Lactobacillus Species as Probiotics: Isolation Sources and Health Benefits

Recently, the attention to exploring and applying probiotics has been increased. Probiotics are living microscopic organisms that have valuable impacts on health when consumed in adequate amounts. One of the most popular widespread utilized probiotics for many years until now is the Lactobacillus species which exemplifies the hugest heterogeneous group among the lactic acid bacteria (lAB) that normally occupy many environments that contain high nutrient levels such as soil, humans, waters, plants, animals and even air without causing any illness. the purpose of this work is to review and demonstrate the wide diversity of lactobacilli isolation sources and related health benefits applications of the strains discovered in order to break the familiar sources of lactobacillus spp., thereby encouraging more research into unconventional sources and opening up opportunities for clinical applications of Lactobacillus spp. As a result, the isolation sources of lactobacillus spp. in this review have been split into two groups based on the environmental condition, including fermented and non-fermented habitats described as lactobacilli probiotic sources. the unique lactobacilli isolated from various sources are regarded as potential therapies for a variety of illnesses and physiological abnormalities, including immunomodulation, suppression of carcinogenesis, and cholesterol reduction, in addition to their capacity to guard against infections. this will be highly significant for revealing updated information about Lactobacillus spp. that has attracted considerable attention due to its potential application in clinical practices.

of the most popular and widely used probiotics for many years until now which exemplifies the hugest heterogeneous group among LAB. 18actobacilli are members of LAB, a diversified group of catalase-negative, Grampositive, non-spore-forming and anaerobic or aero tolerant, coccobacilli, or rod-shaped that is mainly characterized by the lactic acid production as the main end product of their carbohydrate fermentation. 19actobacilli occupy many nutrient-rich habitats and environments such as spoiled and fermented food and are found in animal feed, soil, and body of invertebrate and vertebrate animals. 20hey live naturally in our body by inhabiting the digestive tract, oral cavity, genital and urinary system. 21Members of the Lactobacilli group have been generally renowned as safe (GRAS) by Food and Drug Administration (FDA) due to their frequent abundance in our food like cheese and yogurt without causing illnesses. 22actobacillus genus characterized by a massive genome possesses a high grade of genetic diversity and physiology which make them a targeted candidate in many important applications, such as the production of fermented food, food bio preservation strategies to prolong the shelf life while guaranteeing their safety, and in health improvement applications. 23,24he reason behind the focus on Lactobacillus is due to their vast impact on the host immune system, considered safe in use, show a competitive exclusion, and own a high adhering ability. 25This work is aimed to review the wide variety of lactobacilli isolation sources and associated health benefits applications of the strains discovered to break the acquainted sources of lactobacillus spp., thus also inspiring more research to isolate new strains from unconventional sources and providing possibilities for more clinical applications.

taxonomy of Lactobacilli
Lactobacilli were one of the earliest classified bacteria due to their ubiquitous existence in many fermented products.Numerous classifications have been improved since the first description of the Lactobacillus genus by Beijerink in 1901. 26he base of the initial taxonomy of lactobacilli was depend on the observable and measurable traits including cell morphology, gram stain, colony appearance, optimum growth temperature, pH tolerance, oxygen requirements, and pathways for carbohydrate fermentation which classified lactobacilli according to the type of fermented sugars and fermentation products into three general groups; obligate homofermentative, facultative heterofermentative and obligate heterofermentative. 27,28n the 1980s, with the entrance of bacterial taxonomy the genetic age, genotypic and chemotaxonomic characteristics were used in classification.The availability of 16S rRNA sequencing allowed the first phylogenetic analysis of the Lactobacillus which uncovered an extensive diversity by the generation of a true phylogenetic tree that contributed to the development of the taxonomy of lactobacilli. 27,28After the evolution of molecular techniques, most species have been named again and some reclassified to other genera.
The Lactobacillus genus implicates more than 200 species distinguished by phylogenetic and metabolic diversity.About 540 species and 54 subspecies of this genus have been identified according to the online database of List of Prokaryotic names with standing in Nomenclature (LPSN) (http://www.bacterio.net/lactobacillus.html) which is classified by the taxonomy requirements of the International Code of Nomenclature of Prokaryotes such as L. achengensis. 19,20,29olation Sources of Lactobacillus spp.

Biological Sources Fermented Biological Sources
Lactobacillus spp.are food spoilage organisms that control the vast majority of the microbiota of fermented foods. 30,31Fermented vegetables, silage, also various grains rely on the basic material type as an inoculum source.Other fermented sources such as the majority of dairy fermentations, fermented meats, and sourdough, are produced by the manufactured environments of diverse lactic acid bacteria isolated from natural sources. 32,33Microorganisms in fermented products are subjected to centuries of growing continuously, becoming accustomed to the fermented product. 34,35 s a consequence of lactobacillus' capacity to adapt to multiple conditions in different environments, lactobacilli isolation may be inoculated into many different types of goods or natural environments in order to produce novel strains and, as a result, prospective therapeutic uses.
Traditional fermented foods have recently been investigated as potential natural probiotic bacteria sources, according to recent studies.The Lactobacillus genus is home to the bulk of microorganisms isolated from fermented environments. 36The Genus of Weissella was obtained from traditional food under fermentation conditions in Nigeria followed by an evaluation of potential probiotics abilities in a recent investigation. 37actobacillus delbrueckii subsp.bulgaricus appears to be adapting to conditions in fermented products, as evidenced by a rapid and continuing decrease in the size of the genome. 37As a result, despite the fact that the vast majority of the strain types were obtained from fermented foods, they are improbable to serve as Lactobacillus' main habitat.Lactobacillus species can be isolated directly from a variety of natural and man-made fermented environments and products:

dairy Products
Probiotics are used in a variety of dairy products, including sour/fermented milk, cheese, yogurt, butter/cream, new-born formula, and ice cream, according to the dairy industry.Probiotics are also utilized as starting cultures in conventional starters, either alone or in combination, or integrated into dairy products after fermentation, where their presence adds many functional characteristics to the fermented product (for example, improved taste, aroma, and textural characteristics), as well as conferring many healthpromoting effects. 38he fermented milk includes multiplex species of LAB and hence serve as an excellent probiotic supply.It should come as no surprise that Streptococcus thermophilus and L. delbrueckii subsp bulgaricus are the most prevalent microbiological communities were found recently in the fermented yak milk (Kurut). 39Furthermore, probiotic lactobacillus strains and yeasts were identified from kefir grains, Koumissm, a fermented milk drink; and Masai milk; these bacteria have the capacity to favorably alter immunological responses. 40,41ome products, such as yogurt, cheese, and butter, can benefit from the addition of starting cultures made from milk or milk alone.In comparison to the traditional Luria-Bertani medium, milk whey, a dairy by-product from the cheese manufacturing industry, is utilized to develop LAB to create more lactic acid.As a result, it might be one of several sources from which advantageous LAB strains can be obtained 42 (Figure 1).

Meats
LAB strains used to be detected in a variety of traditional fermented foods, such as beef, 43 fish, 44 pork, 45 and seafood. 46Enterococcus is the most common LAB strain recovered from fermented crustaceans and fishes, whereas Lactobacillus is the most common LAB obtained from fermented meats and plants. 47,48Due to the complex components of meats, LAB extracted from such environments is likely to be more diversified functionally and physiologically and it is likely to provide further therapeutic applications than LAB isolated from other sources (Figure 1).

Grains, Fruits & Vegetables
Lactobacilli strains from Plant-derived LAB are the most halophilic and flourished at NaCl concentrations greater than 22%.Significance species of lactobacillus were collected from fermentation condition of the plant parts are L. plantarum and L. fermentum.In addition, the various basic substance of dry wheats, garlic, olives, as well as parsley used in fermented food are high in LAB and may be tested for probiotic strains. 45actobacilli isolated from the natural brine of Algren, green olive fermented, was discovered in recent research. 48Several health benefits can be obtained from L. buchneri P2 as a potential probiotic collected from pickle juice was proved to have properties of antimicrobial activity, cholesterol reduction, and tolerance to acid and bile juice. 49actobacillus spp. or Leuconostoc spp.Were represented the majority of LAB isolated in a study from sauerkraut fermentations and investigated to discover their probiotic properties and determined genotypic and phenotypic characterization of the isolates were found in four different sauerkraut fermentations 50 (Figure 1).
LAB isolated from manufactured fermented products that basically contain plant parts are generated due to the contamination conditions during production processes or from endophytes bacteria.Endophytes lactobacillus spp.recovered from plant parts have the capacity to survive in a wide variety of PH gradients, allowing LAB to be separated from mild PH conditions of plant tissues or surfaces.lactobacilli did, however, exhibit a definite preference for improved development in a low pH environment.

traditional Food & Beverages
Many of the isolated species of Traditional fermented foods and drinks flourished in NaCl concentrations of less than 6%. 51Traditional Thai salted crab also contains NaCl-like LAB (Poo-Khem).The fish dressing is identified as meal prepared under fermentation condition created from various basic ingredients including fish and shellfish.Probiotic isolates of L. plantarum was isolated from fermented soybean, popular traditional food in India, in addition, other genera of LAB including Lactobacillus, Vagococcus, Weissella, and Enterococcus were discovered. 52fter conducting several tests to determine LAB genera isolated from natural fermented dry sausage, L. plantarum and, L. brevis have been identified as the crucial lactobacillus spp. 53The majority of L. plantarum isolates from LAB came from traditional fermented Turkish beverages (Boza).To overcome Bacteria that cause disease including B. subtilis, B. cereus, E. coli, P. aeruginosa, L. monocytogenes, and K. pneumoniae, the antagonistic activity of isolates was exanimated by produced substances (primarily hydrogen peroxide and organic acids). 54In addition, various studies reported that probiotic LAB was collected from ungerminated cereal crops mixed with millet cereals known as (Kunu-zaki) as a traditional fermented beverage in Nigeria 55 (Figure 1).
Lactobacilli utilized in traditional meals are either mesophilic or thermophilic, depending on the kind of ingredients and preparation circumstances, and may live at low temperatures as Psychrophilic bacteria.Lactobacillus spp.thrive in a wide range of temperatures, putting them at the forefront of bacterial species found in traditional meals.

Waste & Sewage
L. delbrueckii is one of the other species of lactobacillus that can be obtained from Fermented veggies that were discarded and inhibited the development of various harmful bacteria such as E. coli, P. aeruginosa and P. vulgaris. 56actobacilli can be discovered in sewage due to fecal contamination. 57potential probiotics had been located in diffusion of areas of the human body, consisting of human feces remoted from each healthful adult and youngsters 58 and breast-fed newborns 59 (Figure 1).
Lactobacilli found in waste or sewage come from a variety of original environments, including humans, animals, and plants.Because of the abundance of complex components and the availability of growth nutrients, waste circumstances enable optimal development for Lactobacillus spp.

From Non-fermented Biological Sources traditional Food & Beverages
In numerous traditional non-fermented drinks have an excessive number of probiotics.Non-fermented drinks are created from a range of ingredients, including grains, millets, fruits, legumes, and vegetables. 60hese meals and beverages are mostly composed of fresh items infected with lactobacillus spp., such as "waldorf" salad 61 (Figure 1).

Grains, Fruits & Vegetables
Microorganisms containing Probiotic properties may be isolated from raw materials of plant origin including fruits and their liquids, 62 honeycomb, 63 cereals, 64 and dirt. 65,66L. plantarum specifically and many other LAB strains were isolated in a study from different kind of fruit juices, whereases L. mesenteroides is seldom isolated from fruits, however, it has been found in tomato. 62Another growing medium may be utilized to produce LAB and isolate lactobacilli from origin including pineapple waste and tomato juice. 67,68Lactobacillus kunkeei is one of the most common strains from the majority of Lactobacillus spp.among LAB.These species have been shown to have antibacterial properties against yeast development as well as spoilage-related effects in honey by yeast. 69Several studies have indicated that fruit juice, vegetables, and long grass may be used to isolate LAB. Green olives were used to isolate L. plantarum, L. pentosus, and L. paracasei, whereas L. mesenteroides and L. pentosus were isolated from dark olives. 70,71everal characteristics were examined to identify the probiotic potential of specific strains after isolation in a propitiate nutrient media of LAB.Plants Sources like papaya, yam, cassava, sugarcane, and taro leaves were confirmed to contain isolates of lactobacillus spp.by reading the sequence of 16S rDNA of the samples, species were recognized as L. paraplantarum and L. plantarum isolated from crops leaves. 72ccording to one study, these LAB isolated from plant sources may not be present in the regular microflora of plants grown recently, Lactobacillus spp.can be isolated from dead plants or raw materials such as olives, cabbage, carrots, beets, and fruits (for example pears and grapes). 73owever, identification of lactobacillus spp.from surfaces of flowers or in the tissues of the other plant parts is restricted. 74,75he leaves of P. aquilinum and, Aloe Barbadensis, also seeds of L. usitatissimum, roots of D. carota, and flowers of P. cerasifera were investigated, and 14 distinct LAB were identified as Lactococcus and Lactobacillus, as well as 8 various enterococci.species were initially identified by API kit, and then again analyzed given information by PCR technology, which corroborated the biochemical outcomes.The strains of LAB were isolated from plants' parts comprised of Lactobacillus delbrueckii subsp.Bulgaricus, Lactobacillus brevis, Lactococcus lactis, Lactobacillus acidophilus, and some species of Leuconostoc 76 (Figure 1).
The epiphyte Lactobacillus spp.outnumbered the endophyte bacteria, the reason may back to the species coming from surrounding sources such as animals, humans, waste, and soil.Climate, geographical factors, plant type, resident microbial communities, and Physical factors of the environment can impact lactobacilli dispersion in plants.

Vertebrate & Invertebrate
Animal intestines, according to Siddiqee et al., are the most likely source of LAB. 77Several probiotic strains have been identified from human sources, including human breast milk, from various regions of the human body. 78he non-sterile breast milk, even if amassed aseptically, still makes the chance of containing isolates of lactobacillus spp. in high odds.79 Breast milk bacteria were long thought to be the result of cutaneous or fecal infections.Although genotypes of lactobacillus spp. in breast milk differ from the genes of the isolates lactobacilli collected from the skin, 80 also the strains of LAB detected in breast milk also were discovered inside newborns' excrement.78 Lactobacillus spp.can be found in numerous amounts in breast milk as a natural source of probiotics to be for incorporation into food products. 74Lactobacillus species are among the most common bacteria isolated from breast milk, 81 also its consumption promotes the predominance of one more source of probiotics in the human intestinal tract.over 500 various species of bacteria can be obtained from the stomach of adult humans Indeed, many of today's probiotic strains, including L. gasseri and L. reuteri, were isolated from this source.82 It's a common misconception that the digestive tract should be the sole residence for the probiotics strains to be more beneficial.83 Probiotics are present in the stomachs of many animals, including rats, pigs, and even chickens.84 Lately, strains of Lactobacillus johnsonii, collected from Apis mellifera stomach, were proven to boost honeybee colonies.85 Probiotics' isolates were also identified from the digestive tract of freshwater and marine fish, including Carassius auratus gibelio, 86 rainbow trout, 87 and shrimp.88 In vitro research has shown that some strains of bacteria obtained from meats (lactobacillus sakei, Staphylococcus carnosus, and lactobacillus curvatus) and fruits (L.plantarum and L. paracasei) exhibit functional and metabolic features comparable to bacteria of adult's intestine.89 Lactobacilli may be isolated consistently from a broad variety of insects, including bees and flies, as well as vertebrates such as rodents, birds, people, and agricultural animals.][91][92]  tend to favor food storage organs in animal hosts, such as the crop and forestomach.Insects including bees, flies, bumblebees, and vertebrates' organs were used to isolate lactobacillus species.digestive tract, mouth cavity, vagina, and saliva and feces of healthy adults can be considered as non-fermented sources of lactobacillus isolates. 93Tajabadi et al. extracted LAB from honey collected from massive honeybees.94 Lactic Acid Bacteria (LAB) from ten healthy wild giant freshwater prawns' stomachs and hepatopancreas, Macrobrachium rosenbergii, were identified in a recent study to investigate native probiotic strains for additional uses.According to the findings, two LAB isolates, L. plantarum and E. faecalis, have been recommended as prospective Probiotics derived from huge freshwater prawns to enhance the aquaculture sector 95 (Figure 1).
The presence of Lactobacillus spp.species in many terrestrial and marine organisms gives a clear indication of the concept of one health approach.Therefore, the balance of these species in other organisms and environments can provide solutions for environmental balance, food security, and public health alike.

environmental Sources
Environments around food products, for example, have also been isolated as unconventional sources of high potential probiotics.

Air
The air in the surrounding environs, as well as the air in a bakery's storage and working rooms, can be a source of lactobacilli during the sourdough preparation process.L. plantarum was discovered in the samples, which is comparable to the one collected from the dough.in addition, Lactobacilli were isolated from the air around palm plants 56,96 (Figure 1).

Soils
Probiotic bacteria isolated from soil in Japan and Taiwan have been discovered and categorized.In order to isolate LAB in Japan and Taiwan, 68 soil samples were collected from various animal areas including the area surrounding the horse farm and floors of the henhouses.Several tests were conducted Physiologically and genetically to determine strains of LAB.54 out of 68 isolates identified as LAB.This clearly indicates the existence of LAB in significant numbers.According to the findings, dirt may be a frequent source of lactic acid bacteria isolation.
The initial habitat of many isolates came from soil sources.These lactobacillus isolates can be transferred to any product or habitat derived from the rhizosphere or phyllosphere of plants 57,74,97 (Figure 1).

Aquatic environments
In aquatic environments, scientists are interested in isolates from the gastrointestinal tract of marine organisms.Lactobacillus spp.Were collected from the GIT of several fish and shrimp.However, the environment surrounding and hydro planktons that form as nutrients for the marine organisms are rich in probiotic strains (Figure 1).

the Significant Roles of lactobacillus Species in Our life
Human has very tight contact with an enormous number of microorganisms that exist in the mouth, skin, or in gut.Some of them possess remarkable health functions such as inducing the immune system, owning an agnostic activity against invading pathogens, enhancing the digestion process, and amending many diseases. 98here are many identified Lactobacillus species that have been reported as probiotics and have beneficial effects on health (Figure 2).

Protection against Pathogens
Inhibiting the growth of pathogens is one of the ways probiotics benefit human health.These probiotics compete for resources that pathogens would use for growth and proliferation.As a result, they provide protection against pathogens colonization by causing direct death and competing for resources. 99

In the Gastrointestinal tract
Probiotics are one of the most effective ways to influence human health and disease by balancing the gut flora. 100everal studies demonstrated the role of Lactobacillus as a probiotic against many pathogens such as Lactobacillus acidophilus is safe for human epithelial colorectal cells and efficacious enough to be utilized as a supplementary treatment for reducing toxin generation in Vibrio cholerae and Shigella dysenteriae caused acute infectious diarrhea. 101urthermore, it was reported that taking Lactobacillus rhamnosus HN001 on a regular basis lowered the risk of Staphylococcus aureus carriage in the human gastrointestinal tract (GI).Competitive inhibition is the key possible mechanism of L. rhamnosus HN001, in which pathogen colonization is limited by beneficial commensal microbes out-competing them for vital resources in the GI tract. 102n another study, Jun Meng and others found that the surface layer protein (SLP) of Lactobacillus casei fb05 might reduce Escherichia coli and Salmonella's harmful effects on the digestive tract in two ways: by lowering pathogen adherence and avoiding apoptosis caused by pathogens. 103he leading cause of disruption of the normally protective gastrointestinal microbiota is Clostridium difficile infection (CDI) and antibiotic usage is a common cause of this condition.However, the supplementation of a certain probiotic combining Lactobacillus casei, L. rhamnosus, and L. acidophilus strains has been shown to be effective in inhibiting a number of undesirable consequences., including CDI and antibiotic-associated diarrhoea. 104The information about the gut microbiome is constantly accumulating which has heightened the interest in gut microbiome-based healthcare (Figure 3).
Because of the strong connections between gut microbiota, health, and disease, there is a lot of interest in utilizing probiotics to alter the gut microbiota in order to treat or prevent certain diseases.However, more research is required to ascertain which probiotic species and strains, dosage, and duration of treatment are efficient.It is also necessary to look into any potential probiotic-diet interactions and interindividual variability that may result in disparate responses to probiotics.

In the Vaginal tract
There are a variety of normal mycobiota and microbiota that colonize the human vagina, but Lactobacillus is the most prevalent bacteria found in the normal vaginal tract.These vaginal lactobacilli have been claimed as having the ability to prevent disease invasion by controlling their population. 105actobacillus has been shown to have fundamental probiotic effects against infections in the vaginal tract in several investigations.Fermentation of Lactobacillus acidophilus KS400 has been shown to generate bacteriocin that prevents urogenital pathogens growth like G. vaginalis, S. agalactiae, and P. aeruginosa. 106n addition, Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001exhibit antibacterial activities against several pathogens that were responsible for aerobic vaginosis (Staphylococcus aureus and Escherichia coli) and bacterial vaginosis (Atopobium vaginae and Gardnerella vaginalis) by means of a co-culturing assay. 107he L. Plantarum new isolates called ZX1, ZX2, ZX27, and ZX69 were found to limit Gardnerella vaginalis growth, the Bacterial vaginosis causative agent. 108n another study, they demonstrated that the major Lactobacillus species linked to a healthy vagina is L. crispatus may effectively block the growth of C. Albicans and the formation of hyphae.In an NRG1-dependent way, L. crispatus may also suppress the hyphae-specific gene expression (ALS3, HWP1, and ECE1).Furthermore, L. crispatus B145 is an excellent candidate for probiotic research. 109lso, a Lactobacilli dominated vaginal ecology has the ability to protect the host from human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). 110,111. crispatus BC3 and L. gasseri BC12 protect isolated cells and ex vivo tissues from infection with the Human Immunodeficiency Virus 1 (HIV-1) by releasing their extracellular vehicles (EVs) this finding could lead to new HIV-1 prevention measures for male-to-female sexual transmission 112 (Figure 3).
Moreover, Lactobacillus shows to be a promising influence to use in the prevention of vaginal infections such as vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV). 105o reduce the need for antimicrobial medications, a complementary method involving Lactobacillus to correct the imbalance of vaginal microbiota is urgently needed.To treat the heterogeneity of probiotic effectiveness, there should be more scientific investigations on the effectiveness of probiotic lactobacilli against vaginal infection.

In Skin Health
The skin is one of the largest organs in the human body, and it serves as a vital barrier and protective barrier against pathogen invasion. 113or many years, various studies on Lactobacillus and skin health have been published, including prevention of skin illness and improvement of skin diseases.
Several studies have shown that exogenously applied lactobacilli, for example Lactobacillus rhamnosus GG and Lactobacillus reuteri DSM 17938 have been found to have antipathogenic properties both directly and indirectly.Lactobacilli or their lysates, through direct binding interactions, can prevent infections from adhering to keratinocytes or actively displace adherent pathogens, as proven in vitro against S. aureus.][116] Furthermore, live L. reuteri DSM 17938 demonstrated antibacterial activity against pathogens on the skin including (Streptococcus pyogenes M1 Staphylococcus aureus, Pseudomonas aeruginosa, and Cutibacterium acnes AS12). 116xopolysaccharides and the primary peptidoglycan hydrolase Msp1 were identified as important components of L. rhamnosus GG that reduced C. albicans hyphae production and attachment to host epithelial cells. 117nder the influence of Lactobacillus pentosus KCA1, L. rhamnosus GG, and L. plantarum WCFS1 has greatly reduced the lipase activity of Cutibacterium acnes that helps in the conversion of sebum into free fatty acids, contributing to acne (Figure 3).These mechanistic insights have already been converted into positive therapeutic outcomes in a few clinical trials, demonstrating that topically applied lactobacilli can colonize the skin for a short period of time and improve skin health, However, in order to generate in vivo mechanistic insights and in-depth skin microbiome analyses, more and larger clinical studies are required. 118,119umerous novel probiotic products are being developed for the treatment of various skin problems as a result of these studies on the gut and skin microbiomes, which have produced some extremely insightful findings.Additionally, Eczema, atopic dermatitis, acne, and allergic inflammation are just a few of the skin conditions that probiotic bacteriotherapy may help prevent and treat.It may also help reduce skin hypersensitivity and help protect against UV-induced skin damage and wounds.It can also be applied topically.

Combating Physiological disorders
L a c t o b a c i l l u s p r o b i o t i c s h a v e demonstrated effectiveness in a variety of clinical disorders and conditions ranging from diarrhea, female urogenital infection, Helicobacter pylori infections and inflammatory bowel disease to cancer 98,119 (Table ).
The impact of gut microbiota on host physiological regulation has recently gotten a lot of attention, especially in crucial areas including the immune system and metabolism. 153

Immunomodulation
The immunomodulatory activities of probiotics can act both directly and indirectly.Directly such as by increasing the activity of natural killer cells or macrophages modulating the secretion of cytokines or immunoglobulins.Indirectly by competitive exclusion of other (pathogenic) bacteria, enhancing the gut epithelial barrier and altering the mucus secretion. 154nti-commensal antibodies, innate cytokines, and Th17 responses were all reduced after oral gavage with L. reuteri, reducing immunological hyper-reactivity (Table ).Also, autochthonous Lactobacillus may also aid in the restoration of immunological homeostasis and the resolution of infectious illness. 155actobacillus-free (LF) mice were used to establish the physiological relevance of L. reuteri's immunological effects in vivo. 156,157roinflammatory cytokines and chemokines generated by intestinal epithelial cells in the ileum and jejunum were activated as a result of the administration of L. reuteri in this animal. 158urthermore, probiotics have been shown in multiple studies to strengthen the integrity of the intestinal barrier by increasing gene expression in tight junction signaling.By tight junctional protein phosphorylation, enhancing (actinin, occludin) cytoskeletal or preserving (actin, ZO-1).L. acidophilus inhibited enter invasive E. coli

Inhibition of Carcinogenesis
It is well proven that Lactobacillus can modulate-ameliorate specific mechanisms against cancers via stimulating anti-cancer effects like enhancing apoptosis of cancer cells and protecting them from oxidative stress.
P ro b i o t i c b a c te r i a , p a r t i c u l a r l y Lactobacillus microorganisms, have been reported to cause anti-cancer action through increasing apoptosis of cancer cells and the protection against oxidative stress. 160,161n similar research involving colon cancer, it was demonstrated that the administration of L. fermentum NCIMB 5221 and L. acidophilus ATCC 314 in a murine colon cancer model had been discovered to stop or slow the growth of the tumor by triggering an anti-cancer immune response. 162oreover, in mice models of colorectal cancer and melanoma, it has been shown that the administration of live L. rhamnosus GG orally enhanced the antitumor effectiveness of antiprogrammed cell death 1 (PD-1) immunotherapy by boosting tumor-infiltrating dendritic cells (DCs) and T cells. 163n addition, L. paracasei, L. casei, L. fermentum, and L. rhamnosus were the most frequently isolated species from head and neck cancer patients.moreover, L. paracasei had the highest proportion of antimicrobial activity and the best acid-producing capacity against S. mutans. 164robiotics might alter the microenvironment of the intestine, causing proinflammatory cytokines to decrease.As in the study of Zaharuddin and his group they have shown that pro-inflammatory cytokines were reduced in colorectal cancer patients by using probiotics consisting of six live Lactobacillus and Bifidobacteria strains. 165n addition, in breast cancer metastases in a mouse model, it has been shown that the fermentation of Milk by Lactobacillus casei CRL431 (probiotic fermented milk (PFM) help in breast cancer metastases by altering the immune response. 166urthermore, probiotic L. rhamnosus MD 1 produced metabiotics that exhibited both cytotoxic and antigenotoxic potential against colon cancer. 167 n o t h e r st u d y h a s s h ow n t h at lactobacillus E6-1 can inhibit the proliferation of Cal-27 and effectively induce apoptosis of tumor cells in vitro. 168he exopolysaccharide (EPS) generated by L. plantarum-12 was found to suppress the colon cancer cell line's proliferation HT-29 in humans via the mitochondrial route. 169he findings of a study about colorectal cancer (CRC) suggested that consuming Lactobacillus acidophilus in persons with polyps and people that have a family history of CRC may be a means to prevent, treat, or lower the severity of CRC. 170ecause of their activity against cervix cancer cells, other research suggests that Lactobacillus casei SR1, L. casei SR2 and L. paracasei SR4 strains derived from the breast milk of humans can be employed as topical therapy with a potential therapeutic index. 171he results of recent investigations support the hypothesis that probiotics may be used in cutting-edge cancer treatments.Therefore, to validate these findings and develop treatment plans, additional research on the subject is required.This could theoretically result in a breakthrough in many areas of medicine, including the support of immunotherapy in the treatment of cancer and the development and production of novel vaccines, as well as the improvement of drug delivery in the treatment of other bowel diseases while simultaneously preventing and reducing inflammation.

Reduction of Cholesterol level
Numerous studies have demonstrated Lactobacillus' potential to lower cholesterol levels.Such as In C57BL/6 mice fed a hypercholesterolemia diet, L. plantarum H6 lowered serum cholesterol levels.It improved the microbial community of intestinal structure in mice by preventing the pathway of farnesoid X receptor to increase the synthesis of bile acids in vivo via promoting the expression of the CYP7A1 gene. 172(Table ).
It was shown that L. plantarum YS5 can reduce the level of cholesterol by 84% due to its ability to remove cholesterol in vitro.furthermore, in male Wistar rats, probiotic supplementation was observed to lower serum total cholesterol, lowdensity lipoprotein cholesterol, and triglyceride levels. 173here is evidence that consuming probiotic-rich dairy products lowers blood cholesterol, which could help prevent diabetes, obesity, cerebral stroke, and cardiovascular disease. 174actobacillus, such as L. fermentum, L. plantarum, and L. acidophilus decrease cholesterol and ameliorate the advancement of nonalcoholic steatosis.Thus, Lactobacillus can be used as a beneficial strategy for non-alcoholic fatty liver disease (NAFLD) treatment. 175urthermore, the administration of L. rhamnosus BFE5264 resulted in a major reduction in serum cholesterol in a mouse model fed a highcholesterol diet and changes in the gut flora and the production of short-chain fatty acids were also observed (SCFA).Also, this strain has a positive impact on the metabolism of cholesterol in the liver in a manner like that resulting from statin treatment, which is a drug that can inhibit the biosynthesis of cholesterol in the liver. 176. kefiri DH5 has anti-obesity benefits via lowering the lumen cholesterol and upregulating the PPAR gene in adipose tissues. 177long the AMP-activated protein kinase (AMPK) pathway, lactobacilli could exert cholesterol-lowering properties by AMPK phosphorylation that lowered 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR) expression. 178. plantarum (LP06CC2) was tested for its effect on cholesterol metabolism in mice fed a cholesterol-rich diet.The consumption of LP06CC2 inhibited the hepatic damage indices as well as the increase of liver cholesterol.The deconjugation of bile acids was clearly boosted by LP06CC2, indicating that bile acid absorption was reduced.LP06CC2 appears to be a promising Lactobacillus for lowering cholesterol levels by modulating deconjugation of bile acid.179 Probiotics' effects on total cholesterol levels have been thoroughly studied.Researchers have made an effort to elucidate the mechanisms of probiotics on the hypocholesterolemic effect through in vitro and in vivo experiments in order to explain the variable cholesterol-lowering effect displayed by distinct probiotic strains.Numerous theoretical explanations and experimental data focusing on cholesterol-lowering effects are still debatable.Therefore, better-designed in vivo studies may reveal more information that can help resolve disagreements, better understand underlying mechanisms, and determine whether a substance is safe to consume before it is used.

Probiotics as "One Health" Perspective
According to the World Health Organization, One Health is an integrated, unified strategy aimed at continuously balancing and optimizing the health of humans, animals, and ecosystems; in order to intimately connect the interdependence of all these domains.
Increasing the risks of antibiotic resistance and pathogen transmissibility between humans and animals, changing climatic conditions, people's migrations, and increasing the rate of communication are all factors that have contributed to disease spread and will require the application of the concept of "one health."Some of the most often used antimicrobial medications in animals, for example, are likewise reserved for the most difficult cases in humans.
Beneficial domestic multi-dominant agents such as probiotics, which are used to dwell in ecosystems and organisms, can apply the "one health" principle.Ecosystems contain and maintain the most biodiversity on the planet, which may be transmitted to humans via animal and plant products.Probiotics found in soil and plants are primarily favorable to humans and animals.Probiotics, which demonstrate dynamic relationships with different bacteria across the animal and plant kingdoms, developed alongside plants, invertebrates, and vertebrates, forming mutualism, symbiosis, commensalism, or even parasitic behavior with their hosts.Lactobacillus spp., with their ability to colonize the phyllosphere, endosphere, and rhizosphere, as well as the fruits and flowers of many plants, make these probiotics species suitable for achieving the "one health" notion.
The diverse lactobacilli isolation sources, as well as the species' capacity to transmit and reside in multiple locations and habitats, enhance the implementation of the "one health" concept.Many studies have shown that Lactobacillus spp.can restore environmental balance and enhance human and animal health.For example, in human health, the remarkable flexibility and adhesion of lactobacilli in the host's gastrointestinal system may help enhancement of the host's gut health.Furthermore, lactobacilli species may be useful as plant growth promoters.Probiotics with the ability to ferment a wide range of carbohydrates, probiotic benefits on human and animal health, and are found in vegetables, dairy products, pickles, sauerkraut, cheeses, fish products, and sausages are likely the greatest candidates for "One Health." Improving the quality of animal products, increasing production and food security, and lowering the risk of pathogenic agents can all be accomplished by using probiotics as nutritional supplements in scientifically studied ways, in addition to providing an alternative solution to the use of antibiotics.Despite its critical and helpful properties, a high concentration of lactobacillus spp. in food can induce food spoilage.

CONCluSION ANd FutuRe PeRSPeCtIVeS
Almost a century after Lactobacillus species were initially characterized, researchers are constantly working to identify new Lactobacillus species from previously unknown sources.Probiotics may be found in a number of locations; however, as development techniques have been employed, scientists have begun to seek probiotics in unorthodox sources that can aid in the discovery of novel probiotic strains such as non-dairy fermented goods and inanimate surroundings.Lactose-intolerant persons are given probiotics obtained from plant sources, which also demonstrate potential new antibiotics activities of isolates that can be utilized as a replacement or supplement to current chemical antibiotics.Lactobacillus species may be separated from fermented and non-fermented biological sources, as well as from environmental sources.The lactobacilli's unique habitat features and wide range of environments indicate the possibility of searching for and isolating new lactobacillus probiotics strains from unexpected sources.
It's far viable that they may grow to be greater effective strategies inside the remedy of diverse issues which includes immune gadget stimulation, high cholesterol level, oral infections, urinary tract infections, vagina inflammation, diarrhea symptoms, and so forth as an alternative or supplement to other well-known treatments in the future.It is a natural remedy for newborn animals and humans, as well as for nutrition and sickness treatment.Aside from therapy, they are now widely used in newborn diets and milk.In terms of liver disease, lowering liver enzymes and bilirubin levels can be achieved by Lactobacilli isolated from sugar cane following the fermentation process.
Probiotics are vital for restoring normal gut flora, increasing the development of good bacteria, and decreasing the chance of acquiring chronic conditions including cardiovascular disease.As a result, there is widespread interest in these molecules as components for the development of innovative meals with functional qualities.seeking to the roles of native microbiota affecting health and balance restoration, the most current scientists in this regard are still in the early stages of discovering connections and relationships between native probiotics and intestinal microbiota, which might enable for successful customization of probiotic treatment, the commitment of supplementation time, and description of optimal doses for patients in order to improve cardiovascular efficiency or treat certain disorders.
Gut microbiome research is a young and difficult topic with methodologies that are a way to be uniform and coordinated.Massive datasets created from the microbiome, metabolomics, genomics, and transcriptomics are analyzed as consolidated investigation data could be a challenge to interpret, and a variety of complicated bioinformatics approaches have been conducted.the requirement for improving this field of inquiry is crucial through empirical and disarranged controlled studies.To increase existing understanding, well-designed clinical studies including all components of life routine, intestinal microbiome, metabolite, and genetics data are better to be improved.
Although additional clinical evidence is needed to further assess probiotics' therapeutic value, procaryotes such as Lactobacilli strains are now among the most extensively utilized agents in GIT diseases.According to in vivo investigations, Lactobacillus survives well in the human GI tract.Lactobacilli are one of the most common LAB species that have played important therapeutic functions since their discovery.The increasing amount of research shows that it may be beneficial for diarrhea prevention and alleviation, as well as the treatment of recurring Clostridium difficile colitis.
By upgrading methodologies, tools, and techniques for isolation and identification, new pathways for probiotics will open, resulting in additional discoveries of local probiotic strains.New approaches, such as those that enable realtime human study and monitoring of a microbe's integration into an established microbiome, are being developed, along with technologies capable of assessing hit points, which can move this area ahead.after moving on to physical tests henceforth, information on the presence of bacteria, their interaction with the host, and the effect of environmental stimuli (including medications, and nutrition) going to be routine.revolutionary pattern technology will disclose how a probiotic interacts with the host in several stages such as immune machine, all microbiome components, and metabolism.The integrated approach will aid in the establishment of doseresponse connections for diagnosis, as well as in coordinating what gets into our systems, which probiotic bacteria have the most predicted impact, and how they will be absorbed.
Probiotic strains isolated from marine organisms have several applications and can be used for Aquaculture species and to prevent microbial pathogens that could threaten marine life.Studies that aim to isolate novel strains of probiotics from aquatic organisms present alternative treatments for the human and marine organisms' pathogens and shed the light on the significant importance to intensify research for probiotics isolated from marine organisms in the future.

Figure 1 .
Figure 1.Diagram of various sources of lactobacillus spp.identified as probiotics

table .
Uses of Lactobacillus spp. as probiotic against various human diseases.the clinical outcomes had been conducted on humans as a subject