Encyclopedia
Multi-strain probiotics are composed of more than one species or strains of bacteria and sometimes, including some fungal species with benefits to human and animals’ health. The mechanisms by which multi-strain probiotics exert their effects include cell-to-cell communications, interactions with the host tissues, and modulation of the immune systems.
- antibiotics
- probiotics
- cell-cell communication
- synergy
- antagonism
1. Introduction
The Food and Agriculture Organization/World Health Organization (FAO/WHO) working committee on probiotics defined probiotics as “live microorganisms which when administered in adequate amounts confer health benefits on the host” [1]. The use of probiotics is increasing due to consideration as a suitable option following restrictions on antibiotics as growth promoters in the livestock industries by many countries [2]. There are different forms of probiotics preparations, and sometimes, their efficacy depends on whether they are single- or multi-strain preparations [3]. Compared to single-strain preparations, multi-strain probiotics contain more than one strain of the same species, genera, or multiple genera and sometimes including both bacteria and fungi (
The Food and Agriculture Organization/World Health Organization (FAO/WHO) working committee on probiotics defined probiotics as “live microorganisms which when administered in adequate amounts confer health benefits on the host” [1]. The use of probiotics is increasing due to consideration as a suitable option following restrictions on antibiotics as growth promoters in the livestock industries by many countries [4]. There are different forms of probiotics preparations, and sometimes, their efficacy depends on whether they are single- or multi-strain preparations [14]. Compared to single-strain preparations, multi-strain probiotics contain more than one strain of the same species, genera, or multiple genera and sometimes including both bacteria and fungi (
Saccharomyces species) [4]. Some single-strain probiotics are beneficial in alleviating gastrointestinal-tracts-associated diseases [5]. However, previous
species) [15]. Some single-strain probiotics are beneficial in alleviating gastrointestinal-tracts-associated diseases [16]. However, previous
in-vitro studies showed that some multi-strain probiotics could exhibit better inhibitory effects on entero-pathogens [6] and enhanced benefits by combining effects of different strains compared to their single-strain preparations [7].
studies showed that some multi-strain probiotics could exhibit better inhibitory effects on entero-pathogens [17] and enhanced benefits by combining effects of different strains compared to their single-strain preparations [18].
2. Mechanisms of Action of Probiotics
The mechanism of probiotics' actions is the various means by which they exert their beneficial effects on the host, including immune modulation, stimulation/modulation of gut microbiota, stimulation of digestive enzymes, displacement of pathogens, and production of bioactive compounds [8][9][10]. The gut-associated actions are the principal effects of probiotics, also regarded as the basis of other health benefits [11] as summarized in
The mechanism of probiotics’ actions is the various means by which they exert their beneficial effects on the host, including immune modulation, stimulation/modulation of gut microbiota, stimulation of digestive enzymes, displacement of pathogens, and production of bioactive compounds [24,25,26]. The gut-associated actions are the principal effects of probiotics, also regarded as the basis of other health benefits [27] as summarized in
.
Figure 1.
shows the mechanism of actions of probiotics: the intake of probiotics stimulates an increase in the secretion of mucus by goblet cells, mobilization of intraepithelial leucocytes, and tightening of the tight junctions to protect against the invasion of pathogens. The increase in mucus secretion and improvement of gut microbiota enhances competitive displacement and inhibition of pathogens adhesion to the gut epithelial surface. Furthermore, the action of bioactive substances such as lysozyme and cytokines stimulate phagocytosis by macrophages.
3. Applications and Biological Functions of Multi-Strain Probiotics
3.1. Treatment of Diseases
Different randomized control clinical trials revealed that some specific probiotics are useful in the therapeutic management of gastrointestinal (GI) illnesses like inflammatory bowel disease (IBD) [12], irritable bowel syndrome (IBS), and pouchitis [13][14]. The administration of multi-strain probiotics containing different
Different randomized control clinical trials revealed that some specific probiotics are useful in the therapeutic management of gastrointestinal (GI) illnesses like inflammatory bowel disease (IBD) [34], irritable bowel syndrome (IBS), and pouchitis [87,88]. The administration of multi-strain probiotics containing different
Lactobacilli
species,
Streptococcus
and
Bifidobacterium, to patients who have systemic sclerosis alleviates the symptoms of gastrointestinal reflux and increased microbial alpha diversity group [14] (
to patients who have systemic sclerosis alleviates the symptoms of gastrointestinal reflux and increased microbial alpha diversity group [88] (
).
| Probiotics Mixture | Conditions | Mechanism of Actions | References |
|---|
| B. bifidum | W23, | B. lactis | W52, | L. acidophilus | W37, | L. brevis | W63, | L. casei | W56, | L. salivarius | W24, | Lactococcus lactis | W19 and | L. lactis | W58 | Endotoxins | Improvement of endothelial barrier, inhibition of mast cell, activation of proinflammatory cytokines, and decrease endotoxin | [15] | [94] | ||
| L. acidophilus | , | L. casei | , | B. bifidum | , and | L. fermentum | Cognitive function in Alzheimer’s disease | [16] | [93] | ||||||||||||
| L. paracasei | DSM 24,733, | L. plantarum | DSM 24,730, | L. acidophilus | DSM 24,735, and | L. delbrueckii | subspecies | bulgaricus | DSM 24,734), Bifidobacteria ( | B. longum | DSM 24,736, | B. breve | DSM 24,732, and | B. infantis | DSM 24,737), and Streptococcus ( | S. thermophilus | DSM 24,731) | Systemic sclerosis-associated gastrointestinal disease | Improvement of GI reflux and intestinal microbiota alpha diversity | [17] | [89] |
| L. acidophilus | LaVK2 and | B. bifidum | Bbvk3 | Dextran sodium- sulphate salt-induced ulcerative colitis in mice | Reduction in myeloperoxidase activity, levels of TNF-α, IL-6, and IFN-γ | [18] | [96] | ||||||||||||||
| L. bulgaricus | 151 and | S. thermophilus | MK-10 | Dextran sodium- sulphate salt-induced colitis | Modulation of intestinal microbiota, decrease the content of putrefactive short-chain fatty acid, enhanced production of cytokines. | [19] | [28] | ||||||||||||||
| B. bifidum | (KCTC 12199BP), | B. lactis | (KCTC 11904BP), | B. longum | (KCTC 12200BP), | L. acidophilus | (KCTC 11906BP), | L. rhamnosus | (KCTC 12202BP) and | S. thermophilus | (KCTC 11870BP) | Irritable Bowel Syndrome (IBS) | Alleviation of IBS symptoms and improvement of intestinal microbiota | [20] | [90] | ||||||
| B. longum | and | L. casei | strain Shirota | Treatment of obesity | Decreased weight and triglyceride in rats fed with the high-fat diet. | [21] | [106] | ||||||||||||||
| S. boulardii | , | L. acidophilus | , | L. plantarum | , | B. lactis | IBS associated with bacterial overgrowth and constipation | Improvement in bloating, and pain associated with constipation | [22] | [91] | |||||||||||
| L. plantarum | , | B. breve | , and | L. fermentum | high-dietary fat-induced obesity and | E. coli | challenged | Causes reduced Lipopolysaccharide and IL-1β, improved the structure of intestinal flora and increased the fecal short-chain fatty acid (SCFA) content | [23] | [107] |
3.2. Inhibition of Pathogens
A multi-strain probiotic containing different Lactobacillus strains hinders the adhesion of E. coli and E. faecalis to the bladder cell lines, unlike the single-probiotics preparations [24][33] (Table 2).
| Multi-Strain Probiotics Isolates | Pathogenic Bacteria | Host | References |
|---|
| B. subtilis | and | L. mesentroides | Vibrio cholereae | In-vitro agar diffusion test | [25] | [2] | |||||||||||||||||||||||||||||
| L. plantarum | F44, | L. paracasei | F8, | B. breve | 46 and | B. lactis | Clostridium difficile | Mice | [26] | [99] | |||||||||||||||||||||||||
| S. oralis | and | S. salivarius | Biofilm ( | S. aureus | , | S. epidermidis | , | S. pneumoniae | , | S. pyogenes | , | Propionibacterium acnes | and | Moraxella catarrhalis | Dogs | [27] | [109] | ||||||||||||||||||
| L. acidophilus | LAP5, | L. fermentum | P2, | P. acidophilus | LS, and | L. casei | L21 | S. enterica | subspecies | Enterica | Chickens | [28] | [9] | ||||||||||||||||||||||
| L. acidophilus | LA-5 and | B. bifidum | BB-12 | P. stomatis | , | P. multocida | , | P. canis | , | N. animaloris | , and | N. zoodegmatis | [29] | [116] | |||||||||||||||||||||
| P. acidilactici | and | S. cerevisiae boulardii | Enterotoxigenic | E. coli | (ETEC) F4 | Pigs | [30] | [38] | |||||||||||||||||||||||||||
| L. acidophilus | NCIMB 30184, | L. fermentum | NCIMB 30226, | L. plantarum | NCIMB 30187, and | L. rhamnosus | NCIMB 30188 | Pathogenic | E. coli | and | E. faecalis | [24] | [33] | ||||||||||||||||||||||
| S. cerevisiae | , | E. faecium | , | L. acidophilus | and | Bacillus subtilis | E. coli | Chickens (broilers) | [31] | [117] | |||||||||||||||||||||||||
| L. acidophilus | NCIMB 30184, | L. rhamnosus | NCIMB 30188, | L. plantarum | NCIMB 30187, | L. delbrueckii | ssp. bulgaricus NCIMB 30186, | L. casei | NCIMB 30185, | L. lactis | NCIMB 30222, | L. salivarius | NCIMB 30225, | L. fermentum | NCIMB 30226, | L. helveticus | NCIMB 30224, | B. bifidum | NCIMB 30179, | B. breve | NCIMB 30180, | B. infantis | NCIMB 30181, | B. longum | NCIMB 30182, | S. | thermophilus NCIMB 30189 | B. subtilis | NCIMB 30223 | S. typhimurium | , | C. difficile | In-vitro distal colon model | [32] | [118] |
| L. acidophilus | NCIMB 30184, | L. fermentum | NCIMB 30188, | L. plantarum | NCIMB 30187 and | L. rhamnosus | NCIMB 30226 | E. faecalis | NCTC 0075 and | E. coli | NCTC 9001 | In-vitro agar diffusion test | [6] | [17] | |||||||||||||||||||||
| L. rhamnosus | and | L. reuteri | Vaginal coliforms and yeast | Human (female) | [33] | [104] | |||||||||||||||||||||||||||||
| L. crispatus | , | L. salivarius | , | L. gallinarum | , | L. johnsonii | , | E. faecalis | and | B. amyloliquefaciens | Salmonella | Enteritidis A9 | Chickens (broiler) | [34] | [40] | ||||||||||||||||||||
| L. acidophilus, L. fermentum | , | L. plantarum | and | E. faecium | Salmonella enterica | Chickens (broiler) | [35] | [42] | |||||||||||||||||||||||||||
| B. amyloliquefaciens | B-1895 and | B. subtilis | KATMIRA1933 | Inhibits | Proteus mirabilis | biofilm formation | Invitro | [36] | [84] | ||||||||||||||||||||||||||
| E. faecalis | (strains NM815, and NM915) and | E. faecium | NM1015 | C. difficile | infection | Mice | [37] | [103] | |||||||||||||||||||||||||||
| L. acidophilus | (LA-5), and | B. animalis | subspecies | Lactis | (Bb12) | E. coli | induced pyelonephritis | Sprague-Dawley rat | [38] | [112] | |||||||||||||||||||||||||
| L. casei | and | E. faecium | Entamoeba invadens | Invitro | [39] | [115] | |||||||||||||||||||||||||||||
| B. subtilis, L. acidophilus | , | P. acidilactici | , | P. pentosus | , | Saccharomyces pastorianus | Avian pathogenic | E. coli | and | Salmonella | Kentucky | White leg-horn chicks | [40] | [113] | |||||||||||||||||||||
| L. gasseri | and | L. rhamnosus | Non- | Candida albicans | biofilm formation | In-vitro | [41] | [110] |
3.3. Improvement of Human Health
Multi-strain probiotics had proved beneficial for the treatment of dysentery in addition to the standard regimen with a marked reduction in the extent of bloody stooling and a decreased average length of hospital stay [42]. These effects were a result of the alteration of the microbial and metabolic activities within the gut, and which are enough to modify the disease process and pathological conditions [43].
Multi-strain probiotics had proved beneficial for the treatment of dysentery in addition to the standard regimen with a marked reduction in the extent of bloody stooling and a decreased average length of hospital stay [123]. These effects were a result of the alteration of the microbial and metabolic activities within the gut, and which are enough to modify the disease process and pathological conditions [124].
3.4. Multi-Strains Probiotics in Animal Husbandry
Probiotics may be a potential alternative for improving gastrointestinal health and growth promotion in different animal species [44]. Based on these, the roles of probiotics in the various livestock sub-sectors, including poultry, aquaculture, piggery, and ruminant nutrition, were discussed as follows.
Probiotics may be a potential alternative for improving gastrointestinal health and growth promotion in different animal species [86]. Based on these, the roles of probiotics in the various livestock sub-sectors, including poultry, aquaculture, piggery, and ruminant nutrition, were discussed as follows.
3.5. Poultry Farming
In poultry, the addition of probiotics derived from
Lactobacillus, Bacillus [45], and
[127], and
Clostridium species to feed has a positive impact on the growth yield, feed digestion [46], immunity [47], meat quality [48], and coliforms bacterial count [44][49]. The administration of multi-strain probiotics (comprising of
species to feed has a positive impact on the growth yield, feed digestion [128], immunity [129], meat quality [130], and coliforms bacterial count [86,131]. The administration of multi-strain probiotics (comprising of
L. acidophilus
LAP5,
L. fermentum
P2,
P. acidophilus
LS, and
L. casei
L21) to specific-pathogen-free (SPF) chicks infected with
Salmonella enterica
subspecies
enterica decreases the abundance of proteobacteria of which Salmonella is a member [28].
decreases the abundance of proteobacteria of which Salmonella is a member [9].
3.6. Aquaculture
The use of probiotics for health improvement has also found application in aquaculture. The addition of multi-strain probiotics in the feed of rohu (
Labeo rohita) was revealed to stimulate cellulolytic and amylolytic enzymes secretions with improved growth output [50]. The multi-strain culture of
) was revealed to stimulate cellulolytic and amylolytic enzymes secretions with improved growth output [137]. The multi-strain culture of
B. subtilis
,
B. licheniformis
, and
lactobacilli
probiotics significantly improves pacific white shrimps’ growth (
Litopenaeus vannamei
) and enhances non-specific immunity and the abundance of
Bacillus to influence the intestinal microbiota [51].
to influence the intestinal microbiota [30].
3.7. Swine Production/Piggery
The weaning period in piggery coupled with diets changes from simply digestible (milk) to solid feeds may result in intestinal perturbation, thereby causing diarrhea and a slow growth rate [52][53][54]. The ingestion of probiotic bacteria (like
The weaning period in piggery coupled with diets changes from simply digestible (milk) to solid feeds may result in intestinal perturbation, thereby causing diarrhea and a slow growth rate [141,142,143]. The ingestion of probiotic bacteria (like
P. acidilactici
) and yeast (
S. cerevisiae boulardii) protect from microbial infection by enhancing intestinal defences and performance in different monogastric animals [55].
) protect from microbial infection by enhancing intestinal defences and performance in different monogastric animals [146].
3.8. Ruminants Nutrition and Production
Some probiotics are suitable supplements in livestock feeds and may improve the rumen’s microbial ecosystem, enhance feed digestion, and restores gut microflora in diarrhea in ruminants [56]. The administration of lactobacilli probiotics enhances calves’ overall health status [57].
Some probiotics are suitable supplements in livestock feeds and may improve the rumen’s microbial ecosystem, enhance feed digestion, and restores gut microflora in diarrhea in ruminants [149]. The administration of lactobacilli probiotics enhances calves’ overall health status [150].
3.9. Synbiosis of Multi-Strain Probiotics with Other Biologically Active Molecules
Some probiotics are prepared as synbiotics (prebiotics) along with other active substances for maximum physiological effects. Ingestion of synbiotics made of multi-strain probiotics (containing
L. acidophilus
strain T16,
L. casei
strain T2 and
B. bifidum strain T1) and 800 mg inulin (HPX) by gravid women with gestational diabetes mellitus decrease the rate of caesarean section and hyperbilirubinemia and hospitalization of newborns [58]. Administration of synbiotics (containing multi-strain probiotics and prebiotics) may alleviate some digestive system conditions, sepsis, and death in preterm babies [59] (
strain T1) and 800 mg inulin (HPX) by gravid women with gestational diabetes mellitus decrease the rate of caesarean section and hyperbilirubinemia and hospitalization of newborns [156]. Administration of synbiotics (containing multi-strain probiotics and prebiotics) may alleviate some digestive system conditions, sepsis, and death in preterm babies [157] (
).
| Synbiotics | Actions | Host | References |
|---|
| L. acidophilus | strain T16, | L. casei | strain T2) and | B. bifidum | strain T1 plus 800mg inulin (HPX) | decreased the incidence of cesarean section rate and newborn’s hyperbilirubinemia and hospitalization | Human (pregnant women) | [58] | [156] | |||||||
| L. acidophilus | , | L. rhamnosus | , | S. thermophilus | , and | L. delbrueckii | subspecies | Bulgaricus | plus fluconazole | Enhance the treatment of Vaginal candidiasis caused | Candida albicans | humans | [60] | [158] | ||
| L. plantarum, L. acidophilus, L. delbrueckii subspecies bulgaricus, B. bifidum, L. rhamnosus, E. faecium, S. salivarius subspecies thermophilus, Aspergillus oryza | , and Candida | pintolopesii | plus Zinc | Enhances growth performance, better feed utilization, increase in villus height in the duodenum and ileum | Chicken (broiler) | [61] | [159] | |||||||||
| Synbiotics A: | Enterococcus | sp., | Pediococcus | sp., | Bifidobacterium | sp., | Lactobacillus | sp. plus fructooligosaccharides Synbiotic B: | L. acidophilus, L. casei, L. salivarius, L. plantarum, L. rhamnosus, L. brevis, B. bifidum, B. lactis, S. thermophilus | , prebiotic inulin (chicory root extract), protease, amylase, cellulase, hemicellulase, lipase, papain and bromelain | Modulate the caecal microbiota without any effects on Salmonella | Typhimurium | shedding | Chickens (layers) | [62] | [65] |
| Probiotics; ( | L. rhamnosus, L. casei L. plantarum B. animalis | ) prebiotics (383 mg of fructooligosaccharides and 100 mg of galactooligosaccharides) | Improved gastrointestinal complications, sepsis, and mortality in premature infants | Preterm infants | [59] | [157] |
4. Future Consideration
To maximize all the benefits of probiotics consumption, research should determine the specific mechanisms of actions of probiotics microbes for more specific applications in respective disease conditions. There is also the need to study and understand each probiotics strain’s best combination because some bacteria act synergistically, some additively, and some antagonistically. Additionally, the bioactive substances produced by some probiotics could be extracted to formulate supplements for use in specific conditions where individuals showed some reactions to the consumption of the whole-cells preparations. The harvesting and harnessing of the bioactive substances produced by individual constituents of mixed probiotics could also solve the challenges associated with the inconsistency of viable cells when live microbes are used. That will also enable large-scale production for commercialization. Finally, further studies in this direction could be an essential factor in the future research and development of multi-strain probiotics.
