerance has generally been considered more important during probiotic selection in Bifidobacterium than that of the other properties, such as gastric and pancreatic tolerance. It has also been observed that pancreatin supported Bifidobacterium possesses natural tolerance to survive in the gastrointestinal tract and resist against the antimicrobial property of bile acids [34]. Bile salt tolerance of some microorganisms is possibly due to the presence of BSH and some transporter proteins, which are functionally related to each other to respond efficiently to the stress from bile salts [35]. Microbial traits, which would be expected to be appropriate for survival in the human gut, must be proficient to pathogens for bile resistance [36]. Jones et al. [37] hypothesized that BSH facilitates colonization by mediating the resistance to the conjugated bile acids (CBA).
The aim of the present study was to review the recent advances on probiotic BSH enzymes, including the biological significance of its production and utilization, and briefly demonstrate the impact of bile hydrolysis on human physiology. Future prospects and possible applications of BSH research are also discussed.
Bile Salt Hydrolase (BSH)
BSH containing probiotic strains are preferred over BSH-negative strains as they help in cholesterol removal. BSHs belong to the choloylglycine hydrolase enzymes family, which also comprises penicillin amidases (EC-3.5.1.11). Both have been classified as an N-terminal nucleophilic (Ntn) hydrolase with an N-terminal cysteine residue. BSH (cholylglycine hydrolase; EC-3.5.1.24) catalyzes the hydrolysis of amide bond in conjugated bile salts (CBS); consequently, free amino acids are released, which form the deconjugated bile acid (mainly cholic and quenodeoxycholic). These primary bile acids may afterward undergo 7α-dehydroxylation and get converted into secondary bile acids (deoxycholic and lithocholic) [38]. The conjugated salts of cholic acid (for which no deconjugation is found) are more toxic than the conjugated salts of deoxycholic acid for which the deconjugation occurs.
BSHs can identify its substrate (bile acids) on amino acid groups (glycine/taurine) and also on cholate steroid nucleus. There have been a number of reports on cholate group identification by BSH. Several descriptions have supported its recognition by most BSHs at amino acid moieties and the hydrolysis of glycoconjugated bile salts that are more efficient than the tauroconjugated bile salts [39–41]. A Lactobacillus buchneri JCM1069 exhibited hydrolase activity against the taurodeoxycholic acid but not against the taurocholic acid, although both acids had taurine as their amino acid moiety but varied in their steroid moieties at 7α position [42]. Mc Auliffe et al. [43] turned off bshA gene of Lactobacillus acidophilus NCFM, which decreased the ability to hydrolyze the chenodeoxycholic containing bile salts, e.g., taurochenodeoxycholic acid (TCDCA) and glycochenodeoxycholic acid (GCDCA).
In order to survive well, the bacteria perform their metabolic activities to acquire the beneficial growth, and their genomes tend to possess diverse BSHs, which may confer additional advantages. BSHs are very specific for certain bile types, and their duration of contact to bile ensures the bacterial survival into varying bile environments. Studies carried out in Lactobacillus plantarum WCFS1, which had four bsh genes, and L. acidophilus NCFM, which had two bsh genes, supported this assumption [43, 44]. Bile addition may sometimes have inducing or inhibiting effects on BSHs as they are highly substrate-specific. Studies have shown that the expression of bsh 1 by the bile was induced ∼sixfold, while of bsh 3 was reduced ∼fivefold. Two bsh genes of L. acidophilus NCFM were inactivated, which indicated that the encoded enzymes possessed different substrate specificities [44]. It is also known that different parts of bile stimulate different BSHs. BSH A activity was stimulated by the steroid nucleus of bile salts, while the activity of BSH B was induced by the amino acid side chain [43].
Studies have also been conducted on the structure of BSHs which exhibited slight differences. The crystal structure of BSH from Bifidobacterium longum revealed that it was a member of the N-terminal nucleophil hydrolase superfamily, possessing the characteristic αββα tetra-lamellar tertiary structure arrangement in it, and also demonstrated the evolutionary relationship with penicillin V acylase [45]. Other amino acids, viz. Asp-20, Tyr-82, Asn-175, and Arg-228 are believed to take part actively along with Cys in catalysis of bile salts. Rosocha et al. [46] made the structural comparison of BSH in Clostridium perfringens with other members of Ntn hydrolase family and found them very well conserved in the geometry of active sites [46]. BSH from Bifidobacterium showed the tetrameric structure with native molecular weight ranging between 125,000 to 150,000 and 35,024 of its subunit molecular weight. The SH group in the N-terminal cysteine was responsible for BSH activity of Bifidobacterium bifidum [40, 41]. This is the reason that BSH are vigorously inhibited by thiol enzyme inhibitors. The substitution of Cys with Ser or Thr results in an inactive enzyme, which emphasizes the importance of the presence of cysteine. BSH can hydrolyze all the six major human bile salts and at least two animal bile salts [41]. Bifidobacterium also embraces the diverse BSH types A, B, and C. The isoelectric point of BSH type B from B. bifidum ATCC 11863 was 4.45; other BSH (types A and C) had pI values approx. 4.65. N-terminal amino acid sequencing of types A and C BSH revealed that six out of 20 amino acid residues were unalike and highly conserved. All the BSH from five strains showed a better deconjugation rate on glycine-conjugated bile salts than that of taurine-conjugated forms [40]. Two different antigenic conjugated BSHs, viz. α and β had been expressed from Lactobacillus johnsonii strain 100–100 that combined to form native homo- and heterotrimers [47]. The alignment of BSH protein sequence of probiotic strains revealed that many probiotics acquired more than one BSH homolog [48].
BSHs described in several probiotic organisms have been produced at intracellular space, exhibited pH maxima in acidic range (5.0–6.0), and have been purified [40, 41, 49–51]. A thermophilic Brevibacillus sp. has been reported, producing BSH (56 kDa, homodimer), hydrolyzing all of the six major human bile salts. The enzyme preferred glycine-conjugated substrates with apparent K m and k cat values of 3.08 μM and 6.32 × 102 s−1, respectively, for glycodeoxycholic acid [52]. A comparatively lower molecular weight BSH (37 kDa) was purified from L. plantarum CK102, which maximally hydrolyzed the glycocholate with apparent K m and V max values of 0.5 mM and 94 nmol/min/mg, respectively, at pH values between 5.8 and 6.3. This activity was greatly inhibited by iodoacetate and periodic acid [53].
The immobilization of BSH has also been tried out for the economic utilization in both ways, that is, the protein and the organism itself. BSH isolated from L. buchneri ATCC 4005 was immobilized in 0.5% gellan gum gel [54]. BSH, microencapsulated by food-grade whey protein-gum arabic, was compared for its efficacy with living L. plantarum WCFS1 in vitro that would produce BSH endogenously. BSH efficacy was better against pancreatin and low gastric pH initially, but its activity decreased further due to proteolytic degradation, whereas L. plantarum WCFS1 withstood such conditions [55]. For the first time, the BSH active strains, Lactobacillus reuteri and B. longum, were immobilized by micro-encapsulation [56].
Occurrence of BSH Among Probiotics
BSH activity has been found mostly in Gram-positive commensals (except a few Bacteroides), and they also acquire genome homolog, whereas it is lacking in Gram-negative commensals of the gastrointestinal tract. Escherichia coli and Salmonella enterica serovar typhimurium are reported as BSH-negative strains [57]. The prevalence of BSH is well recognized among the established probiotic genera. It is reported foremost in the majority of species from genera Lactobacillus [43, 47, 50, 58–63], Bifidobacterium [34, 35, 40, 61, 64], Bacteroides [51], and Enterococcus [65–67]. Tanaka et al. [60] screened more than 300 strains from Bifidobacterium, Lactobacillus, Lactococcus lactis, Leuconostoc mesenteroides, and Streptococcus thermophilus and found BSH activity in 273 strains in Bifidobacterium and Lactobacillus but missing in L. lactis, L. mesenteroides, and S. thermophilus [60].
Both Lactobacillus and Bifidobacterium strains are used regularly as safe probiotics. Other probiotic species are also commensal residents of the gastrointestinal tracts of vertebrates and exhibit positive effects in limited aspects, seeking their suitable niche in the world probiotic market.
Among the several isolates of acid- (pH 2.5 and 3.0) and bile- (0.3% oxgall) tolerant strains from Streptococcus (61.1%), Lactobacillus (71.8%), and Bifidobacterium (27.9%) genera, three strains, Streptococcus HJS-1, Lactobacillus HJL-37, and Bifidobacterium HJB-4, were BSH-positive probiotic strains [61]. Schillinger et al. [62] detected BSH activity in various strains of L. acidophilus and L. johnsonii but not in Lactobacillus casei strains group. These lactobacilli showed various degrees of adherence on HT29 MTX cells and on human collagen type IV, fibrinogen, and fibronectin as well [62]. However, L. lactis and S. thermophilus isolated from bile-salt-originated environments and from outside the gut did not exhibit such activity [42, 59, 68].
Lactobacilli were principal genera among the gut microbiota leading the maximum BSH activity in mice gut, which was proved by eliminating the lactobacilli from the total gut microbiota. It was an ideal bile salt whose hydrolase activity was reduced by 86% and was larger than 98% when both lactobacilli and enterococci were eliminated [69]. High levels of BSH activity have been reported in enterococci genus [66, 70]. Intracellular BSH production at higher temperature was reported in thermophilic Brevibacillus spp. [52, 71]. Table 1 shows several important BSH-positive strains from diverse bacterial genera.
Molecular and Expression Studies of BSH Genome
Microbial genetics have not been explored enormously in order to get the adequate information about BSH evolution in various genera. Various studies have reported diverse BSH homologs in Lactobacillus, Bifidobacterium, and other genera using molecular technique-based approaches. There is little information about its constitutive or inductive conservation or mode of gene transfer. Metagenomic approaches have been exploited to identify the functional BSH in all the major gut-associated bacterial divisions and archaeal species, which have shown that BSHs are enriched in the human gut microbiome. Phylogenetic studies have explained their selection pressure in the form of conjugated bile acid, which has driven the evolution of members of the Ntn_CGH-like protein family towards BSH activity [37].
There has been little information regarding BSH genetic evolution between various genera. Lambert et al. [72] predicted L. plantarum WCFS1 genetics, carrying four bsh genes (bsh1, bsh2, bsh3, and bsh4), where only bsh1 exhibited the majority of its BSH activity and the other genes appeared to be conserved. These conserved genes might be involved to encode penicillin V acylase rather than BSH activity and responsible for its physiology and mode of living [72]. Attainment of the bsh gene takes place by horizontal (lateral) gene transfer in lactobacilli [59]. A similar mechanism of gene transfer has been observed in Listeria monocytogenes [73]. Apart from the constitutive BSH production, plasmid-mediated activity of BSH in L. acidophilus, L. plantarum, Lactobacillus brevis, and Lactobacillus fermentum has also been observed [74]. However, there is no clear information of gene transfer in Bifidobaterium.
The nucleotide sequence of the BSH gene of L. acidophilus PF01 was analyzed, which revealed its location and showed that it was surrounded by 951 nucleotides in a single open reading frame (ORF) and encoding a 316 amino acid protein. BSH promoter was located upstream of the start codon. The expressed protein exhibited high homology with BSHs from other source organisms. Four amino acid motifs FGRNXD, AGLNF, VLTNXP, and GXGXGXXGXPGD, located around the active site, were highly conserved. The BSH gene was cloned into the pET21b expression vector and expressed in E. coli BLR (DE3). The purified recombinant BSH enzyme exhibited hydrolase activity against tauroconjugated bile salts, but not against the glycoconjugated bile salts [39]. Two genes, bshA and bshB, have been identified encoding BSH in the genome sequence of L. acidophilus NCFM, where different substrate specificities of two enzymes were observed [43].
Vector-free engineering on L. plantarum by chromosomal integration of an exogenous gene without inactivation of physiological traits has been reported [75]. Lactobacillus plantarum cbh gene, encoding the conjugated BSH, was cloned and successfully expressed in the heterologous host L. casei LK1 with the aid of pSMA23-derived vectors [76]. BSH genes (bsh) of B. longum was cloned and expressed in E. coli. Expressed BSH protein was employed for further biochemical studies under thermal, chemical, and pH-mediated denaturation conditions prior to get the information of active site, mechanism of bile hydrolysis, and BSH properties [77].
Scope of Probiotic BSH on Host Health
Cholesterol Lowering Property
Today, hypercholesterolemia is a major challenge for human health worldwide and a central cause of coronary heart diseases. It is treated with pharmacological drugs, which are very expensive and cause a number of redundant side effects. Probiotic-based oral therapy has proved remarkable efficacy to reduce the blood cholesterol level up to 33% [58, 77–79], where BSH activity is significantly liable for the benefit. Human feces isolate L. plantarum CK 102 has been found to reduce the blood cholesterol level, triglyceride, LDL-cholesterol, and free-cholesterol in rats [80]. Cholesterol lowering activity of BSH by probiotic organisms has been widely discussed [54, 81]. Cell free supernatant from L. acidophilus ATCC 43121 exhibited cholesterol removing activity, which was different from earlier reports, suggesting this mechanism from live cells. The molecular mass of a protein with cholesterol-removing activity was estimated at 12 kDa [82]. Infant feces isolate L. plantarum PH04 was able to reduce the serum cholesterol and triglycerides to levels of 7% and 10%, respectively, when it was fed to hyper-cholesterolemic mice at numbers of 107 CFU per mouse per day for 14 days [83]. Lactobacillus acidophilus strains isolated from Maasai traditional fermented milk “Kule naoto” showed BSH activity and exhibited the ability to assimilate the cholesterol in vitro [84]. Sridevi et al. [54] fed Wistar rats with the immobilized Lactobacillus BSH, which induced hypercholesteremia by triton X-100. The serum cholesterol and triglycerides were reduced by 50% and 15%, respectively, in the group fed with immobilized enzyme at 10 IU/kg dose, whereas administration of 20 IU/kg immobilized enzyme resulted in the reduction of serum cholesterol and triglycerides by 58% and 45%, respectively [54].
Nutritional Relevance and Substrate Specificity
Bile salt deconjugation process generates amino acids, which serve as a carbon, nitrogen, and energy sources. Glycine is hydrolyzed into ammonia and carbon dioxide, whereas taurine is hydrolyzed into ammonia, carbon dioxide, and sulfate. Bile salt deconjugations take place by BSH-positive strains that confer a nutritional advantage. Deconjugation of taurocholate (TCA) and glycocholate (GCA) has been reported in L. acidophilus SNUL020 and SNUL01 at similar rates, whereas L. acidophilus FM01 deconjugated the GCA more rapidly than TCA [68]. Van [85] also supported this hypothesis; he found that certain BSH-positive clostridium strains utilized the liberated taurine as an electron acceptor and exhibited improved growth in the presence of taurine or taurine-conjugated bile salts in the medium.
Modification of Membrane Integrity
Some of the friendly bacteria are important for host gut health and their hydrolytic enzymes, viz. lysozyme, phospholipase A2, α-defensins, etc., are key bio-molecules that play a crucial role in intestinal defense. Survival of these microbes in the gut conditions is pretty challenging where compositional integrity, permeability, fluidity, hydrophobicity, and net charge of membranes establish the degree of strength against the host defenses [86]. Studies have revealed the involvement of BSHs for carrying out bile or cholesterol integration into bacterial cell membranes, which then augment further potency of the membranes by BSH-mediated lipid intermolecular hydrogen bonding [87–89], or could amend its fluidity or charge. These modifications take place due to BSH activity that recommends safety against the perturbation of the configuration and integrity of bacterial membranes by the immune system that ensures to set up the prolonged persistence. This mechanism confers BSH-positive bacteria to dominate over the BSH-negative pathogens or other transients.
Bile Detoxification/Deconjugation
Both bile salt hydrolysis and bile tolerance envelop separate ambiguity in bile science. Bile acids are potentially toxic end products of cholesterol metabolism. Several studies undertaken using the wild-type and bsh mutant combinations recognize a connection between the bile salt hydrolysis and bile tolerance in probiotics organisms. Mutant isolate Lactobacillus amylovorus (modified with N-methyl-N 1-nitro-N-nitrosoguanidine mutagenesis), in which BSH activity was partly reduced, exhibited reduced growth rates in the presence of bile salts [50]. Mutation of bsh in L. monocytogenes and [73] L. plantarum [58] made their cells more susceptible to bile salts. There are reports comparing the susceptibility of few bifidobacterial strains with conjugated primary (glycocholate and taurocholate) and secondary (glycodeoxycholate and taurodeoxycholate) salts. The level of the hydrolase activity with acquired bile resistance was found, and it was found that none of them displayed deconjugation against the primary salts, while most of them deconjugated the secondary salts [90]. The accurate BSH mechanism by which the bacteria exhibit the tolerance against bile is not yet known. However, it was proposed that the protonated form of bile salts might exhibit toxicity through intracellular interface, and BSH-positive cells might protect themselves by the formation of the weaker unconjugated counterparts [58]. This mechanism could facilitate to wipe out the acidification by bringing back and exporting the co-transported proton [58].
Microcapsulation of probiotic cells has also been attempted to achieve better BSH deconjugation rates. Lactobacillus reuteri microcapsules, which metabolize glyco- and tauroconjugated bile salts at rates of 10.16 ± 0.46 and 1.85 ± 0.33 μmol/g microcapsule per hour, respectively, showed better acid resistance, whereas B. longum showed low BSH activity and acid resistance. Lactobacillus reuteri microcapsules also exhibited an improved deconjugation with 49.4 ± 6.21% of glycoconjugates per hour in a simulated human gastrointestinal (GI) model and complete deconjugation after 4 h [56]. Bile salt deconjugation rates of microencapsulated BSH overproducing cells of L. plantarum 80 were 4.87 ± 0.28 μmol/g microcapsule per hour towards glycoconjugates and 0.79 ± 0.15 μmol/g microcapsule per hour towards tauroconjugates in the simulated gastro-intestine [91].
Improvement in GIT Condition
Intestinal bacteria have been reported to be involved in the production of secondary bile acids (via successive unconjugated bile salts modifications), which were accumulated in the entero-hepatic circulation of some individuals and caused gallstones, gastrointestinal tract (GIT) dysfunctions, colon cancer, and other GIT diseases. Kurdi et al. [92] studied the cholic acid transportation and accumulation in B. bifidum and showed that cholic acid (liberated bile acid from BSH) accumulated inside the bacterial cell in the host intestine. The entrapment of these free bile acids by bifidobacteria resulted in the decreased assembly of secondary bile acids, which were usually considered as cytotoxic and precarcinogenic [92]. The responsible enzyme (7α-dehydroxylase) was found in Clostridium and Eubacterium species [93, 94] but not in lactic acid bacteria or bifidobacteria [92]. The majority of the intestinal anaerobic bacteria were involved in bile salt hydrolysis and hydroxyl group dehydrogenation reactions.
Reduction in Lipid Digestion
Conjugation of bile salts is a significant step prior to lipid assimilation in mammals. Bile acid deconjugation in mammalian intestine was eventually found to facilitate the intestinal bacteria [95], which is an undesired process for lipid digestion. Microbial deconjugation and dehydroxylation of conjugated bile salts by BSH-positive bacteria upset the digestion process, which results in related complications and abnormal growth. A product of microbial bile acid biotransformation in host intestine was found to be the main cause of growth reduction in chicks [96]. Microbial deconjugation and dehydroxylation of bile acids also mess up lipid assimilation in the host [97, 98]; moreover, it produces toxic products to facilitate the impaired growth [99]. Further studies anticipated the action of an antibiotic that plays a crucial role in the inhibition of microbial bile acid biotransformation in GIT and also proposed an opposite correlation between the level of cholyltaurine hydrolysis and growth rate of antibiotics fed broiler chickens in their small intestine [100, 101]. This growth reduction was reversible with antibiotic supplementation [102].
Future Prospects
Bile acid biotransformation studies have insights via crystallization, site-directed mutagenesis, and protein secondary structure analysis. Molecular cloning of genes encoding bile salt-biotransforming enzymes has assisted getting a closer view of the genetic association of related pathways and aided developing the probes for the detection of bile salt-modifying bacteria. The potential exists for altering the bile acid pool by targeting the key enzymes in the 7α/β-dehydroxylation pathway through the development of pharmaceuticals or sequestering the bile acids biologically in probiotic bacteria, which may result in their effective removal from the host after excretion [103].
Upcoming research on BSH enzymes must contemplate on determining their specific role in gastrointestinal flora, and beneficial or detrimental effects on the host as well. BSH research must spotlight a cooperative account between the BSH mutants and BSH-positive strains in the perspective of its significance for the host animal. Investigations must focus on determining the morphological (membrane integrity of bile and cholesterol or in terms of fatty acids composition) and histological changes in the organism mounting in the presence or absence of bile salts. Moreover, the ultimate providence of the final product synthesized via bile salt hydrolysis should be examined. Animal trials would provide better insights to uncover its role in gastrointestinal endurance. Most importantly, secondary bile acid levels in serum and biliary must be examined during the hydrolysis in the bile acid pool as it is considered as cytotoxic and precarcinogenic for colon cancer. It also leads to DNA damage, colonic mucosal dysfunction, and, ultimately, diarrhea [104, 105]. Gallstone patients have been observed with elevated secondary bile salt concentrations [106, 107]. Molecular tools, such as reverse transcriptase-polymerase chain reaction (PCR), should be used to quantify BSH homologs and trace heterologous or homologous BSH incidence. Blotting techniques, microarray, metagenomics, denaturing gradient gel electrophoresis, and fluorescence in situ hybridization can be used to monitor the BSH-positive strains and their synergistic or individual impact on host health and established gut micro flora after the administration.
BSH research should lead to extensive isolation of BSH-positive microorganisms and their characterization and construct an approach to improve these strains prior to their prolonged persistence in GIT for better performances. Screening of bsh gene can be performed using PCR with degenerative primers, and thereafter, determining their potency using well-known simplified assay methods [74]. This could have a major perspective, especially by appealing to the budding health-conscious civilization as the intake of a probiotic-based diet might be more “promising” than the existing cholesterol-removing therapies.
Conclusion
The importance of BSH seems apparent to confer the additional benefits from novel probiotic organisms to the host when it is administered in highly adverse conditions of GIT. BSH research still in its infancy and future investigations may uncover its significance more clearly. BSH research may eventually lead to inspecting more vigorous probiotics with better health performance.
References
Carey, M. C., & Duane, W. C. (1994). In I. M. Arias, N. Boyer, N. Fausto, W. B. Jackoby, D. A. Schachter & D. A. Shafritz (Eds.), Enterohepatic circulation. The liver: Biology and pathobiology (pp. 719–738). New York: Raven.
Hofmann, A. F. (1994). In I. M. Arias, J. L. Boyer, N. Fausto, W. B. Jackoby, D. A. Schachter & D. A. Shafritz (Eds.), Bile acids. The liver: Biology and pathobiology (pp. 677–718). New York: Raven.
Bahar, R. J., & Andrew, S. (1999). Bile acid transport. Gastroenterology Clinics of North America, 28, 27–58.
Batta, A. K., Salen, G., Arora, R., Shefer, S., Batta, M., & Perseon, A. (1990). Side chain conjugation prevents bacterial 7α-dehydroxylation of bile acids. The Journal of Biological Chemistry, 265, 10925–10928.
Wang, K. Y., Li, S. N., Liu, C. S., Perng, D. S., Su, Y. C., & Wu, D. C. (2004). Effects if ingesting Lactobacillus and Bifidobacterium containing yogurt in subjects with colonized Helicobacter pylori. The American Journal of Clinical Nutrition, 80, 737–741.
Cruchet, S., Obregon, M. C., Salazar, G., Diaz, E., & Gotteland, M. (2003). Effect of the ingestion of a dietary product containing Lactobacillus johnsonii La1 on Helicobacter pylori colonization in children. Nutrition, 19, 716–721.
Macedo, R. F., Freitas, R. J. S., Pandey, A., & Soccol, C. R. (1999). Production and shelf-life studies of low cost beverage with soymilk, buffalo cheese whey and cow milk fermented by mixed cultures of Lactobacillus casei ssp. shirota and Bifidobacterium adolescentis. Journal of Basic Microbiology, 39(4), 243–251.
de Reque, E. F., Pandey, A., Franco, S. G., & Soccol, C. R. (2000). Isolation, identification and physiological study of Lactobacillus fermentum LPB for use as probiotics in chickens. Review of Microbiology, 31, 303–307.
Weizman, Z., Asli, G., & Alsheikh, A. (2005). Effect of a probiotics infant formula on infections in child care centers: comparison of two probiotics agents. Pediatrics, 115, 5–9.
O’Mahony, L., McCarthy, J., Kelly, P., Hurley, G., Luo, F., Chen, K., et al. (2005). Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology, 128, 541–551.
Reid, G., & Bruce, A. W. (2006). Probiotics to prevent urinary tract infections: the rationale and evidence. World Journal of Urology, 24, 28–32.
Tromm, A., Niewerth, U., Khoury, M., Baestlein, E., Wilhelms, G., Schulze, J., et al. (1917). The probiotics E. coli strain Nissle 1917 for the treatment of collagenous colitis: first results of an open-label trial. Zeitschrift fur Gastroenterologie, 42, 365–369.
Chung, C. H., & Day, D. F. (2004). Efficacy of Leuconostoc mesenteroides ATCC 13146 iso-malto-oligosaccharides as poultry prebiotic. Poultry Science, 8, 1302–1306.
Park, J. H., Seok, S. H., Cho, S. A., Baek, M. W., Lee, H. Y., Kim, D. J., et al. (2005). Antimicrobial effect of lactic acid producing bacteria culture condensate mixture (LCCM) against Salmonella enteritidis. International Journal of Food Microbiology, 101, 111–117.
Kurugol, Z., & Koturoglu, G. (2005). Effects of Saccharomyces boulardii in children with acute diarrhoea. Acta Paediatrica, 94, 44–47.
Hoa, T. T., Duc, L. H., Isticato, R., Baccigalupi, L., Ricca, E., Van, P. H., et al. (2001). Fate and dissemination of Bacillus subtilis spores in a murine model. Applied and Environmental Microbiology, 67, 3819–3823.
Patel, A. K., Ahire, J. J., Pawar, S. P., Chaudhari, B. L., & Chincholkar, S. B. (2009). Comparative accounts of probiotic characteristics of Bacillus spp. isolated from food wastes. Food Research International, 42, 505–510.
Patel, A. K., Deshattiwar, M., Chaudhari, B. L., & Chincholkar, S. B. (2009). Production, purification and chemical characterization of the catecholate siderophore from potent probiotic strains of Bacillus spp. Bioresource Technology, 100, 368–373.
Patel, A. K., Ahire, J. J., Pawar, S. P., Chaudhari, B. L., Shouche, Y. S., & Chincholkar, S. B. (2009). Evaluation of probiotic characteristics of siderophoregenic Bacillus spp. isolated from dairy waste. Applied Biochemistry and Biotechnology. doi:10.1007/s12010-009-8583-2
Burton, J. P., Wescombe, P. A., Moore, C. J., Chilcott, C. N., & Tagg, J. R. (2006). Safety assessment of the oral cavity probiotics Streptococcus salivarius K12. Applied and Environmental Microbiology, 72, 3050–3053.
Prado, F. C., Parada, J. L., Pandey, A., & Soccol, C. R. (2008). Trends in non-dairy probiotic beverages. Food Research International, 41, 111–123.
Bujalance, C., Moreno, E., Jimenez-Valera, M., & Ruiz-Bravo, A. (2007). A probiotics strain of Lactobacillus plantarum stimulates lymphocyte responses in immunologically intact and immunocompromised mice. International Journal of Food Microbiology, 113, 28–34.
Famularo, G., De Simone, C., Pandey, V., Sahu, A. R., & Minisola, G. (2005). Probiotics lactobacilli: an innovative tool to correct the mal-absorption syndrome of vegetarians?. Medical Hypotheses, 65(6), 1132–1135.
Yamano, T., Tanida, M., Niijima, A., Maeda, K., Okumura, N., Fukushima, Y., et al. (2006). Effects of the probiotics strain Lactobacillus johnsonii strain La1 on autonomic nerves and blood glucose in rats. Life Science, 79, 1963–1967.
Sanders, M. E. (2000). Considerations for use of probiotics bacteria to modulate human health. The Journal of Nutrition, 130, 384S–390S.
Kirjavainen, P. V., Salminen, S. J., & Isolauri, E. (2003). Probiotics bacteria in the management of atopic disease: underscoring the importance of viability. Journal of Pediatric Gastroenterology and Nutrition, 36, 223–227.
Kalliomaki, M., Salminen, S., Poussa, T., Arvilommi, H., & Isolauri, E. (2003). Probiotics and prevention of atopic disease: 4-year follow-up of a randomized placebo-controlled trial. Lancet, 361, 1869–1871.
Reid, G., Jass, J., Sebulsky, M. T., & McCormick, J. K. (2003). Potential uses of probiotics in clinical practice. Clinical Microbiology Reviews, 16, 658–672.
Kim, D. H., & Austin, B. (2006). Cytokine expression in leucocytes and gut cells of rainbow trout, Oncorhynchus mykiss Walbaum, induced by probiotics. Veterinary Immunology and Immunopathology, 114, 297–304.
Grangette, C., Muller-Alouf, H., Goudercourt, D., Geoffroy, M., Turneer, M., & Mercenier, A. (2001). Mucosal immune responses and protection against tetanus toxin after intranasal immunization with recombinant Lactobacillus plantarum. Infection and Immunity, 69, 1547–1553.
Brady, L. J., Gallaher, D. D., & Busta, F. F. (2000). The role of probiotic cultures in the prevention of colon cancer. The Journal of Nutrition, 130, 410S–414S.
Hamilton-Miller, J. M. T. (2003). The role of probiotics in the treatment and prevention of Helicobacter pylori infection. International Journal of Antimicrobial Agents, 22, 360–366.
Xu, J., Bjursell, M. K., Himrod, J., Deng, S., Carmichael, L. K., Chiang, H. C., et al. (2003). A genomic view of the human-Bacteroides thetaiotaomicron symbiosis. Science, 299, 2074–2076.
Masco, L., Crockaert, C., Van Hoorde, K., Swings, J., & Huys, G. (2007). In vitro assessment of the gastrointestinal transit tolerance of taxonomic reference strains from human origin and probiotic product isolates of Bifidobacterium. Journal of Dairy Science, 90, 3572–3578.
Kim, G. B., & Lee, B. H. (2008). Genetic analysis of a bile salt hydrolase in Bifidobacterium animalis subsp. lactis KL61. Journal of Applied Microbiology, 105(3), 778–790.
Dethlefsen, L., McFall-Ngai, M., & Relman, D. A. (2007). An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature, 449, 811–818.
Jones, B. V., Begley, M., Hill, C., Gahan, C. G. M., & Marchesi, J. R. (2008). Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. PNAS, 105(36), 13580–13585.
Baron, S. F., & Hylemon, P. B. (1997). In R. I. Mackie & B. A. White (Eds.), Biotransformation of bile acids, cholesterol, and steroid hormones, Vol. I: Gastrointestinal microbiology: Gastrointestinal ecosystems and fermentations (pp. 470–510). New York: Thompson.
Oh, H. K., Lee, J. Y., Lim, S. J., Kim, M. J., Kim, G. B., Kim, J. H., et al. (2008). Molecular cloning and characterization of a bile salt hydrolase from Lactobacillus acidophilus PF01. Journal of Microbiology and Biotechnology, 18(3), 449–456.
Kim, G. B., Yi, S. H., & Lee, B. H. (2004). Purification and characterization of three different types of bile salt hydrolase from Bifidobacterium strains. Journal of Dairy Science, 87, 258–266.
Tanaka, H., Hashiba, H., Kok, J., & Mierau, I. (2000). Bile salt hydrolase of Bifidobacterium longum: biochemical and genetic characterization. Applied and Environmental Microbiology, 66, 2502–2512.
Moser, S. A., & Savage, D. C. (2001). Bile salt hydrolase activity and resistance to toxicity of conjugated bile salts are unrelated properties in lactobacilli. Applied and Environmental Microbiology, 67, 3476–3480.
Mc Auliffe, O., Cano, R. J., & Klaenhammer, T. R. (2005). Genetic analysis of two bile salt hydrolase activities in Lactobacillus acidophilus NCFM. Applied and Environmental Microbiology, 71, 4925–4929.
Bron, P. A., Molenaar, D., De Vos, W. M., & Kleerebezem, M. (2006). DNA micro-array based identification of bile-responsive genes in Lactobacillus plantarum. Journal of Applied Microbiology, 100(4), 728–738.
Kumar, R. S., Brannigan, J. A., Prabhune, A. A., Pundle, A. V., Dodson, G. G., Dodson, E. J., et al. (2006). Structural and functional analysis of a conjugated bile salt hydrolase from Bifidobacterium longum reveals an evolutionary relationship with penicillin v acylase. The Journal of Biological Chemistry, 281, 32516–32525.
Rossocha, M., Schultz-Heienbrok, R., von Moeller, H., Coleman, J. P., & Saenger, W. (2005). Conjugated bile acid hydrolase is a tetrameric N-terminal thiol hydrolase with specific recognition of its cholyl but not of its tauryl product. Biochemistry, 44, 5739–5748.
Elkins, E. A., & Savage, D. C. (1998). Identification of genes encoding conjugated bile salt hydrolase and transport in Lactobacillus johnsonii 100–100. Journal of Bacteriology, 180, 4344–4349.
Begley, M., Hill, C., & Gahan, C. G. M. (2006). Bile salt hydrolase activity in probiotics. Applied and Environmental Microbiology, 72(3), 1729–1738.
Kim, G. B., Brochet, M., & Lee, B. H. (2005). Cloning and characterization of a bile salt hydrolase (bsh) from Bifidobacterium adolescentis. Biotechnology Letters, 27, 817–822.
Grill, J. P., Cayuela, C., Antoine, J. M., & Schneider, F. (2000). Isolation and characterization of a Lactobacillus amylovorus mutant depleted in conjugated bile salt hydrolase activity: relation between activity and bile salt resistance. Journal of Applied Microbiology, 89, 553–563.
Kawamoto, K., Horibe, I., & Uchida, K. (1989). Purification and characterization of a new hydrolase for conjugated bile acids, chenodeoxy-1736, Mini review. Appl. Environ. Microbiol. Cholyltaurine hydrolase from Bacteroides vulgatus. Journal of Biochemistry, 106, 1049–1053.
Sridevi, N., Srivastava, S., Khan, B. M., & Prabhune, A. (2009). Characterization of the smallest dimeric bile salt hydrolase from a thermophile Brevibacillus sp. Extremophiles, 13(2), 363–370.
Ha, C. G., Cho, J. K., Chai, Y. G., Ha, Y. A., & Shin, S. H. (2006). Purification and characterization of bile salt hydrolase from Lactobacillus plantarum CK102. Journal of Microbiology and Biotechnology, 16(7), 1047–1052.
Sridevi, N., Vishwe, P., & Prabhune, A. (2009). Hypocholesteremic effect of bile salt hydrolase from Lactobacillus buchneri ATCC 4005. Food Research International, 42(4), 516–520.
Lambert, J. M., Weinbreck, F., & Kleerebezem, M. (2008). In vitro analysis of protection of the enzyme bile salt hydrolase against enteric conditions by whey protein-gum arabic microencapsulation. Journal of Agricultural and Food Chemistry, 56, 8360–8364.
Martoni, C., Bhathena, J., Urbanska, A. M., & Prakash, S. (2008). Micro-encapsulated bile salt hydrolase producing Lactobacillus reuteri for oral targeted delivery in the gastrointestinal tract. Applied Microbiology and Biotechnology, 81, 225–233.
Begley, M., Sleator, R. D., Gahan, C. G., & Hill, C. (2005). Contribution of three bile-associated loci, bsh, pva, and. btlB, to gastrointestinal persistence and bile tolerance of Listeria monocytogenes. Infection and Immunity, 73, 894–904.
De Smet, I., Hoorde, V. L., Woestyne, V. M., Christiaens, H., & Verstraete, W. (1995). Significance of bile salt hydrolytic activities of lactobacilli. J Appl Bacteriol, 79, 292–301.
Elkins, C. A., Moser, S. A., & Savage, D. C. (2001). Genes encoding bile salt hydrolases and conjugated bile salt transporters in Lactobacillus johnsonii 100–100 and other Lactobacillus species. Microbiology, 147, 3403–3412.
Tanaka, H., Doesburg, K., Iwasaki, T., & Mierau, I. (1999). Screening of lactic acid bacteria for bile salt hydrolase activity. Journal of Dairy Science, 82, 2530–2535.
Lim, H. J., Kim, S. Y., & Lee, W. K. (2004). Isolation of cholesterol-lowering lactic acid bacteria from human intestine for probiotic use. Journal of veterinary science, 5(4), 391–395.
Schillinger, U., Guigas, C., & Holzapfel, W. H. (2005). In vitro adherence and other properties of lactobacilli used in probiotic yoghurt-like products. Int Dairy J, 15(12), 1289–1297.
Maragkoudakis, P. A., Zoumpopoulou, G., Miaris, C., Kalantzopoulos, G., Pot, B., & Tsakalidou, E. (2006). Probiotic potential of Lactobacillus strains isolated from dairy products. Int Dairy J, 16(3), 189–199.
Kim, G. B., Miyamoto, C. M., Meighen, E. A., & Lee, B. H. (2004). Cloning and characterization of the bile salt hydrolase genes (bsh) from Bifidobacterium bifidum strains. Applied and Environmental Microbiology, 70, 5603–5612.
Franz, C. M. A. P., Specht, I., Haberer, P., & Holzapfel, W. H. (2001). Bile salt hydrolase activity of enterococci isolated from food: screening and quantitative determination. Journal of Food Protection, 64, 725–729.
Knarreborg, A., Engberg, R. M., Jensen, S. K., & Jensen, B. B. (2002). Quantitative determination of bile salt hydrolase activity in bacteria isolated from the small intestine of chickens. Applied and Environmental Microbiology, 68, 6425–6428.
Wijaya, A., Hermann, A., Abriouel, H., Specht, I., Yousif, N. M., Holzapfel, W. H., et al. (2004). Cloning of the bile salt hydrolase (bsh) gene from Enterococcus faecium FAIR-E-345 and chromosomal location of bsh genes in food enterococci. Journal of Food Protection, 67, 2772–2778.
Ahn, Y. T., Kim, G. B., Lim, Y. S., Baek, Y. J., & Kim, Y. U. (2003). Deconjugation of bile salts by Lactobacillus acidophilus isolates. Int Dairy J, 13, 303–311.
Tannock, G. W., Dashkevicz, M. P., & Feighner, S. D. (1989). Lactobacilli and bile salt hydrolase in the murine intestinal tract. Applied and Environmental Microbiology, 55(7), 1848–1851.
Yoon, M. Y., Kim, Y. J., & Hwang, H. J. (2008). Properties and safety aspects of Enterococcus faecium strains isolated from Chungkukjang, a fermented soy product. Food Sci Technol, 41(5), 925–933.
Sridevi, N., & Prabhune, A. A. (2009). Source for the production of bile salt hydrolase. Biotechnology, 1–9.
Lambert, J. M., Bongers, R. S., de Vos, W. M., & Kleerebezem, M. (2008). Functional analysis of four bile salt hydrolase and penicillin v acylase family members in Lactobacillus plantarum WCFS1. Applied and Environmental Microbiology, 74(15), 4719–4726.
Dussurget, O., Cabanes, D., Dehoux, P., Lecuit, M., Buchrieser, C., Glaser, P., et al. (2002). Listeria monocytogenes bile salt hydrolase is a virulence factor involved in the intestinal and hepatic phases of listeriosis. Molecular Microbiology, 45, 1095–1106.
Dashkevicz, M. P., & Feighner, S. D. (1989). Development of a differential medium for bile salt hydrolase-active Lactobacillus spp. Applied and Environmental Microbiology, 55, 11–16.
Rossi, F., Capodaglio, A., & Dellaglio, F. (2008). Genetic modification of Lactobacillus plantarum by heterologous gene integration in a not functional region of the chromosome. Applied Microbiology and Biotechnology, 80(1), 79–86.
Sudhamani, M., Ismaiel, E., Geis, A., Batish, V., & Heller, K. J. (2008). Characterisation of pSMA23, a 3.5 kbp plasmid of Lactobacillus casei, and application for heterologous expression in Lactobacillus. Plasmid, 59(1), 11–19.
Kumar, R. S., Suresh, C. G., Brannigan, J. A., Dodson, G. G., & Gaikwad, S. M. (2007). Bile salt hydrolase, the member of Ntn- hydrolase family: Differential modes of structural and functional transitions during denaturation. IUBMB Life, 59(2), 118–125.
Taranto, M. P., Medici, M., Perdigon, G., Ruiz Holgado, A. P., & Valdez, G. F. (1998). Evidence for hypocholesterolemic effect of Lactobacillus reuteri in hypercholesterolemic mice. Journal of Dairy Science, 81, 2336–2340.
Du Toit, M., Franz, C. M., Dicks, L. M., Schillinger, U., Harberer, P., Warlies, B., et al. (1998). Characterization and selection of probiotic lactobacilli for a preliminary mini-pig feeding trial and their effect on serum cholesterol levels, feces pH, and feces moisture content. International Journal of Food Microbiology, 40, 93–104.
Ha, C. G., Cho, J. K., Lee, C. H., Chai, Y. G., Ha, Y. A., & Shin, S. H. (2006). Cholesterol lowering effect of Lactobacillus plantarum isolated from human feces. Journal of Microbiology and Biotechnology, 16(8), 1201–1209.
Kim, G. B., & Lee, B. H. (2005). Biochemical and molecular insights into bile salt hydrolase in the gastrointestinal microflora. Asian-Aus J Anim Sci, 18(10), 1505–1512.
Kim, Y., Whang, J. Y., Whang, K. Y., Oh, S., & Kim, S. H. (2008). Characterization of the cholesterol-reducing activity in a cell-free supernatant of Lactobacillus acidophilus ATCC 43121. Bioscience, Biotechnology, and Biochemistry, 72(6), 1483–1490.
Nguyen, T. D. T., Kang, J. H., & Lee, M. S. (2007). Characterization of Lactobacillus plantarum PH04, a potential probiotic bacterium with cholesterol-lowering effects. International Journal of Food Microbiology, 113, 358–361.
Mathara, J. M., Schillinger, U., Guigas, C., Franz, C., Kutima, P. M., Mbugua, S. K., et al. (2008). Functional characteristics of Lactobacillus spp. from traditional Maasai fermented milk products in Kenya. International Journal of Food Microbiology, 126(12), 57–64.
Van Eldere, J., Celis, P., De Pauw, G., Lesaffre, E., & Eyssen, H. (1996). Tauroconjugation of cholic acid stimulates 7α-dehydroxylation by fecal bacteria. Applied and Environmental Microbiology, 62, 656–661.
Peschel, A. (2002). How do bacteria resist human antimicrobial peptides? Trends in Microbiology, 10, 179–186.
Taranto, M. P., Sesma, F., Ruiz Holgado, A. P., & Font de Valdez, G. (1997). Bile salt hydrolase plays a key role on cholesterol removal by Lactobacillus reuteri. Biotechnology Letters, 19, 845–847.
Taranto, M. P., Fernandez Murga, M. L., Lorca, G., & Font de Valdez, G. (2003). Bile salts and cholesterol induce changes in the lipid cell membrane of Lactobacillus reuteri. Journal of Applied Microbiology, 95, 86–91.
Boggs, J. M. (1987). Lipid intermolecular hydrogen bonding: influence on structural organization and membrane function. Biochimica et Biophysica Acta, 906, 353–404.
Noriega, L., Cuevas, I., Margolles, A., & de los Reyes-Gavilan, C. G. (2006). Deconjugation and bile salts hydrolase activity by Bifidobacterium strains with acquired resistance to bile. Int Dairy J, 16, 850–855.
Martoni, C., Bhathena, J., Jones, M. L., Urbanska, A. M., Chen, H., & Prakash, S. (2007). Investigation of microencapsulated BSH active Lactobacillus in the simulated human GI tract. J Biomed Biotechnol. art. no. 13684.
Kurdi, P., Tanaka, H., van Veen, H. W., Asano, K., Tomita, F., & Yokota, A. (2003). Cholic acid accumulation and its diminution by short-chain fatty acids in bifidobacteria. Microbiology, 149, 2031–2037.
Coleman, J. P., White, W. B., Lijewski, M., & Hylemon, P. B. (1988). Nucleotide sequence and regulation of a gene involved in bile acid 7α-dehydroxylation by Eubacterium sp. strain VPI 12708. Journal of Bacteriology, 170, 2070–2077.
Wells, J. E., & Hylemon, P. B. (2000). Identification and characterization of a bile acid 7α-dehydroxylation operon in Clostridium sp. strain TO-931, a highly active 7α-dehydroxylating strain isolated from human feces. Applied and Environmental Microbiology, 66, 1107–1113.
Madsen, V. A., Brown, V. R., Grimes, S. M., Poppe, C. H., Anderson, J. D., Davis, J. C., et al. (1976). Effect of inelastic coupling on 0+ analog transitions. Physical Review C, 13, 548–555.
Eyssen, H., & De Somer, P. (1963). The mode of action of antibiotics in stimulating growth of chicks. The Journal of Experimental Medicine, 117, 127–138.
De Somer, P., Eyssen, H., & Evard, E. (1963). In A. C. Frazer (Ed.), The influence of antibiotics on fecal fats in chickens. Biochemical problems of lipids (pp. 84–90). Amsterdam: Elsevier/North Holland.
Eyssen, H. (1973). Role of the gut microflora in metabolism of lipids and sterols. The Proceedings of the Nutrition Society, 32, 59–63.
Eyssen, H., & De Somer, P. (1963). Effect of antibiotics on growth and nutrients absorption of chicks. Poultry Science, 42, 1373.
Feighner, S. D., & Dashkevicz, M. P. (1987). Sub-therapeutic levels of antibiotics in poultry feeds and their effects on weight gain, feed efficiency, and bacterial cholyltaurine hydrolase activity. Applied and Environmental Microbiology, 53(2), 331–336.
Feighner, S. D., & Dashkevicz, M. P. (1988). Effect of dietary carbohydrates on bacterial cholyltaurine hydrolase in poultry intestinal homogenates. Applied and Environmental Microbiology, 54(2), 337–342.
Fuller, R., Cole, C. B., & Coates, M. E. (1984). The role of Streptococcus faecium in antibiotic-relieved growth depression of chickens. British Poultry Science, 395–403.
Ridlon, J. M., Kang, D. J., & Hylemon, P. B. (2006). Bile salt bio-transformations by human intestinal bacteria. Journal of Lipid Research, 47, 241–259.
Bernstein, C., Bernstein, H., Payne, C. M., Dvorakova, K., & Garewal, H. (2005). Bile acids as carcinogens in human gastrointestinal cancers. Mutation Research, 589, 47–65.
Pazzi, P., Puriani, A. C., Dalla Libera, M., Guerra, G., Rici, D., Gullini, S., et al. (1997). Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in vitro study in perfused rat hepatocytes. European Journal of Gastroenterology & Hepatology, 9, 703–709.
Berr, F., Kullak-Ublick, G. A., Paumgartner, G., Munzing, W., & Hylemon, P. B. (1996). 7α-Dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones. Gastroenterology, 111, 1611–1620.
Mamianett, A., Garrido, D., Carducci, C. N., & Vescina, M. C. (1999). Fecal bile acid excretion pattern profile in gallstone patients. Medicina, 59, 269–273.
Masuda, N. (1981). Deconjugation of bile salts by Bacteroids and Clostridium. Microbiology and Immunology, 25(1), 1–11.
Lepercq, P., Relano, P., Cayuela, C., & Juste, C. (2004). Bifidobacterium animalis strain DN-173010 hydrolyses bile salt in the gastrointestinal tract of pigs. Scandinavian Journal of Gastroenterology, 39(12), 1266–1271.
Corzo, G., & Gilliland, S. E. (1999). Bile salt hydrolase activity of three strains of Lactobacillus acidophilus. Journal of Dairy Science, 82(3), 472–480.
Zoumpopoulou, G., Foligne, B., Christodoulou, K., Grangette, C., Pot, B., & Tsakalidou, E. (2008). Lactobacillus fermentum ACA-DC 179 displays probiotic potential in vitro and protects against sulfonic acid (TNBS)-induced colitis and Salmonella infection in murine models. International Journal of Food Microbiology, 121(1), 18–26.
Delpino, M. V., Marchesini, M. I., Estein, S. M., Comerci, D. J., Cassataro, J., Fossati, C. A., et al. (2007). A bile salt hydrolase of Brucella abortus contributes to the establishment of a successful infection through the oral route in mice. Infection and Immunity, 75, 299–305.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Patel, A.K., Singhania, R.R., Pandey, A. et al. Probiotic Bile Salt Hydrolase: Current Developments and Perspectives. Appl Biochem Biotechnol 162, 166–180 (2010). https://doi.org/10.1007/s12010-009-8738-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12010-009-8738-1