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The use of probiotics and safety concerns: A review


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Probiotics are defined as "live microorganisms which when administered in adequate amounts confer a health benefit on the host''. Most probiotics fall into the group of organisms' known as lactic acid-producing bacteria and are normally consumed in the form of yogurt, fermented milks, cereal or other fermented foods. Many of the products currently available in the market are not clearly tied to research documenting beneficial effects. Probiotics are regulated by FDA and several reports are available now for mislabeling the product claiming health benefits. As live microbial products, probiotics are potential sources of risk and there exists skeptical attitude among medical professionals and consumers who have less than optimal experiences with probiotics. This review outlines information regarding probiotics, overview of proposed regulatory guidelines and commercial probiotic products available in the market considered as safe for humans.
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African Journal of Microbiology Research Vol.6(41), pp. 6871-6877, 27 October, 2012
Available online at
DOI: 10.5897/AJMR12.1281
ISSN 1996-0808 ©2012 Academic Journals
The use of probiotics and safety concerns: A review
K Suresh Babu Naidu1*, Jamila K Adam1 and Patrick Govender2
1Department of Biomedical and Clinical Technology, Durban University of Technology, Durban-4000, South Africa.
2Department of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
Accepted 22 August, 2012
Probiotics are defined as live microorganisms which when administered in adequate amounts confer
a health benefit on the host’’. Most probiotics fall into the group of organisms’ known as lactic acid-
producing bacteria and are normally consumed in the form of yogurt, fermented milks, cereal or other
fermented foods. Many of the products currently available in the market are not clearly tied to research
documenting beneficial effects. Probiotics are regulated by FDA and several reports are available now
for mislabeling the product claiming health benefits. As live microbial products, probiotics are
potential sources of risk and there exists skeptical attitude among medical professionals and
consumers who have less than optimal experiences with probiotics. This review outlines information
regarding probiotics, overview of proposed regulatory guidelines and commercial probiotic products
available in the market considered as safe for humans.
Key words: Probiotics, health benefits, safety, dosage, applications.
The term 'probiotics' was derived from the Greek word,
meaning "for life" (Reid et al., 2003). An expert panel
commissioned by Food and Agriculture Organization
(FAO) and World Health Organization (WHO) defined
probiotic as "live micro-organisms," which, when
administered in adequate amounts confers a health
benefits on the host (FAO/WHO, 2006). Recently, there is
an increasing scientific and commercial interest in the
use of beneficial microorganisms for the prevention and
treatment of diseases (Figure 1). The use of microor-
ganisms to restore or maintain health is the basis of
probiotics which is one of the largest segments of the
functional foods (FF) market. The global sales of probiotic
supplements were predicted to rise 48% from $2.7bn in
2011 to $4bn in 2016 (
Consumer-Trends). In US, per capita spending on
probiotic supplements is expected to nearly double by
2016 and overtake Japan. Indeed, the market of
probiotics and healthy food has great potential to grow,
especially in Asia. However, the European market is now
saturated, and growth of probiotic market is likely to occur
mainly in non-dairy food areas and novel applications
*Corresponding author. E-mail: Tel:
+27-31-3735291. Fax: +27-31-3735255.
(Rivera-Espinoza and Gallardo-Navarro, 2010). The
different bacterial genera most commonly used in
probiotic preparations are Lactobacillus, Bifidobacterium,
Escherichia, Enterococcus, Bacillus, Streptococcus and
Pediococcus (Adam et al., 2012). Some fungal strains
belonging to Saccharomyces (Saccharomyces boulardii)
are now used as a ―drug‖ to prevent or treat recurrent
Clostridium difficile infection (CDI), particularly in critically
ill patients (Gupta and Garg, 2009; Mc Farland, 2009).
This review focuses on highlighting the current regulatory
framework, risks associated, dosage and probiotic
products currently available in the market for human
consumption for various treatments.
Occurrence and action of probiotics
Most existing probiotics have been isolated from the
human gut microbiota. This microbiota plays an important
role in human health, not only due to its participation in
the digestion process, but also for the function it plays in
the development of the gut and the immune system
(Sanchez et al., 2012). The human gastrointestinal (GI)
tract is home to a complex consortia of trillions
(approximately 1 × 1013 to 1 × 1014) of microbes,
thousands of bacterial phylotypes, as well as hydrogen-
consuming methanogenic archaea, colonizing the entire
6872 Afr. J. Microbiol. Res.
Figure 1. Health benefits of probiotics.
length of the gut with a collective genome (also termed as
microbiome) that contains at least 100-times as many
genes as our own genome (Cho and Blaser, 2012; Wei et
al., 2008). Cutting edge research and vast accumulating
data indicates that the gut microbiota is instrumental in
energy metabolism and immune function of the host, and
has a crucial role in the development of numerous
conditions including obesity (Clarke et al., 2012; Ley et
al., 2006) diabetes (Bergman et al., 2006), non-alcoholic
fatty liver disease (Dumas et al., 2006), inflammatory
bowel diseases (Quigley, 2012; Strober et al., 2008), and
cancer (Parvez et al., 2006). Mechanism of action of
probiotics is not completely understood, however as
general include 1) Adherence and colonization of gut, 2)
Suppression of growth of pathogenic bacteria, 3)
Production of antimicrobial compounds, 4) Improved
intestinal barrier function, 5) Stimulation of mucosal and
systemic host immunity, 6) Controlled transfer of dietary
antigens (Sharma et al., 2012).
Registering probiotic product
Regulatory issues are of prime focus for those involved in
the development and marketing of probiotic products.
The European Food Safety Authority (EFSA) recently
determined that none of the claims for specific probiotic
strains submitted to date were adequately substantiated
by the scientific data that were provided as evidence of
support (EFSA, 2009). Health Canada recently provided
industry guidance on probiotic-containing foods (http:
//www.hc-sc. and is developing guidance for
probiotic natural health products. The Indian Council of
Medical Research (ICMR) is developing guidelines for
India that would require probiotic strains to be backed by
clinical trials preferably conducted in local population, if
they are to be marketed (Gokhale and Nadkarni, 2007).
Recently, Shane et al. (2010) developed a guide for the
design of well performed, randomized, controlled clinical
studies in human participants in order to provide
acceptable evidence to support a probiotic claim.
Although the concept of probiotics is not new, the
advent of commercial products has refocused attention
on their potential uses and applications. However, in the
last few years new probiotic products have been
introduced onto the market, with the inevitable
competition for the consumers’ disposable income.
Additionally, the products have been introduced to health
care professionals with a variety of therapeutic claims for
health and benefit, often with extrapolated clinical
evidence of efficacy (Elliott and Teversham, 2004).
Probiotics in the United States could potentially be
regulated in a variety of different product range
depending on the intended use either as Conventional
foods (For consumption by general population), Dietary
supplements (A subcategory of foods, the dietary
supplement category was created in 1994 by the Dietary
Supplement Health and Education Act- the products are
meant to be used as oral supplements to the diet, and
are not to be represented as meals), Medical foods
(Foods used under medical supervision for patients
needing special dietary support for medical condition),
Feed additives (Termed "Direct fed microbials" by the
USDA) or as Drugs ( According to
the Food and Drug Administration (FDA) definition, a
drug is an article intended for use in the diagnosis, cure,
mitigation, treatment, or prevention of disease (FDA,
2009). If a probiotic is intended for use as a drug, then it
must undergo the regulatory process as a drug, which is
similar to that of any new therapeutic agent. Sanders
(2009), in effectively choosing a product by both health
care providers and consumers recommends that any new
Naidu et al. 6873
Figure 2. FAO/WHO Guidelines for the evaluation of probiotics for food use.
drug under investigation must be submitted and approved
by FDA as safe and effective before an investigational or
biological product can be administered to humans.
In an attempt to standardize the global requirements
needed to make health claims regarding probiotic agents,
the Joint Food and Agriculture Organization of the United
Nations/World Health Organization Expert Consultation
on Evaluation of Health and Nutritional Properties of
Probiotics developed guidelines for evaluating probiotics
in food that could lead to the substantiation of health
claims. The recommended evaluation of probiotics for
food use is shown in Figure 2. Consensus on uniform
regulations is desirable to ensure identity, quality
manufacturing processes, accurate labeling, proven
safety and efficacy for a product that will carry the label
Safety of probiotics
The absolute essence of Probiotics to be considered as
safe is the absence of pathogenicity and infectivity.
Safety criteria for successful probiotics have been well
defined in several studies (Forssten et al., 2011; Pineiro
and Stanton, 2007; Mattila and Saarela, 2000; Saarela et
al., 2000).
The fact to prove that the probiotic bacteria are
infective is difficult, especially in anaerobes, which are
generally considered to have no infectivity. Even if the
bacteria are administered orally, infection does not
normally occur in healthy animals; this is particularly so
for bacteria with weak infectivity. Even with strongly
infective bacteria, it is not easy to establish infection by
using a single species, and various techniques are
necessary to establish infection, such as the use of
various pre-treatments in the experimental system or the
use of mixed infection. Adverse effects of probiotics, if
they occur, are usually mild and affect the digestive
system in children (e.g., abdominal discomfort or
flatulence) with short gut syndrome (Oliver and Reid,
2009; Kligler et al., 2007). However, as viable and potent
microorganisms, probiotics have the potential to cause
invasive infections in hosts who may have compromised
mucosal epithelia. Invasive infections have primarily been
noted to occur in immunocompromised adults. It is
advisable to avoid probiotics in these patients or to be
aware of risk of sepsis.
Lactobacillus species are a rare but well-recognized
cause of endocarditis in adults (and other forms of sepsis
in children) in the absence of probiotic supplementation.
Several reports have directly linked cases of
Lactobacillus and other bacterial sepsis to the ingestion
of probiotic supplements. The reader is suggested to
consult Boyle et al. (2006) for in-depth review of this
subject. A proposed scheme for safety assessment of
probiotics is presented in Table 1. Most stringent studies
have to be completed for genetically modified strains
intended for human consumption before
commercialization (Choi et al., 2012; Sorokulova, 2008;
Salminen et al., 1996).
6874 Afr. J. Microbiol. Res.
Table 1. Important studies for safety assessment of probiotic lactic acid bacteria (LAB) and other bacteria (Donohue and Salminen, 1996).
Type of property studied
Safety factor to be assessed
Intrinsic properties of lactic acid
Adhesion factors, antibiotics resistance, existence of plasmids and Tra genes, harmful enzyme
Metabolic products
Concentrations, safety and other effects
Toxicity studies
Acute and subacute effects of ingestion of large amounts of tested bacteria
Mucosal effects
Adhesion, invasion potential, intestinal mucus degradation, infectivity in immunocompromised
Dose response effects
Dose response studies by oral administration in volunteers
Clinical assessment
Potential for side effects, careful evaluation in healthy volunteers and disease specific studies
Epidemiological studies
Surveillance of large populations following introduction of new strains and products
Table 2. Probiotic preparations.
Probiotic strain
Recommended daily dosage
rhamnosus GG
10 billion CFUs
Capsules (Culturelle) Therapeutic yogurts and fermented milks
Lactobacillus sp./
Bifidobacterium sp
100 million to 35 billion CFUs,
depending on preparation
Capsules (Align, Primadophilus) Powder (Primal Defense) Capsules or powder (Fem-Dophilus,
Jarro-Dophilus) Therapeutic yogurts and fermented milks (Activia, Danactive, Yo-Plus)
Saccharomyces Boulardii
250 mg to 500 mg
Capsules (Florastor)
Bacillus sp
107-108 spores g-1
Powder (Bibactyl)
a CFU= colony-forming unit, b Most commercial brands contain a mixture of strains that may include Lactobacillus acidophilus, L. rhamnosus,
Lactobacillus bulgaricus, Bifidobacterium bifidum, Bifidobacterium longum, and others. Exact combinations of strains vary among brands
The right dosage
Probiotics are generally sold as capsules, powder,
tablets, liquid, or are incorporated into food. The specific
number of colony forming unit (CFUs) contained in a
given dose or serving of food can vary between brands
(Kligler and Cohrssen, 2008). Patients should be advised
to read products label carefully to make sure that they are
getting the right dose. Interestingly, probiotics are
available over the counter and are not regulated by FDA
but generally regarded as safe. Because probiotics are
not regulated by the FDA, there are no standard dosage
recommendations for probiotics. Providers typically use
half the adult dose for pediatric patients and a one-fourth
dose for infants (Cabana et al., 2006). A recent study
analyzed a range of brands of probiotics and found that
of the 19 brands examined, five did not contain the
number of live microorganisms stated on the label
Because some labels are unreliable, physicians should
recommend specific brands known to be of reasonable
quality or encourage patients to research brands before
purchasing a specific product. Guidance on probiotics
can be found at and at the
National Center for Complementary and Alternative
Medicine’s Web site, http://
Presently, a wide range of dosages for Lactobacillus
sp. and other probiotics have been studied in clinical
trials and are available, ranging from 100 million to 1.8
trillion CFUs per day, with larger dosages used to reduce
the risk of pouchitis relapse. Most studies examined
dosages in the range of 1 to 20 billion CFUs per day,
although exact dosages for specific indications varied
within this range. Generally, higher dosages of probiotics
(that is, more than 5 billion CFUs per day in children and
more than 10 billion CFUs per day in adults) were
associated with a more significant study outcome. The
dosages of S. boulardii in most studies range between
250 and 500 mg per day (Table 2).
Probiotic products
Fermented dairy products enriched with probiotic bacteria
have developed into one of the most successful
Naidu et al. 6875
Table 3. Commercial probiotic products in market (Cutting, 2011; Suvarna and Boby, 2005)*.
Nestle, India
Gut Probiotic
Unichem, India
Gastrointestinal Health
Bacillus mesentricus, Clostridium butyricum,
Streptococcus faecalis, Lactobacillus sporogenes
Lamb Performance
Vetcare India Pvt. Ltd, India
Vaginal Infections, Gastrointestinal health
Saccharomyces cerevasie, lactobacillus
Cadila, India
Vaginal infections
Glenmark, India
Gastrointestinal health
Lactobacillus acidophilus,
Amul, India
Streptococcus faecalis, Clostridium butyricum,
Bacillus mesentricus LAB
Ranbaxy, India
Antibiotic associated Diarrhoea (AAD)
Lactobacillus casei DN 014001
Danone, France
Immune booster
Lactobacillus casei
Yakult Honsha Co., Ltd, Japan
Gastrointestinal health
Lactobacillus plantarum
Probi, Lund
Gastrointestinal health
Lactobacillus GG
Valio Ltd, Finland
Gastrointestinal health
JPC, Clostridium butyricum, Bacillus mesentricus,
Lactobacillus sporogenes
Tablets India Pvt Ltd, India
Irritable bowel syndrome, Diarrhoea.
Lactobacillus johnsonii
Gastrointestinal health
Bifidobacterium infantis, Bifidobacterium longum,
Bifidobacterium bifidum
Arise & Shine Herbal Products Inc, USA
Gastrointestinal health
Bacillus subtilis
Bacillus licheniformis
Biofarm, Dniepropetrovsk, Ukraine
Garars, Russia
Pyo-speticpost operational complications, bacterial vaginitis,
Bacillus clausii
Sanofi Winthrop SpA, Milan, Italy
Bacteriotherapy and bacterioprphylaxis of gastrointestinal disorders
Microbial Solutions, Johannesburg, South Africa
6876 Afr. J. Microbiol. Res.
Table 3. count
Labeled as Lactobacillus sporogenesbut contains
Bacillus coagulans
Pharmed Medicare, Bangalore, India
Gastrointestinal health
Saccharomyces boulardii
Biocodex, USA
Gastrointestinal Health
Streptococcus thermophilus 1131
Meiji milk products, Tokyo
Gastrointestinal health
Lactobacillus reuteri SD2112
BioGaia, North Carolina
Gastrointestinal health
Lactobacillus acidophilus NCFM
Rhodia, Madison
Gastrointestinal health
Lactobacillus acidophilus
Akacia Health Care (Pty) Ltd, South Africa
Immune booster
Bifidobacterium longum BB536
Morinaga Milk Industry Co., Ltd., Japan
Gastrointestinal health
Enterococcus, Pediococcus, Lactobacillus,
Biomin, Herzogenburg, Austria
Improved weight gain, decreased mortality, inhibition of enteric pathogens
Pediococcus acidilactici, Saccharomyces boulardii
Imagilin Technology, USA
Supports digestive system, Reduces stress, Reduces diarrhea, Reduces vomiting,
Relieves constipation, Decreases body odor, Enhances immune response
*partial list
categories of functional foods. They gave rise to
the creation of a completely new category of
probiotic products like the daily-dose drinks in
small bottles, yoghurt, ice creams, milk based
desserts, powdered milk for infants, butter,
mayonnaise, cheese, products in the form of
capsules or fermented food of vegetable origin.
Although there are several dozen products in the
market that claim to have probiotic activity
representatives of only a handful of species
dominate the market or have been used in
multiple clinical trials. Some of them are listed in
Table 3. These include strains of L. casei, L.
johnsonii, L. rhamnosus and L. plantarum, which
are all of human origin and are known under
defined brand names. It has been estimated that
there were approximately 70 probiotic-containing
products marketed in the world (Shah, 2004), and
the list is continuously expanding.
Moreover, probiotic products containing Bacillus
species have been in the market for at least 50
years with the Italian product known as
Enterogermina® registered in 1958 in Italy as an
OTC medicinal supplement (Cutting, 2011). Of the
species that have been most extensively
examined are B. subtilis, B. clausii, B. cereus, B.
coagulans and B. licheniformis. Spores that are
being heat-stable have a number of advantages
over other non-spore formers such as
Lactobacillus spp., namely, that the product can
be stored at room temperature in a desiccated
form without any deleterious effect on viability. A
second advantage is that the spore is capable of
surviving the low pH of the gastric barrier
(Spinosa et al., 2000; Barbosa et al., 2005) which
is a limitation for all species of Lactobacillus
(Tuohy et al., 2007).
Probiotics are foods that contain live
These microorganisms on metabolite production
will give these probiotics their health promoting
properties such as boosting immune system,
prevent allergies, stop eczema and heal the
intestine. Presently the scientific community is at
the crossroads, firstly in determining whether
probiotics are safe and effective in the treatment
of many conditions for which they are already in
use. This necessitates addressing basic issues
such as dosing, safety and mechanisms of actions
of these agents. Other major concern about
probiotics is prior use for human consumption
alone is insufficient to support clinical studies for
registering if this does not match intended use as
drug. Finally there exist very few large scale, long
term clinical trials conducted on probiotics to
support them as ―drug‖. However, available data
from medical literature and clinical studies clearly
indicate that probiotics have great health potential
particularly to overcome threat of use of antibiotic
over dose and prevalence of antibiotic resistant
microorganisms. The future probiotic research should
essentially focus and provide more precise information on
mechanisms by which probiotics exert their beneficial
effects in vivo in various gastrointestinal related diseases
and greater acceptance by the medical community.
We extend our sincere acknowledgement to Prof S Mayo,
Research Management Division, Durban University of
Technology, South Africa for awarding Post Doctoral
fellowship to Dr. K. Suresh Babu Naidu.
Adam JK, Bharti O, Naidu KSB (2012). Probiotics: Recent
understandings and biomedical applications. Curr trends in
Biotechnol.Pharma. 6:1-14.
Barbosa TM, Serra CR, La Ragione RM, Woodward MJ, Henriques, AO
(2005). Screening for Bacillus isolates in the broiler gastrointestinal
tract. Appl.Environ.Microbiol. 71:968-978.
Bergman AJ, Stevens C, Zhou Y (2006). Pharmacokinetic and
pharmacodynamic properties of multiple oral doses of stigliptin, a
dipeptidyl peptidase-IV inhibitor: a double blind, randomized,
placebo-controlled study in healthy male volunteers. Clin. Ther.
Boyle RJ, Robins-Browne RM, Tang MLK (2006). Probiotic use in
Clinical practice. What are the risks. Am. J. Clin. Nutr. 83:1256-1264.
Cabana MD, Shane AL, Chao C, Hemker MO (2006). Probiotics in
primary care pediatrics. Clin.Pediatr. 45:405-410.
Cho I, Blaser MJ (2012). The human microbiome: at the interface of
health and disease. Nature.Rev. Gene. 13:260-270
Choi HJ, Ahn JH, Park SH, Do KH, Kim J, Moon Y (2012). Enhanced
Wound Healing by Recombinant Escherichia coli Nissle 1917 via
Human Epidermal Growth Factor Receptor in Human Intestinal
Epithelial Cells: Therapeutic Implication Using Recombinant
Probiotics. Infect Immunol. 80:1079-1087
Clarke S, Murphy E, Nilaweera E, Ross P, Shanahan F, O’T oole PW,
Cotter PD (2012). The gut microbiota and its relationship to diet and
obesity: New insights. Gut Microbes. 3:1-17
Cutting SM (2011). Bacillus probiotics. Food Microbiol. 28:214-220
Dumas ME, Barton RH, Toye A (2006). Metabolic profiling reveals a
contribution of gut microbiota to fatty liver phenotype in insulin-
resistant mice. PNAS. 103:12511-12516.
European Food Safety Authority (2009). Briefing document for Member
States and European Commission on the evaluation of Article 13.1
health claims. Parma, Italy, 11 November 2009; EFSA J. 7:1386
Elliott E, Teversham K (2004). An evaluation of nine probiotics available
in South Africa, August 2003. South Afr. Med. J. 94:121-124
FAO/WHO (2006). Probiotic in foods. Health and nutritional properties
and guidelines for evaluation. In FAO Food and Nutrition; 2006 pp 85
ISBN 92-5-105513-0. Also available at
Food and Drug Administration (2009). Development andapproval
process (drugs) [updated 2009 Oct 14; cited 2010 Jun
Forssten SD, Sindelar CW, Ouwehand AC (2011). Probiotics from an
industrial perspective. Anaerobe.17:410-413.
Gokhale G, Nadkarni A (2007). Probiotic foods market in India soon to
be regulated. India Law Journal, 2007, Accessible via
Gupta V, Garg R (2009). Probiotics. Ind J. Med. Microbiol. 27:202-209.
Health Canada. Guidance DocumentThe Use of Probiotic
Microorganisms in Food 2009, Food Directorate, Health Products and
Naidu et al. 6877
Food Branch, Health Canada, April 2009. Accessible via http://www.hc-
Kligler B, Hanaway P, Cohrssen A (2007). Probiotics in children. Ped.
Clin. N. Am. 54:949-967.
Kligler B, Cohrssen A (2008). Probiotics. Amer fam Phys., 78: 1073-
Ley RE, Peter J, Turnbaugh, Klein S, Gordon JI (2006). Microbial
ecology: Human gut microbes associated with obesity. Nature.
Mattila T, Saarela M (2000). Probiotic functional foods. In: Williams MC,
Gibson RG, editors. Functional foods. Washington, DC. Boca Raton:
CRC Press LLC. pp. 287-313
Mc Farland LV (2009). Evidence-based review of probiotics for
antibiotic-associated diarrhea and Clostridium difficile infections.
Anaerobe 15:274-280.
Oliver MM, Reid V (2009). Use of probiotics in Child care. J Ped Health
Care. 23:194-197.
Parvez S, Malik A, Kang S Ah, Kim HY (2006). Probiotics and their
fermented food products are beneficial for health. J. Appl.
Pineiro M, Stanton C (2007). Probiotic bacteria: legislative framework e
requirements to evidence basis. J.Nutri. 137:850S-853S.
Quigley EMM (2012). The use of probiotics, prebiotics and synbiotics in
the management of irritable bowel syndrome. Eur Gastr.Hepat.Rev.
4:233-236. DOI: 10.1111/j.1574-6968.2012.02593.x
Reid G, Jass J, Sebulsky MT, McCormick JK (2003). Potential use of
probiotics in clinical practice. Clin Microbiol Rev. 16: 658-672.
Rivera-Espinoza Y, Gallardo-Navarro Y (2010). Non-dairy probiotic
products. Food. Microbiol. 27:1-11.
Saarela M, Mogensen G, Fondén R, Mättö J, Mattila-Sandholm T
(2000). Probiotic bacteria: safety, functional and technological
properties.J. Biotechnol. 84:197-215
Salminen S, Isolauri E, Salminen E (1996). Clinical uses of probiotics
for stabilizing the gut mucosal barrier: successful strains and future
challenges. Antonie Van Leeuwenhoek. 70:347-358.
Sanchez B, Ruiz L, Gueimonde M, Madiedo PR, Margolles A (2012).
Toward improving technological and functional properties of
probiotics in foods, Trends in Food Science & Technology.,
Sanders ME (2009). How do we know when something called
―probiotic‖ is really a probiotic? A guideline for c onsumers and health
care professionals. Functional. Food. Rev. 1:B312.
Sharma S, Agarwal N, Verma P (2012). Probiotics: The Emissaries of
Health from Microbial World. J. Appl. Pharm. Sci. 2:138-143
Shah NP (2004). Probiotics and prebiotics. Agro-Food. Indust. Hi-tech.
Shane AL,Cabana MD, Vidry S, Merenstein D,Hummelen R,Ellis
CL,Heimbach JT, Hempel S, Lynch SV, Sanders ME, Tancredi DJ
(2010). Guide to designing, conducting, publishing and
communicating results of clinical studies involving probiotic
applications in human participants. Gut Microbes 1:243-253
Spinosa MR, Braccini T, Ricca E, De Felice M, Morelli L, Pozzi G,
Oggioni MR (2000). On the fate of ingested Bacillus spores. Res.
Microbiol. 151:361-368
Sorokulova I (2008). Preclinical Testing in the Development of
Probiotics: A Regulatory Perspective with Bacillus Strains as an
Example. Clin. Infec. Dis. 46:92-95
Strober W, Fuss I, Mannon P (2007). The fundamental basis of
inflammatory bowel disease. J. Clin. Invest. 17:514-521.
Suvarna VC, Boby VU (2005). Probiotics in human health: a current
assessment. Curr. Sci. 88: 1744-1748
Tuohy KM, Pinart-Gilberga M, Jones M, Hoyles L, McCartney AL,
Gibson GR (2007). Survivability of a probiotic Lactobacillus casei in
the gastrointestinal tract of healthy human volunteers and its impact
on the faecal microflora. J.Appl.Microbiol. 102:1026-1032
Wei J, HoukaiLi, Liping Zhao, Jeremy Nicholson K (2008). Drug
targeting, Nature Reviews Drug Discovery.7: 123-131.
... Administration of psychobiotics (probiotics) or prebiotics and paraprobiotics is known to improve neurodegenerative diseases by modulating the gut microflora and immune responses. Considering the safety concerns of live microbial probiotics (Naidu et al., 2012;Salminen et al., 2021), the interest in non-viable microorganisms or microbial cell extracts has been burgeoning. For instance, the anxiolyticand antidepressant-like effects of heat-killed Enterococcus faecalis and Lactobacillus paracasei PS23 were reported to be mediated via the expression of Adrb3 and Avpr1a genes in the prefrontal cortex or brain-derived neurotrophic factor, mineralocorticoid, and glucocorticoid receptor in the hippocampus (Kambe et al., 2020;Wei et al., 2019). ...
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Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are major age-related concerns in elderly people. Since no drug fully addresses the progression of neurodegenerative diseases, advance treatment strategies are urgently needed. Several studies have noted the senescence of immune system and the perturbation of gut microbiota in the aged population. In recent years, the role of gut microbiota has been increasingly studied in the manifestation of age-related CNS disorders. In this context, prebiotics, probiotics, and paraprobiotics are reported to improve the behavioural and neurobiological abnormalities in elderly patients. As live microbiota, prescribed in the form of probiotics, shows some adverse effects like sepsis, translocation, and horizontal gene transfer, paraprobiotics could be a possible alternative strategy in designing microbiome-based therapeutics. This review describes the health-beneficial effects of paraprobiotics in age-associated neurodegenerative diseases.
... accounting for up to 90% of their weight (Warshakoon et al., 2009) and is an essential polymer in lactobacilli that determines the shape and preserves their integrity (Sengupta et al., 2013). PGN is an indispensable molecule of LAB and is suggested to be important for the functionalities of a probiotic bacterium (K, Jamila et al., 2012). Studies has also found that Lactobacillus strain-specific antiinflammatory capacities are somehow correlated with the PGN structure (Fernandez et al., 2011). ...
The human intestinal microbiota is composed of several types of microorganisms, including bacteria, archaea, fungi, unicellular eukaryotes and viruses. Among them, bacteria are the most diverse and abundant with a gene catalog 150 times larger than the genes present in the human genome, which represents a tremendous metabolic potential. These bacteria actively participate in the maintenance of intestinal homeostasis. Dysbiosis of the gut microbiota could be observed at course of many human pathologies, particularly inflammatory diseases intestinal chronic diseases (IBD), such as Crohn's disease (CD) or Ulcerative colitis (UC). These dysbiosis could contribute to the onset and progression of diseases. For example, gut microbiota transplantation experiments in murine model have allowed to show that a dysbiotic microbiota is sufficient to induce chronic inflammation in the colon and thus lead to the development of a metabolic syndrome or colitis. Different intervention strategies, including fecal transplantation, administration of probiotics or even special nutritional diets have been developed to act on the microbial communities of the digestive tract and to restore homeostasis of host tissues. The success of some interventions like Fecal transplantation represent a proof of concept in humans that acting on the composition of the intestinal microbiota is a strong lever to resolve certain physio pathological situations associated with gut microbiota dysbiosis. Diet is another important method for modulating the gut microbiota since it is the most important factor influencing its composition. In fact, the nutrients ingested can act directly on the composition of the microbiota by serving as substrates for microorganisms and indirectly by modulating intestinal homeostasis and components of the immune system associated, themselves contributing to regulate the composition microbiota. It is expected that ingestion of these beneficial microorga nisms can stimulate the immune system, promote intestinal homeostasis and to some extent contribute to the balance of the microbiota intestinal. The use of probiotic microorganisms is found to be very effective in some studies to treat different physiopathological situations (colitis, metabolic syndrome) in laboratory model organisms (rats, mice), however the use of these same probiotics in humans have given relatively disappointing clinical results, with poorly reproducible results across cohorts of patients. Except for the treatment of antibiotic-associated diarrhea. These discrepancies in results between pre-clinical models and clinical trials encourage better characterization of the molecular mechanisms used by probiotics to exert their beneficial effects and especially better understand the relationship of these probiotic microorganisms with the resident microbiota and diet.Among the different rising intervention strategies practiced nowadays in the purpose to shape the microbiota, a growing interest is given to other dietary interventions, like caloric restriction (CR) which has demonstrated several beneficial effects on various physiological systems, including the gastro-intestinal system, by modulating the innate and adaptative immune responses. In fact, emerging evidence suggests that the immune system function might be heavily influenced by the sensing of nutrient, reinforcing the idea that diet can deeply influence the inflammatory responses.
... The International Dairy Federation suggests that probiotic products must contain at least 10 6 viable probiotic bacteria per gram or milliliter of product at the time of consumption to exert beneficial effect on the host's health (Roy, 2005), some authors recommend daily doses of 10 6 -10 7 CFU of viable cells per gram or milliliter of product (Martins et al., 2016), whereas other authors recommend a greater number of about 10 9 -10 10 CFU of viable cells per gram or milliliter (Naidu, Adam, & Govender, 2012). Thus, the mixed mango and carrot juices processed by HIP or pasteurized can be considered as promising vehicles to carry L. plantarum, since they presented counts above 10 8 CFU/ml of viable cells throughout storage period. ...
This study aimed to elaborate a mixed mango and carrot juice processed thermally and by high isostatic pressure (HIP) added L. plantarum. L. plantarum caused a decrease in pH and increase in acidity of the juices, but did not change the antioxidant capacity (AC), and α‐ and β‐carotene contents. HIP maintained the microbiological quality, whereas the pasteurized juices showed high psychrotrophic counts after 35 storage days. HIP did not influence the AC, whereas the pasteurized juices showed a decrease in AC and a 30% reduction in carotenoid contents. Pasteurization reduced the polyphenoloxidase and peroxidase activities and HIP promoted a reduction in polyphenoloxidase activity but increased the peroxidase activity (~30%). Mixed juices presented good sensory acceptance (HIP juice showed the highest score). Thus, HIP showed to be more effective than thermal process, the matrix proved to be capable of maintaining the L. plantarum viability, and could be an alternative for dairy products. The results showed that the production of the probiotics mixed juices processed by high pressure is industrially interesting, since this process was able to better preserve sensory and nutritional characteristics of the juices compared to the thermal process. In addition, this probiotic product emerges as an alternative for vegetarian’s individuals who have diets with cholesterol restriction or allergy and/or intolerance to dairy products. Furthermore, due the effectiveness of applied conservation processes and biopreservation, these products were safe for consumption during the assessed refrigerated storage period.
... There was a reduction of approximately 1.5 log cycles in the L. plantarum LP299v count when compared to L. rhamnosus GG (p > 0.05) at 60 and 90 days of storage of the appetizer and, despite a reduction of the count, the appetizer still is a good carrier of this strain, since it showed counts above 10 7 CFU/g. Some authors consider that the level of probiotic cultures in food should be high, being in the range of 10 6 -10 8 CFU/mL (Hussain, Patil, Yadav, Singh, & Singh, 2016), while others suggest between 10 9 and 10 10 CFU/g (Martins, Ramos, Martins, & Rodrigues, 2015;Naidu, Adam, & Govender, 2012). ...
This study evaluated the viability of Lactobacillus plantarum LP299v or Lactobacillus rhamnosus GG in vegetable appetizer, as well as the resistance of the strains to the gastrointestinal tract (GIT) simulated in vitro. Control appetizer and added of probiotic strains were prepared and remained at 8 °C for 90 days. There was no difference in the L* and b* between the treatments and throughout the storage time. The control appetizer presented higher pH and lower acidity compared to probiotic appetizer. Vegetable appetizer showed counts of L. plantarum or L. rhamnosus higher than 7.42 Log CFU/g and 8.84 Log CFU/g respectively, along the refrigerated storage, being verified greater viability for L. rhamnosus (p < 0.05) with no reduction in the counts of both microorganisms over time (p > 0.05). Mean scores above 6.0 (“slightly appreciated”) were attributed to sensory analysis. The appetizer containing L. rhamnosus had a higher preference among consumers. In the in vitro GIT test, considering the consumption of a 100 g portion, in the time 90 days, approximately 8.67 Log CFU/g and 9.53 Log CFU/g of L. plantarum or of L. rhamnosus respectively, would be available to promote consumer benefits, which makes the appetizer apt to be considered probiotics.
... Viability of the probiotic cultures in the tropical mango juice L. rhamnosus GG and L. plantarum LP299v presented counts higher than 7.96 log CFU mL -1 and 7.74 log CFU mL -1 , respectively, throughout the 28 days of storage of the juices at 8 °C, showing no difference (p>0.05) in the viability of these cultures with time ( Figure 1). Although there is no consensus on the minimum amount of probiotic microorganisms needed to provide beneficial effects to the organism (MARTINS et al., 2016), some authors consider a value of >6 log CFU g -1 or mL -1 of the food (HUSSAIN et al., 2016), whilst others consider between 6 and 7 log CFU g -1 (MADUREIRA et al., 2011), or 9 to 10 log CFU g -1 (NAIDU et al., 2012). A 100 mL portion of the tropical mango juice containing L. rhamnosus or L. plantarum carried at least 9.96 log CFU or 9.74 log CFU of these microorganisms, sufficient to promote health benefits to the host. ...
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This study evaluated the viability of Lactobacillus acidophilus La-05, Lactobacillus plantarum LP299v and Lactobacillus rhamnosus GG in tropical mango juice, the resistance of the strains to gastrointestinal conditions simulated in vitro and the microbiological, physicochemical and sensory characteristics of the products obtained. The viabilities of L. rhamnosus GG and L. plantarum LP299v were greater than 7.96 log CFU mL ⁻¹ and 7.74 log CFU mL ⁻¹ , respectively, during the 28 days of storage at 8 °C. However, there was a reduction (p < 0.05) in the viability of L. acidophilus La-5 after 21 days of storage, with counts of 3.81 log UFC mL ⁻¹ . The parameters of pH, total soluble solids, luminosity (L ∗ ) and the color coordinates, a ∗ and b ∗ , did not differ between the treatments. However, the pH and acidity varied during the storage time, probably due to the fermentative action of the microorganisms. For the in vitro gastrointestinal resistance test, there was a difference in the gastric phase for enteric phases I and II. The mean viability of the microorganisms in the gastric phase was 5.11 log CFU mL ⁻¹ , decreasing to 4.02 and 3.97 log CFU mL ⁻¹ in enteric phases I and II, respectively. Juices containing L. rhamnosus GG and L. plantarum LP299 were evaluated sensorially, presenting good acceptability. The results suggest that the tropical mango juice was a good carrier matrix for L. rhamnosus GG and L. plantarum LP 299v, being well accepted and therefore an alternative for populations with dietary restrictions.
... The LGG presented counts above 7.2 log CFU/mL throughout the 28 days of storage of the juice at 8°C (Fig. 1) and in the non-LGG inoculated juice (negative control), the count of lactic acid bacteria were < 1.0 log CFU/mL. Although consensus does not exist concerning the minimum amount of probiotic microorganisms necessary to provide beneficial effects for the organism (Martins et al., 2016), some authors consider that one needs > 10 6 CFU/g or mL of food (Hussain, Patil, Yadav, Singh, & Singh, 2016), whereas others suggest between 10 6 and 10 7 CFU/g (Madureira, Amorim, Gomes, Pintado, & Macata, 2011), or even 10 9 to 10 10 CFU/g (Naidu, Adam, & Govender, 2012). The ingestion of 100 mL/day of the jussara plus pineapple juice fermented with LGG provides the consumer with a minimum of 9.2 log CFU/day, and hence the juice developed is a promising vehicle for LGG. ...
This study evaluated the viability of Lactobacillus rhamnosus GG (LGG) and its in vitro and in vivo resistance to the gastrointestinal tract (GIT) when carried by a mixed fermented pineapple and jussara juice. The effects of product ingestion on the biochemical characteristics of the blood and on the development of aberrant crypt foci (ACF) in Wistar rats were also determined. The LGG viability in probiotic juice was higher than 7.2 log CFU/mL throughout 28 days at 8 °C. The mean count of the probiotic microorganism in the fecal samples of the rats was 5.6 log CFU/g, identical to the count at the end of the in vitro trial (enteric phase II), indicating that the mixed pineapple and jussara juice was an excellent vehicle for LGG. No difference (p >.05) was verified to ACF among the groups. However, the results for the probiotic culture viability and its in vitro and in vivo resistance to the gastrointestinal tract suggest that this juice is an excellent carrier matrix for LGG and contributed to a reduction in the levels of the LDL (low density lipoprotein) fraction of the blood cholesterol, thus being an aid in the control of coronary diseases.
The health-promoting effects of probiotics are species-specific, and hence it is important to declare the correct information in products. However, some studies have identified issues related to the accuracy of labeling commercial probiotic products. In this study, we developed a high-resolution real-time PCR method based on pangenome analysis for a more affordable, rapid, and accurate identification of commercial probiotic products than sequencing methods. We selected 25 species or subspecies primarily used for probiotic strains and are closely related to them as targets. To extract molecular markers, 354 whole-genome sequences present in the target genomes but not in the pangenome of other genomes were compared, which resulted in the identification of molecular marker genes. The marker genes exhibited 100% specificity for 100 strains as assessed by the real-time PCR method. Fifty probiotic and dairy products were investigated to verify the information claimed on the label. Real-time PCR results showed that most products reflected the bacterial species declared in the label claim, whereas 12 products showed the presence of undeclared species or missing species. Our method for accurately verifying the labeling of probiotic products would be useful for quality control and safety.
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Probiotics is said to be the next most important immune defence system following antibiotic resistance. The Global Burden of Disease 2016 , reported that oral diseases affect around half of the population of the world (3.58 billion people) and dental caries are among the world's highest prevalence of diseases. Probiotics have shown promising results in the management of various systemic and oral diseases. The use of probiotics for management of dental caries is a rapidly emerging concept. This book aims to give a brief overview of the aspects of probiotics and the current evidence of use of probiotics in dental caries.
The resistance of Lactobacillus rhamnosus GG (LGG) to in vitro gastrointestinal digestion in mixed beverages (MB) prepared with legumes, peanut (MBPP) or soybean (MBSP), containing guava pulp and beet was evaluated, as well as the physical-chemical, microbiological and sensorial characteristics of these products. For this purpose, 4 beverages (MBPP and MBSP with probiotic and MBPC and MBSC as a control, without probiotic) were prepared. MBPP and MBSP was fermented and maintained together with their controls at 8 °C for 42 days. In the in vitro test of gastrointestinal resistance, for 100 mL of beverage ∼8.34 and 7.50 Log CFU/mL of LGG were available after digestion in BMPP and BMSP, respectively, which makes these products potential probiotics. The viability of LGG was >7.3 Log CFU/mL throughout storage in the beverages, which were microbiologically safe for consumption. The beverages containing LGG showed higher acidity and lower pH after processing compared to those without fermentation. Soybean beverages showed higher protein content (p < 0.05) compared to peanut beverages, which did, however, have higher lipids. After processing, the products showed hedonic scores equivalent to “I liked it a little” and “I liked it a lot”, which suggested a willingness to consume the product, thus possibly being viable non-dairy beverages.
Background: Despite the growing importance of probiotics vivid health benefits, an impediment to the use of new probiotic cultures is their safety. Hence, there is a need to strictly examine the biosafety as well as health benefits of probiotics in vivo model system. Results: In this study, two lactic acid bacterial (LAB) cultures Lactobacillus fermentum NCMR 2826 and FIX proven for their in vitro probiotic properties were investigated for their in vivo safety in Wistar rats. Acute toxicity study (14 days) with high dose of biomass (1016 CFU/mL), followed by sub-chronic test for 13 weeks with oral feeding of the probiotic cultures in three different doses viz; 10,7 108 and 1010 CFU/mL on daily basis revealed the safety of the L. fermentum cultures. The probiotic feeding had no toxic effects on the survival, body weight, food consumption, with either of the dosage used throughout the treatment period. No statistically significant changes in relative organ weight, serum biochemical and hematological indices were found among the control and the probiotic fed animals. In addition to the safety attributes, the two L. fermentum cultures fed rats showed reduced serum cholesterol levels, macrovesicular steatosis and hepatocyte ballooning compared to control animals. Further, quantification of intestinal microbiota using real-time PCR analysis from animal feces indicated a significant increase and stability of Lactobacillus and bifidobacterial counts but a decrease of E. coli numbers. Conclusion: This study of safety and beneficial features highlight the use of the two native L. fermentum isolates as potential probiotic food supplements. This article is protected by copyright. All rights reserved.
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Microbial cultures have been used for thousands of years in food and alcoholic fermentations, and in the past century have undergone scientific scrutiny for their ability to prevent and cure a variety of diseases. This has led to the coining of the term probiotics. Today probiotics are available in a variety of food products and supplements, and have got wide applications in the control of cholestrol, cancers, allergies, etc. This article discusses the summary of research on the health benefits of probiotics and offers practical information to help health professionals and even the layman.
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Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain.
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Probiotics are defined as “microbial food supplements” with beneficial effects on the consumers. Several aspects including safety, functional and technological characteristics, have to be taken into consideration in the selection process of probiotic microorganisms. Our Knowledge about probiotics and their interactions with the host has grown ever since Metchnikoff’s theory of longevity and proven mechanism of action on probiotics published elsewhere in medical literature. Certainly, now there is enough clinical evidence to support claimed health attributes to selected strains of Lactobacillus and Bifidobacterium spp. The aim of this review article is to summarise selection criteria of probiotics, technological challenges for probiotic formulations, safety assessment and potential applications of probiotics for health care professionals and common man
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Probiotics have a long history of human use and are traditionally consumed in several parts of the world. These are live microbes that can be formulated into many different types of products, including foods, drugs, and dietary supplements. Examples of foods containing probiotics are yogurt, fermented and unfermented milk, miso, tempeh, and some juices and soy beverages. Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also fit the bill. Probiotics are also called "friendly bacteria" or "good bacteria". They are gaining importance because of the innumerable benefits, e.g. treating lactose intolerance, hypercholesterolemia and managing cardiac problems like atherosclerosis and arteriosclerosis. With the current focus on disease prevention and the quest for optimal health at all ages, the probiotics potential could reign high. Health professionals and pharmaceutical companies need to objectively help and guide their clients and consumers toward appropriate prophylactic and therapeutic uses of probiotics that deliver the desired beneficial health effects, shunning type and instant benefits.
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The gastrointestinal mucosa has a remarkable ability to repair damage with the support of epidermal growth factor (EGF), which stimulates epithelial migration and proliferative reepithelialization. For the treatment of mucosal injuries, it is important to develop efficient methods for the localized delivery of mucoactive biotherapeutics. The basic idea in the present study came from the assumption that an intestinal probiotic vehicle can carry and deliver key recombinant medicinal proteins to the injured epithelial target in patients with intestinal ulcerative diseases, including inflammatory bowel disease. The study was focused on the use of the safe probiotic E. coli Nissle 1917, which was constructed to secrete human EGF in conjunction with the lipase ABC transporter recognition domain (LARD). Using the in vitro physically wounded monolayer model, ABC transporter-mediated EGF secretion by probiotic E. coli Nissle 1917 was demonstrated to enhance the wound-healing migration of human enterocytes. Moreover, the epithelial wound closure was dependent on EGF receptor-linked activation, which exclusively involved the subsequent signaling pathway of the mitogen-activated protein kinase kinase (MEK) extracellular-related kinases 1 and 2 (ERK1/2). In particular, the migrating frontier of the wounded edge displayed the strongest EGF receptor-linked signaling activation in the presence of the recombinant probiotic. The present study provides a basis for the clinical application of human recombinant biotherapeutics via an efficient, safe probiotic vehicle.
Microbial cultures have been used for thousands of years in food and alcoholic fermentations, and in the past century have undergone scientific scrutiny for their ability to prevent and cure a variety of diseases. This has led to the coining of the term probiotics. Today probiotics are available in a variety of food products and supplements, and have got wide applications in the control of cholestrol, cancers, allergies, etc. This article discusses the summary of research on the health benefits of probiotics and offers practical information to help health professionals and even the layman.
Although preparations incorporating prebiotics, probiotics or even both have been used for some time by individuals with irritable bowel syndrome (IBS), it is only recently that these approaches to the management of this common and challenging disorder have attracted the attention of medical scientists and clinicians. This interest is, in large part, related to the explosion in understanding of the gut microbiota in health and disease - recent data have, indeed, implicated the microbiota in IBS. While clinical scientists develop a rationale for the use probiotics and prebiotics in IBS, others have been subjecting these products to the rigors of high-quality clinical trials. Although several lines of evidence now provide a plausible basis for the use of interventions that seek to modify the microbiota in IBS, the number of appropriately powered, optimally designed clinical trials still remains small. Probiotic trials in IBS are difficult to compare because of differences in dose, strain and formulation - however, available evidence does suggest that benefits do come from the use of probiotics. In some instances, the effects are limited to some individual IBS symptoms, whereas in others, there seems to be a more global impact. Data to support the use of prebiotics are more limited at this stage. The microbiota-host interface has proven to be a fertile ground for research in IBS and offers therapeutic potential for this common disorder.
Probiotics are live microorganisms that are able to confer health benefits on the host, in most cases through their interaction with the local gastrointestinal environment. Traditionally, they have been selected for their technological parameters, without following a scientific rationale for specific applications. However, high-throughput methodologies have allowed the scientific community to establish novel probiotic markers, potentially helping to understand the probiotic effect, as well as traits related to the robustness of these microorganisms. These markers could be used for strain selection and included among the selection criteria for new probiotics. Furthermore, strategies directed at enhancing the functionality of the already available strains have also been developed.