Probiotic Efficacy and Potential of Streptococcus thermophilus modulating human health: A synoptic review

Abstract

The use of probiotic bacterial cultures stimulates the growth of preferred microorganisms, crowds out potentially harmful bacteria, and reinforces the body's natural defence mechanisms. Streptococcus thermophilus has been exploited industrially for making cheese as well as yogurt. One of the most important properties of this bacterium which is being used is production of lactase, an enzyme that converts lactose (milk sugar) into a simple sugar, which helps people who are lactose intolerant to digest milk. So consumption of this microbe has facilitated to alleviate symptoms of lactose intolerance and other gastrointestinal problems. Due to this unique feature of the microbe, it has been added to several health supplements along with other bacteria with similar properties. Over and above, it also produces a variety of antagonistic factors that include metabolic end products, antibiotic-like substances and bactericidal proteins, termed bacteriocins which assist to prevent several types of infections from various pathogenic microbes. In addition, the bacterium is endowed with enormous important beneficial properties. The following review will discuss with some beneficial aspects of S. thermophilus.

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IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS)
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Probiotic Efficacy and Potential of Streptococcus thermophilus
modulating human health: A synoptic review
Rohit Sharma1*, 2, Bhuvan Bhaskar1, Bhagwan S. Sanodiya1, Gulab S. Thakur1,
Pallavi Jaiswal1, Nitin Yadav1, Anjana Sharma2 and Prakash S Bisen1, 2
1*(Microbial Biotechnology Laboratory, R&D Division, Tropilite Foods Pvt Ltd, Davars Campus, Tansen Road,
Gwalior- 474002, India)
2(Department of Post Graduate Studies and Research in Biological Sciences, Rani Durgavati Vishwavidyalaya,
Jabalpur – 482004, India)
Abstract: The use of probiotic bacterial cultures stimulates the growth of preferred microorganisms, crowds
out potentially harmful bacteria, and reinforces the body's natural defence mechanisms. Streptococcus
thermophilus has been exploited industrially for making cheese as well as yogurt. One of the most important
properties of this bacterium which is being used is production of lactase, an enzyme that converts lactose (milk
sugar) into a simple sugar, which helps people who are lactose intolerant to digest milk. So consumption of this
microbe has facilitated to alleviate symptoms of lactose intolerance and other gastrointestinal problems. Due to
this unique feature of the microbe, it has been added to several health supplements along with other bacteria
with similar properties. Over and above, it also produces a variety of antagonistic factors that include
metabolic end products, antibiotic-like substances and bactericidal proteins, termed bacteriocins which assist to
prevent several types of infections from various pathogenic microbes. In addition, the bacterium is endowed
with enormous important beneficial properties. The following review will discuss with some beneficial aspects
of S. thermophilus.
Key Words: Streptococcus thermophilus, Probiotic, Lactose intolerance, Microflora, Dysbiosis, Bacteriocins
I. Introduction
The term probiotic means “for life” and it denotes the bacteria beneficial for humans and animals. The
original observation of the positive role played by some selected bacteria is attributed to Elie Metchnikoff, the
Russian born Nobel Prize recipient working at the Pasteur Institute, who suggested that "The dependence of the
intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to
replace the harmful microbes by useful microbes"[1]. Fuller (1989) [2], pointing out towards the microbial
nature of probiotics, redefined the term as "A live microbial feed supplement which beneficially affects the host
animal by improving its intestinal balance". A more recent, but probably not the last definition is "live
microorganisms, which when consumed in adequate amounts, confer a health effect on the host" [3]. Exploiting
the probiotic bacteria has been proved beneficial as a potential preventive measure by providing a microbial
stimulus to the host immune system by administering microorganisms that are characteristics of the healthy,
human gut microflora. And as such research diversifies; one particular bacterial strain has attracted and is
receiving special attention – Streptococcus thermophilus which comes to our diet through variety of fermented
products. S. thermophilus is a Gram-positive bacterium belonging to the phylum Firmicutes, family
Streptococcaceae and order Lactobacillales. It belongs to the clade of Lactic acid bacteria which include the
species of genera Carnobacterium, Enterococcus, Lactobacillus, Lactococcus, Leunostoc, Oenococcus,
Pediococcus, Tetragenococcus, Vagococcus and Weissella [4]. S. thermophilus is closely related to Lactococcus
lactis, but it is even more closely related to other streptococcal species including several pathogens [5]. S.
thermophilus is highly adapted to grow on lactose, the main carbon source in milk and rapidly converts it into
lactate during growth. Lactose is transported into the cell by a lactose permease (LacS), which operates as a
galactosideproton symport system or as a lactose-galactose antiporter. Lactose is efficiently transported into the
cell and subsequently hydrolyzed by an intracellular b-galactosidase. The vast majority of S. thermophilus
strains only metabolized the glucose moiety of lactose, while galactose is excreted into the medium. The milk is
poor in free amino acids (AA) and short peptides, therefore for optimal growth; S. thermophilus requires either
hydrolysis of caseins followed by the internalization and the degradation of the resulting peptides or de novo
AA biosynthesis [6]. For many LAB including S. thermophilus, the hydrolysis of milk caseins (i.e. the AA
supply) mostly depends on the activity of a cell-wall-anchored proteinase [7]. S. thermophilus and L. bulgaricus,
lead to positive effects on the yogurt taste and aroma by symbiotic coexistence, described by the ecological term
protocooperation (where two species interact with each other beneficially). Protocooperation is basis for
creation of symbiotic relation between the two species (S. thermophilus and L. bulgaricus) and combined
metabolism with positive effects on the fermented product. Streptococcus strain produces formic acid promoting

Probiotic Efficacy and Potential of Streptococcus thermophilus modulating human health: A synoptic
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the growth of the Lactobacillus which, on its turn, provides flavour compounds (acetaldehyde) and the
proteolytic activity to keep the Streptococcus strain growing in milk [8]. The genus Streptococcus includes
Gram positive bacteria with similar metabolic properties but they live in different habitats and have many
physiological differences. In the past two decades, several important Streptococcus species have been
reclassified as members of recently named genera Enterococcus and Lactococcus. The only dairy streptococcus
remained is S. thermophilus. Streptococci grouped as “oral”, “pyogenic” and “other streptococci”. “Oral”
streptococci are also subdivided into four groups; S. mutans, S. mitis, S. anginosus and S.thermophilus groups
[9]. Although S. thermophilus is a member of “S. thermophilus group” phylogenetically, it is the only bacterium
in Streptococci with dairy origin. The Gram positive and cocci genera sharing the same habitat with S.
thermophilus includes enterococci, lactococci, pediococci and leuconostocs. The pediococci is readily
distinguished from other genera by the tetrad morphology in broth media. Some of the physiological differences
which are helpful for the first grouping at the genus level are given in the table below:
Table: Classification of cocci lactic acid bacteria
Microrganism
Growth
at 10°C
Growth
at 45°C
Growth in
6.5% NaCl
Type Lactate
formed
Gas from
Glucose
Growth in
broth at pH
9.6
Arginine
Hydrolysis
Enterococcus
+
+
+
ND
-
+
+
Lactococcus
+
-
-
L
-
-
V
Streptococcus
-
+
-
L
-
-
V
Leuconostoc
+
+
-
D
+
ND
-
* ND indicates no data available, V indicates variable: some produce (+) results and some (-), L indicates levo-
lactic acid and D indicates dextro-lactic acid
S. thermophilus is highly adapted to the dairy environment, and in the wild. It can only be isolated from
dairy products. S. waius is a recently identified thermophilic Streptococcus isolated from stainless still
pasteurization machinery of milk. It shares many phenotypic characteristics with S. thermophilus but can be
distinguished by the fermentation of galactose, salicin, cellobiose, maltose, melibiose and D-raffinose [10].
Characteristics of Streptococcus thermophilus B4 isolated from Goat Milk (Sharma et al 2013) [10]
Gram
Staining
Cell Morphology
Spore
Formation
Catalase
Activity
Fermentation
Type
Glucose
Fermentation
Nitrate
Reduction
Positive
Cocci in chains
Negative
Negative
Homo
Positive
Negative
Sugar Fermentation Streptococcus thermophilus B4 isolated from Goat Milk (Sharma et al 2013) [10]
Sucrose
Lactose
Maltose
Dextrose
Ribose
Sorbitol
Mannose
Positive
Positive
Positive
Positive
Negative
Negative
Positive
II. History And Nomenclature
The name Streptococcus is derived from the Greek word which means “twisted berry” it is seen under
the microscope as a chain that resemble a string of beads. Thermophilus is a Greek term which means heat,
referring to an organism that is able to survive extreme cases of heat. Orla-Jensen (1919) [11] was the first to
differentiate and describe S. thermophilus as a distinct streptococcal species. S. thermophilus is classified as a
nonpathogenic, single Streptococcus species to possess a generally recognized as safe (GRAS) status [12]. It is
also considered as “the second most important industrial dairy starter after Lactococcus lactis” [13]. Along with
the use in manufacturing fermented food, streptococcus is reported to posses probiotic properties in adequate
amount conferring a health benefit to the host [14, 15, 47].
Table1: Characteristics of Lactobacillus bulgaricus & Streptococcus thermophilus [16]
III. S. thermophilus As Dairy Starter
Characteristics of microbes
Lactobacillus bulgaricus
Streptococcus thermophilus
Growth on MRS agar at pH 6.3
Positive
Positive
Growth on MRS agar at pH 5.4
Positive
Negative
Incubation Temperature
30oC
42oC
Catalase activity
Negative
Negative
Gram reaction
Positive
Positive
Cell morphology
Rods
Cocci
Colony size
Small
Big
Colony shape
Circular, irregular
Circular,
Colony colour
Creamy grey
Irregular, Creamy white

Probiotic Efficacy and Potential of Streptococcus thermophilus modulating human health: A synoptic
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A starter culture can be defined as a microbial preparation of large numbers of cells of at least one
microorganism to be added to a raw material to produce a fermented food by accelerating and steering its
fermentation process. S thermophilus is extensively used in starter cultures for dairy products like Swiss and
Italian-type cheeses, Gouda cheese and yoghurt because of its metabolical traits such as production of lactic
acid, flavouring compounds, exopolysaccharide production, fermentation of galactose, urease and proteolytic
activity, [17]. A recent study conducted at National Dairy Research Institute, India shows that S thermophilus
isolated from plant sources possess similar physiological and biochemical properties to those from dairy sources
and can be considered for developing new starters [52].
IV. Antibacterial Activity Against Intestinal Microbes
S. thermophilus along with other probiotic bacteria possess inhibitory effects on some of intestinal
pathogenic organisms and hence it is evident that it can be administered in order to prevent or ameliorate some
diseases.
Table 2: Measurement of antimicrobial activity (zone of inhibition in mm) of Lactobacillus bulgaricus and
Streptococcus thermophilus against clinical isolates. (Adapted from [16])
Indicator organisms
Zone of inhibition(in mm)
Escherichia coli
4.0
Klebsiella sp.
4.2
Pseudomonas sp.
1.6
Proteus sp.
2.3
Salmonella sp.
0
Shigella sp.
1.8
V. Efficacy Against Antibiotic Associated Diarrhoea
In a study conducted to determine the efficiency of probiotic drink (containing S. thermophilus along
with Lactobacillus casei ,and L. bulgaricus) for the prevention of diarrhoea associated with use of antibiotics
and that caused by Clostridium difficale , it was found to reduce the incidence of AAD and also having the
potential to decrease morbidity, healthcare costs and mortality if used routinely in patients of age greater than 50
[18].
VI. Efficacy Against Rotavirus Induced Diarrhoea In Infants
Rotavirus-induced diarrhea poses a worldwide medical problem in causing substantial morbidity and
mortality among children in developing countries, and the development of preventive measures remains an
important goal. In a double-blind, placebo-controlled trial, infants aged 5-24 months who were admitted to a
chronic medical care hospital were randomised to receive a standard infant formula or the same formula
supplemented with Bifidobacterium bifidum and S. thermophilus. It was found that the supplementation of infant
formula with B. bifidum and S thermophilus can reduce the incidence of acute diarrhoea and rotavirus shedding
in infants admitted to hospital [19].
VII. Role In Enteric Dialysis For Renal Failure
In a test conducted for the formulation of commensal and food grade bacteria that when ingested may
become gut flora that catabolize nitrogenous toxins that accumulate in uremia flow into the gut by passive
diffusion, an isolate S. thermophilus KB19 reduced urea concentration from 300mg/dL to 20mg/dL within 24
hours at pH 6.3 when inoculated in Artificial Intestinal Fluid at initial density of 109 cfu/ml. KB19 survived 3
hours in acidic pH 3.0 with only two logs loss in cfu and was able to pass through bile. In addition, this strain
evinced no resistance to 8 commonly used antibiotics. These data indicate that S. thermophilus bacterial isolate
can be used as a urea-targeted component in an enteric dialysis formulation [20].
VII. S. thermophilus for Skin Ailments
One of the most significant health benefits associated with the use of S. thermophilus bacteria in
humans is the bacterium’s ability to exert a positive effect upon the body’s ceramide (a skin protective agent)
levels. As shown in a recent study, which demonstrated the efficacy of the bacterium in vitro and in vivo? In
vitro, it has shown a considerable positive impact on the ceramide levels measured in cultured human
keratinocytes which have function in the formation of a barrier against environmental damage such as
pathogens, heat, UV and water loss. Secondly in vivo, it has shown an equally beneficial effect on the level of
ceramides in stratum corneum, which forms a barrier to protect underlying tissue from infection, dehydration,
exposure to chemicals and mechanical stress [21]. Additionally, S. thermophilus has been found to positively
influence the levels of sphingolipids in human skin. A study which looked at about 11 patients who were

Probiotic Efficacy and Potential of Streptococcus thermophilus modulating human health: A synoptic
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treated with topical creams containing S. thermophilus, in all cases there were “significant improvements in
levels of bacterial sphingomyelinase” [22].
VIII. Reduction In Colonization Of Nasal Pathogenic Bacteria
As obtained a study which looked upon the specific measurement of pathogenic bacteria in human
nasal canals, the results showed that those patients who were given the supplemented yogurt experienced a
markedly reduced level of nasal colonization of pathogenic bacteria – Staphylococci aureus, Streptococcus
pneumonia and β haemolytic streptococci [23].
IX. S. thermophilus In Cholestrol Assimilation
Fifty four volunteers participated in a randomised cross over trial; the results of which revealed
reductions of between 5-10 % in serum cholesterol levels after several weeks of moderate consumption of
yoghurt fermented with L. bulgaricus and S.thermophilus [24].
X. S. thermophilus As Antioxidant
The damage caused to our cells and tissues by the free radicals has a critical role in progression of
disease and process of ageing. Antioxidants act as first line of defence against the damage caused due to free
radicals and thus are vital for optimal health maintenance .The antioxidant defence mechanism in the body is
composed not just of endogenousantioxidants but also of exogenous antioxidants from several food sources
(vitamins C and E,carotenoids, pholates, flavonoids, phytoestrogens and selenium). It has been recently
demonstrated that the probiotic microorganisms can effectively trap reactiveforms of oxygen as such in the
experiment conducted using rats which were deficient in vitamin E, has revealed that theintracellular extract
from Lactobacillus sp. recovers this deficiency. The classical yoghurt bacteria L. bulgaricus and S. thermophilus
inhibit peroxidation of lipids through scavenging the reactive oxygenradicals, such as hydroxyl radical, or
hydrogen peroxide [25].
XI. Mucositis In Rats
A 2009 study in Adelaide, Australia has shown very positive results when S. thermophilus TH-4 was
used to treat rats with mucositis (inflammation and ulceration of the mucous membranes) caused by
chemotherapy drugs. Rats responded to the treatment by showing a normalization of healthy cell function in the
affected areas and a significant reduction of distress to the tissue of the intestines [26]
XII. S. thermophilus In Folic Acid Production
While growing in milk, S. thermophilus is found to produce folic acid which is essential for numerous
biological functions and becomes a vital component of yoghurt [27, 28]
XIII. Bacteriocin Production By S. thermophilus
Bacteriocins are proteins produced by certain bacteria having a characteristic feature of inhibiting the
growth of similar or closely related bacterial strains The incorporation of bacteriocins as a biopreservative
ingredient into model food systems has been studied extensively and has been shown to be effective in the
control of pathogenic and spoilage microorganisms [29]. Several strains of S. thermophilus have been found to
produce bacteriocins which are being discussed in the following table:
Table 3: Summary of bacteriocins obtained from S. thermophilus and their antimicrobial activity
Strain
Bacteriocin
Inhibitory Action
against
Reference
S. thermophilus ST134
Thermophilin A
sensitive cells in the culture
[30, 31]
S. thermophilus 347
Thermophilin 347
Listeria monocytogenes
[32]
S. thermophilus Sfi 13
Thermophilin 13
L. monocytogenes
[33]
S. thermophilus 81
Thermophilin 81
Lactococcus lactis, S. typhimurium, E. coli,
[34]
S. thermophilus ACA-
DC 0040
Thermophilin T
Clostridium sporogenes,C. tyrobutyricum
[35]
S. thermophilus ACA-DC0001
Thermophilin ST-1
L.innocua,Staphylococcus
aureus , Enterococcus faecalis
[36]
S. thermophilus 580
Thermophilin 580
C. tyrobutyricum
[37]
S. thermophilus ST110
Thermophilin 110
Pediococcus acidilactic
[38]

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S. thermophilus
SBT1277
Thermophilin 1277
C. butylicum, C. sprogenes, B. cereus
[39]
S. thermophilus LMD-9
Thermophilin 9
L. monocytogenes
[40]
S. thermophilus CHCC3534
S. typhimurium, S. aureus
[41]
S. thermophilus B59671.
Thermophilin 110
Pediococcus acidilactic
[42]
XIV. S. thermophilus Against Bacterial Vaginosis
Bacterial vaginosis (BV) is the most common vaginal infection in reproductive aged women. This
infection occurs when predominantly anaerobic bacteria such as Gardnerella vaginalis, as well as Mycoplasma
hominis, Prevotella and Peptostreptococcus replace the dominant and normal Lactobacillus bacteria in the
vagina. One hundred twenty healthy Chinese women with a history or recurring bacterial vaginosis (BV) were
randomly assigned to a daily vaginal probiotic capsule as prophylaxis that contained 8 billion colony forming
units of Lactobacillus rhamnosus, L. acidophilus and S. thermophilus or a daily vaginal placebo capsule.
Women were to insert the capsule 7 days on, 7 days off and 7 days on. Probiotic prophylaxis resulted in lower
recurrence rates for BV (15.8% [9/57 women] vs 45.0% [27/60 women]; P < .001) and Gardnerella vaginalis
incidence through 2 months (3.5% [2/57 women] vs 18.3% [11/60 women]; P = .02). Between the 2- and 11-
month follow-up periods, women who received probiotics reported a lower incidence of BV and G vaginalis.
Aside from vaginal discharge and malodour, no adverse events were reported in either study group [43].
Table 4: Few Probiotic example activities of Streptococcus thermophilus
Probiotic Activity
Strain
Reference
Suppression of Ulcerative colitis
S. thermophilusST28, S.thermophilus ATCC 19258
[48]
Lactose digestion
S.thermophilus MUH 341
[49]
Decrease in blood pressure
S. thermophilusTMC 1542
[50]
Reduction in Blood cholesterol
S.thermophilus
[51]
Anti-gastric activities
S.thermophilus CRL 1190
[46]
Against Chronic gastritis
S.thermophilus CRL 1190
[45]
Anti-tumor activity
S.thermophilus
[53]
Anti-listerial activity
S.thermophilus
[54]
Food Preservative
S.thermophilus CCHC 3534
[55]
XV. Stable Growth In Children
Food supplements containing S thermophilus have been found to maintain a stable growth rate in
children. Children consuming S. thermophilus containing supplements had shown better growth during a 6-
month period than children who did not receive the supplement [44].
XVI. Biotherapeutic
S. thermophilus is found to be potentially therapeutic against the associated chronic gastritis (ASA)
[45] Gastritis is a common disorder in which discontinuity of the gastric mucosa is observed. It is caused by
various factors like excess alcohol, infection, intensive consumption of anti-inflammatory drugs with
Helicobacter pylori or may be stress. Also, ASA affects various mucosal defence lines such as bicarbonate
secretion, mucus synthesis, and decrease of mucosal blood flow. The first therapeutic effect of the fermented
milk with the polymer producing strain of S. thermophilus on chronic gastritis induced by ASA in mice. It was
able to generate immune response in mice and increased the thickness of the gastric mucus gel layer. Studies
suggest that recombinant lactic acid bacteria are the excellent candidates for the production of various bio
therapeutic proteins and also their delivery to specific places of requirement within the gastrointestinal tract [46,
47]
XVII. Conclusion
It is evident from several studies that, S. thermophilus has the potential to be majorly beneficial to
human health. Studies have already indicated many positive results stemming from S. thermophilus. As such
research moves forward, other findings are attracting attention of scientists, such as the suggestion that food
stuff containing such bacteria may have anti-carcinogenic cancer-fighting properties as well. For this reason,
promoting a superior understanding of human health as it relates to the adequate balance of bacteria in the body
is extremely important and warrants further research and investigation. Additionally, role of this bacterium is
continuously expanding from use in health maintenance and supplementation in the event of dysbiosis
(microfloral imbalance) during antibiotic therapy, to a wide range of health applications including skin ailments.
With the increase in knowledge and exploring other strains of importance, future trends envisage their increased
inclusion in dietary supplements and food stuff that target to a diverse preventive measure in health maintenance

Probiotic Efficacy and Potential of Streptococcus thermophilus modulating human health: A synoptic
www.iosrjournals.org 57 | Page
needs. Furthermore, there is considerable desideratum to establish the dose which is more effective and strains
required for optimal benefit either in a disease state, or as preventive Consequently, far more research is needed
before complete implementation but still probiotics seem to be a reliable method of treatment.
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