Lactobacillusspecies constitute a significant component of the human and animal microbiota at a number of body sites, such as the digestive system, and the female genital system.[4] In women of European ancestry, Lactobacillus species are normally a major part of the vaginal microbiota.[5][6]Lactobacillus forms biofilms in the vaginal and gut microbiota,[7] allowing them to persist during harsh environmental conditions and maintain ample populations.[8]Lactobacillus exhibits a mutualistic relationship with the human body, as it protects the host against potential invasions by pathogens, and in turn, the host provides a source of nutrients.[9] Lactobacilli are among the most common probiotic found in food such as yogurt, and it is diverse in its application to maintain human well-being, as it can help treat diarrhea, vaginal infections, and skin disorders such as eczema.[10]
Lactobacilli are homofermentative, i.e. hexoses are metabolised by glycolysis to lactate as major end product, or heterofermentative, i.e. hexoses are metabolised by the Phosphoketolase pathway to lactate, CO2 and acetate or ethanol as major end products.[11] Most lactobacilli are aerotolerant and some species respire if heme and menaquinone are present in the growth medium.[11] Aerotolerance of lactobacilli is manganese-dependent and has been explored (and explained) in Lactiplantibacillus plantarum (previously Lactobacillus plantarum).[12] Lactobacilli generally do not require iron for growth.[13]
The Lactobacillaceae are the only family of the lactic acid bacteria (LAB) that includes homofermentative and heterofermentative organisms; in the Lactobacillaceae, homofermentative or heterofermentative metabolism is shared by all strains of a genus.[3][11]Lactobacillus species are all homofermentative, do not express pyruvate formate lyase, and most species do not ferment pentoses.[3][11] In L. crispatus, pentose metabolism is strain specific and acquired by lateral gene transfer.[14]
Genomes
The genomes of lactobacilli are highly variable, ranging in size from 1.2 to 4.9 Mb (megabases).[3] Accordingly, the number of protein-coding genes ranges from 1,267 to about 4,758 genes (in Fructilactobacillus sanfranciscensis and Lentilactobacillus parakefiri, respectively).[15][16] Even within a single species there can be substantial variation. For instance, strains of L. crispatus have genome sizes ranging from 1.83 to 2.7 Mb, or 1,839 to 2,688 open reading frames.[17]Lactobacillus contains a wealth of compound microsatellites in the coding region of the genome, which are imperfect and have variant motifs.[18] Many lactobacilli also contain multiple plasmids. A recent study has revealed that plasmids encode the genes which are required for adaptation of lactobacilli to the given environment.[19]
Species
The genus Lactobacillus comprises the following species:[20][21]
Homofermentative, aerotolerant and vancomycin resistant. Genome size, G+C content of the genome and the source of the two species suggest a free-living lifestyle of the genus.
Homofermentative, vancomycin resistant, aerotolerant. Schleiferilactobacillus spp. have a large genome size, ferment a wide range of carbohydrates, and spoil beer and dairy products by copious production of diacetyl.
Homofermentative, vancomycin resistant; many species ferment pentoses, and are resistant to oxidative stress. L. casei and related species have a nomadic lifestyle.
Homofermentative, vancomycin resistant, motile organisms growing in liquid, plant-associated habitats. Many liquorilactobacilli produce EPS from sucrose and degrade fructans with extracellular fructanases.
Homofermentative, vancomycin resistant, most ligilactobacilli are host adapted and many strains are motile. Several strains of Ligilactobacillus express urease to withstand gastric acidity.
Homofermentative, vancomycin resistant organisms with a nomadic lifestyle that ferment a wide range of carbohydrates; most species metabolise phenolic acids by esterase, decarboxylase and reductase activities. L. plantarum expresses pseudocatalase and nitrate reductase activities.
Heterofermentative, thermophilic, vancomycin resistant with two exceptions, Limosilactobacillus species are vertebrate host adapted and generally form exopolysaccharides from sucrose to support biofilm formation in the upper intestine of animals.
Heterofermentative, vancomycin resistant, mesophilic, aerotolerant, small genome size. Fructilactobacilli are adapted to narrow ecological niches that relate to insects, flowers, or both.
Heterofermentative, vancomycin resistant, mesophilic or psychrotrophic, environmental or plant-associated lifestyle. Adapted to hexose-depleted habitats, most strains do not reduce fructose to mannitol but metabolize agmatine and diols.
Heterofermentative, vancomycin resistant, mesophilic, fermenting a broad spectrum of carbohydrates. Most lentilactobacilli are environmental or plant-associated, metabolise agmatine and convert lactate and/or diols. L. senioris and L. kribbianus form an outgroup to the genus; both species were isolated from vertrebrates and may transition to a host-adapted lifestyle.
Lactobacilluss.s. species are considered "keystone species" in the vaginal flora of reproductive-age women.[23] Most, but not all, healthy women have vaginal floras dominated by one of four species of Lactobacillus: L. iners, L. crispatus, L. gasseri and L. jensenii. Other women have a more diverse mix of anaerobic microorganisms, though are still considered to have a healthy microbiome.[5]
Interactions with pathogens
Lactobacilli produce lactic acid, which contributes to the vaginal acidity, and this lowered pH is generally accepted to be the main mechanism controlling the composition of the vaginal microflora.[24]
In vitro studies have also shown that lactobacilli reduce the pathogenicity of C. albicans through the production of organic acids and certain metabolites.[28] Both the presence of metabolites, such as sodium butyrate, and the decrease in environmental pH caused by the organic acids reduce the growth of hyphae in C. albicans, which reduces its pathogenicity.[28] Lactobacilli also reduce the pathogenicity of C. albicans by reducing C. albicans biofilm formation.[28] Biofilm formation is reduced by both the competition from lactobacilli, and the formation of defective biofilms which is linked to the reduced hypha growth mentioned earlier.[28] On the other hand, following antibiotic therapy, certain Candida species can suppress the regrowth of lactobacilli at body sites where they cohabitate, such as in the gastrointestinal tract.[25][26]
In addition to its effects on C. albicans, Lactobacillus sp. also interact with other pathogens. For example, Limosilactobacillus reuteri (formerly Lactobacillus reuteri) can inhibit the growth of many different bacterial species by using glycerol to produce the antimicrobial substance called reuterin.[29] Another example is Ligilactobacillus salivarius (formerly Lactobacillus salivarius), which interacts with many pathogens through the production of salivaricin B, a bacteriocin.[30]
Probiotics
Because of the interactions with other microbes, fermenting bacteria like lactic acid bacteria (LAB) are now in use as probiotics with many applications.
Lactobacilli administered in combination with other probiotics benefits cases of irritable bowel syndrome (IBS), although the extent of efficacy is still uncertain.[31] The probiotics help treat IBS by returning homeostasis when the gut microbiota experiences unusually high levels of opportunistic bacteria.[9] In addition, lactobacilli can be administered as probiotics during cases of infection by the ulcer-causing bacterium Helicobacter pylori.[32]Helicobacter pylori is linked to cancer, and antibiotic resistance impedes the success of current antibiotic-based eradication treatments.[32] When probiotic lactobacilli are administered along with the treatment as an adjuvant, its efficacy is substantially increased and side effects may be lessened.[32] In addition, lactobacilli with other probiotic[33] organisms in ripened milk and yogurt aid development of immunity in the mucous intestine in humans by raising the number of LgA (+).
Given the known microbial associations, lactobacilli are currently available as probiotics to help control urogenital and vaginal infections, such as bacterial vaginosis (BV). Lactobacilli produce bacteriocins to suppress pathogenic growth of certain bacteria,[35] as well as lactic acid, which lowers the vaginal pH to around 4.5 or less, hampering the survival of other bacteria.
In children, lactobacilli such as Lacticaseibacillus rhamnosus (previously L. rhamnosus) are associated with a reduction of atopic eczema, also known as dermatitis, due to anti-inflammatory cytokines secreted by this probiotic bacteria.[9]
Oral health
Some lactobacilli have been associated with cases of dental caries (cavities). Lactic acid can corrode teeth, and the Lactobacillus count in saliva has been used as a "caries test" for many years. Lactobacilli characteristically cause existing carious lesions to progress, especially those in coronal caries. The issue is, however, complex, as recent studies show probiotics can allow beneficial lactobacilli to populate sites on teeth, preventing streptococcal pathogens from taking hold and inducing dental decay. The scientific research of lactobacilli in relation to oral health is a new field and only a few studies and results have been published.[36][37] Some studies have provided evidence of certain Lactobacilli which can be a probiotic for oral health.[38] Some species, but not all, show evidence in defense to dental caries.[38] Due to these studies, there have been applications of incorporating such probiotics in chewing gum and lozenges.[38] There is also evidence of certain Lactobacilli that are beneficial in the defense of periodontal disease such as gingivitis and periodontitis.[38]
Their importance in fermentation comes from both metabolism of the food itself, as well as the inhibition of growth of other potentially pathogenic microbes. The antibacterial and antifungal activity of lactobacilli relies on production of bacteriocins and low molecular weight compounds that inhibits these microorganisms.[41][42]
Sourdough bread is made either spontaneously, by taking advantage of the bacteria naturally present in flour, or by using a "starter culture", which is a symbiotic culture of yeast and lactic acid bacteria growing in a water and flourmedium.[43] The bacteria metabolize sugars into lactic acid, which lowers the pH of their environment and creates the signature sourness associated with yogurt, sauerkraut, etc.
In many traditional pickling processes, vegetables are submerged in brine, and salt-tolerant lactobacilli feed on natural sugars found in the vegetables. The resulting mix of salt and lactic acid is a hostile environment for other microbes, such as fungi, and the vegetables are thus preserved—remaining edible for long periods.[44]
Lactobacilli, especially pediococci and L. brevis, are some of the most common beer spoilage organisms. They are, however, essential to the production of sour beers such as Belgian lambics and American wild ales, giving the beer a distinct tart flavor.[45]
Scientist Elie Metchnikoff won a Nobel prize in 1908 for his work on LAB, the connection to food, and possible usage as a probiotic.[46]
^Inglin R (2017). Combined Phenotypic-Genotypic Analyses of the Genus Lactobacillus and Selection of Cultures for Biopreservation of Fermented Food. ETHZ research collection (Ph.D. thesis). ETH Zurich. doi:10.3929/ethz-b-000214904. hdl:20.500.11850/214904.
^Basharat Z, Yasmin A (December 2015). "Survey of compound microsatellites in multiple Lactobacillus genomes". Canadian Journal of Microbiology. 61 (12): 898–902. doi:10.1139/cjm-2015-0136. hdl:1807/69860. PMID26445296.
^ abWang ZK, Yang YS, Stefka AT, Sun G, Peng LH (April 2014). "Review article: fungal microbiota and digestive diseases". Alimentary Pharmacology & Therapeutics. 39 (8): 751–66. doi:10.1111/apt.12665. PMID24612332. S2CID22101484. In addition, GI fungal infection is reported even among those patients with normal immune status. Digestive system-related fungal infections may be induced by both commensal opportunistic fungi and exogenous pathogenic fungi. ... In vitro, bacterial hydrogen peroxide or organic acids can inhibit C. albicans growth and virulence61 In vivo, Lactobacillus sp. can inhibit the GI colonisation and infection of C. albicans62 In vivo, C. albicans can suppress Lactobacillus sp. regeneration in the GI tract after antibiotic therapy63, 64
^ abErdogan A, Rao SS (April 2015). "Small intestinal fungal overgrowth". Current Gastroenterology Reports. 17 (4): 16. doi:10.1007/s11894-015-0436-2. PMID25786900. S2CID3098136. Small intestinal fungal overgrowth (SIFO) is characterized by the presence of excessive number of fungal organisms in the small intestine associated with gastrointestinal (GI) symptoms. Candidiasis is known to cause GI symptoms particularly in immunocompromised patients or those receiving steroids or antibiotics. However, only recently, there is emerging literature that an overgrowth of fungus in the small intestine of non-immunocompromised subjects may cause unexplained GI symptoms. ... Fungal-bacterial interaction may act in different ways and may either be synergistic or antagonistic or symbiotic [29]. Some bacteria such as Lactobacillus species can interact and inhibit both the virulence and growth of Candida species in the gut by producing hydrogen peroxide [30]. Any damage to the mucosal barrier or disruption of GI microbiota with chemotherapy or antibiotic use, inflammatory processes, activation of immune molecules and disruption of epithelial repair may all cause fungal overgrowth [27].
^Brink, B. ten; Minekus, M.; van der Vossen, J.M.B.M.; Leer, R.J.; Huis in't Veld, J.H.J. (August 1994). "Antimicrobial activity of lactobacilli: preliminary characterization and optimization of production of acidocin B, a novel bacteriocin produced by Lactobacillus acidophilus M46". Journal of Applied Microbiology. 77 (2): 140–148. doi:10.1111/j.1365-2672.1994.tb03057.x. PMID7961186.
^Ford AC, Quigley EM, Lacy BE, Lembo AJ, Saito YA, Schiller LR, Soffer EE, Spiegel BM, Moayyedi P (October 2014). "Efficacy of prebiotics, probiotics, and synbiotics in irritable bowel syndrome and chronic idiopathic constipation: systematic review and meta-analysis". The American Journal of Gastroenterology. 109 (10): 1547–61, quiz 1546, 1562. doi:10.1038/ajg.2014.202. PMID25070051. S2CID205100508.
^Twetman S, Stecksén-Blicks C (January 2008). "Probiotics and oral health effects in children". International Journal of Paediatric Dentistry. 18 (1): 3–10. doi:10.1111/j.1365-263X.2007.00885.x. PMID18086020.
^Inglin RC, Stevens MJ, Meile L, Lacroix C, Meile L (July 2015). "High-throughput screening assays for antibacterial and antifungal activities of Lactobacillus species". Journal of Microbiological Methods. 114 (July 2015): 26–9. doi:10.1016/j.mimet.2015.04.011. PMID25937247.
^Inglin, Raffael (2017). PhD Thesis - Combined Phenotypic-Genotypic Analyses of the Genus Lactobacillus and Selection of Cultures for Biopreservation of Fermented Food (Doctoral Thesis). ETH Zurich. doi:10.3929/ethz-b-000214904. hdl:20.500.11850/214904.