Microorganisms said to provide health benefits when consumed
Not to be confused with
Prebiotics, food compounds that induce the growth or activity of microorganisms.
Probiotics are live
microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the
gut microbiota.[1][2] Probiotics are considered
generally safe to consume, but may cause
bacteria-
host interactions and unwanted
side effects in rare cases.[3][4][5] There is some evidence that probiotics are beneficial for some conditions, but there is little evidence for many of the health benefits claimed for them.[1]
The first discovered probiotic was a certain strain of
bacillus in Bulgarian yoghurt, called Lactobacillus bulgaricus. The discovery was made in 1905 by Bulgarian physician and microbiologist
Stamen Grigorov. The modern-day theory is generally attributed to Russian
Nobel laureateÉlie Metchnikoff, who postulated around 1907 that
yoghurt-consuming Bulgarian peasants lived longer.[6]
An October 2001 report by the
World Health Organization (WHO) defines probiotics as "live microorganisms which when administered in adequate amounts confer a health benefit on the host."[13][14] Following this definition, a
working group convened by the
Food and Agriculture Organization (FAO)/WHO in May 2002 issued the Guidelines for the Evaluation of Probiotics in Food.[15] A consensus definition of the term probiotics, based on available information and scientific evidence, was adopted after the aforementioned joint expert consultation between the
FAO of the
United Nations and the WHO. This effort was accompanied by local governmental and supra-governmental regulatory bodies' requirements to better characterize health claims substantiations.[citation needed]
That first global effort was further developed in 2010; two expert groups of academic scientists and industry representatives made recommendations for the evaluation and validation of probiotic health claims.[16][17] The same principles emerged from those two groups as were expressed in the "Guidelines" of FAO/WHO in 2002. This definition, though widely adopted, is not acceptable to the
European Food Safety Authority because it embeds a health claim that is not measurable.[7]
A group of scientific experts assembled in Canada in October 2013 to discuss the scope and appropriate use of the term "probiotic", adjusting the definition to be "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host."[18]
Lactic acid bacteria (LABs), which are food fermenting bacteria, have the ability to prevent food spoilage and can improve the nutritive value of the foods they inhabit. Acid fermentation (as well as salting), remains one of the most practical methods of preservation of fresh vegetables, cereal gruels, and milk-cereal mixtures due to its low cost and energy requirements.[20]
The manipulation of the gut microbiota is complex and may cause bacteria-host interactions.[5] Though probiotics are considered safe, some have concerns about their safety in certain cases.[5][41] Some people, such as those with
immunodeficiency,
short bowel syndrome,
central venous catheters, and
cardiac valve disease, and premature infants, may be at higher risk for adverse events.[3] In severely ill people with
inflammatory bowel disease, a risk exists for the passage of viable bacteria from the gastrointestinal tract to the internal organs (bacterial translocation) as a consequence of
bacteremia, which can cause adverse health consequences.[5] Rarely, consumption of probiotics by children with lowered immune system function or who are already critically ill may result in bacteremia or
fungemia (i.e., bacteria or fungi in the blood), which can lead to
sepsis, a potentially fatal disease.[4]
Lactobacillus species have been suggested to contribute to obesity in humans, but no evidence of this relationship has been found.[42]
Consumption
In 2015, the global retail market value for probiotics was US$41 billion, including sales of probiotic
supplements, fermented milk products, and yogurt, which alone accounted for 75% of total consumption.[43] Innovation in probiotic products in 2015 was mainly from supplements, which produced US$4 billion and was projected to grow 37% globally by 2020.[43] Consumption of yogurt products in China has increased by 20% per year since 2014.[44]
Regulation
As of 2019[update], the
European Food Safety Authority has rejected all petitions by commercial manufacturers for health claims on probiotic products in Europe due to insufficient evidence for a
cause-and-effect mechanism for benefit, thus inconclusive proof of effectiveness.[7][8][12] The
European Commission placed a ban on putting the word "probiotic" on the packaging of products because such labeling misleads consumers to believe a health benefit is provided by the product when no scientific proof exists to demonstrate that health effect.[7][45][46][47]
In the United States, the
Food and Drug Administration (FDA) and
Federal Trade Commission (FTC) have issued warning letters and imposed punishment on various manufacturers of probiotic products whose labels claim to treat a disease or condition.[10][11][48]Food product labeling requires language approved by the FDA, so probiotic manufacturers have received warning letters for making disease or treatment claims.[10][48] The FTC has taken punitive actions, including a US$21 million fine coordinated by 39 different state governments against a major probiotic manufacturer for deceptive advertising and exaggerated claims of health benefits for yogurt and probiotic dairy drink.[11]
Yogurt labeling
The
National Yogurt Association (NYA) of the United States gives a "Live & Active Cultures Seal" to refrigerated yogurt products that contain 100 million cells per gram, or frozen yogurt products that contain 10 million cells per gram at the time of manufacture.[49] In 2002, the FDA and WHO recommended that "the minimum viable numbers of each probiotic strain at the end of the shelf-life" be reported on labeling,[50] but most companies that give a number report the viable cell count at the date of manufacture, a number that could be much higher than that which exists at consumption.[51] Because of the variability in storage conditions and time before eating, exactly how many active culture cells remain at the time of consumption is difficult to determine. The survival of probiotics was strongly dependent on the storage temperature and remarkable viability loss occurred in room temperature compared to refrigerated storage.[52]
History
Probiotics have received renewed attention in the 21st century from product manufacturers, research studies, and consumers. Their history can be traced to the first use of cheese and fermented products, which were well-known to the
Greeks and
Romans who recommended their consumption.[53] The
fermentation of dairy foods represents one of the oldest techniques for
food preservation.[54]
The original modern hypothesis of the positive role played by certain bacteria was first introduced by Russian scientist and
Nobel laureateÉlie Metchnikoff, who in 1907 suggested that it would be possible to modify the
gut microbiota and to replace harmful microbes with useful microbes.[55] Metchnikoff, at that time a professor at the
Pasteur Institute in
Paris, proposed the hypothesis that the
aging process results from the activity of
putrefactive (
proteolytic) microbes producing toxic substances in the
large bowel. Proteolytic bacteria such as
clostridia, which are part of the normal gut microbiota, produce toxic substances including
phenols,
indols, and
ammonia from the
digestion of
proteins. According to
Metchnikoff, these compounds were responsible for what he called "intestinal
autointoxication", which would cause the physical changes associated with old age.[56]
At that time,
milk fermented with
lactobacillales were known to inhibit the growth of proteolytic bacteria because of the low
pH produced by the fermentation of
lactose. Metchnikoff had also observed that certain rural populations in Europe, for example in Bulgaria and the Russian steppes, who lived largely on milk fermented by lactic-acid bacteria, were exceptionally long-lived. Based on these observations, Metchnikoff proposed that consumption of fermented milk would "seed" the
intestine with harmless lactic-acid bacteria and decrease the intestinal pH, and that this would suppress the growth of proteolytic bacteria. Metchnikoff himself introduced in his diet
sour milk fermented with the bacteria he called "Bulgarian Bacillus" and believed his health benefited. Friends in Paris soon followed his example and physicians began prescribing the sour-milk diet for their patients.[57]
Bifidobacteria was first isolated from a breastfed infant by Henry Tissier, who also worked at the
Pasteur Institute. The isolated bacterium named Bacillus bifidus communis[58] was later renamed to the genus Bifidobacterium.[59] Tissier found that bifidobacteria are dominant in the gut microbiota of
breast-fed babies and he observed clinical benefits from treating infant diarrhea with bifidobacteria.
During an outbreak of
shigellosis in 1917, German professor Alfred Nissle isolated a strain of Escherichia coli from the feces of a soldier who was not affected by the disease.[60] Methods of treating infectious diseases were needed at that time when antibiotics were not yet available, and Nissle used the
E. coli Nissle 1917 strain in acute gastrointestinal infectious
salmonellosis and
shigellosis.[61]
In 1920, Rettger and Cheplin reported that Metchnikoff's "Bulgarian Bacillus", later called Lactobacillus delbrueckii subsp. bulgaricus, could not live in the human intestine.[62][non-primary source needed] They conducted experiments involving rats and humans volunteers, feeding them with Lactobacillus acidophilus. They observed the disappearance of the pathogenic protist
Balantidium coli as well as of other gas-producing bacteria.[62] Rettger further explored the possibilities of L. acidophilus, and reasoned that bacteria originating from the gut were more likely to produce the desired effect in this environment. In 1935, certain strains of L. acidophilus were found very active when implanted in the human digestive tract.[63][non-primary source needed]
Contrasting antibiotics, probiotics were defined as microbially derived factors that stimulate the growth of other microorganisms. In 1989, Roy Fuller suggested a definition of probiotics that have been widely used: "A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance."[64] Fuller's definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host.
The term "probiotic" originally referred to microorganisms that have effects on other microorganisms.[65] The concept of probiotics involved the notion that substances secreted by one microorganism stimulated the growth of another microorganism. The term was used again[66] to describe tissue extracts that stimulated microbial growth. The term probiotics was taken up by Parker,[67] who defined the concept as, "Organisms and substances that have a beneficial effect on the host animal by contributing to its intestinal microbial balance." Later, the definition was greatly improved by Fuller,[64] whose explanation was very close to the definition used today. Fuller described probiotics as a "live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance." He stressed two important claims for probiotics: the viable nature of probiotics and the capacity to help with intestinal balance.
Some literature gives the word a full Greek
etymology,[69][70] but it appears to be a composite of the Latin preposition pro, meaning 'for', and the Greek adjective βιωτικός (biōtikos), meaning 'fit for life, lively',[71] the latter deriving from the noun βίος (bios), meaning 'life'.[72] The term contrasts etymologically with the term antibiotic, although it is not a complete
antonym. The related term prebiotic comes from the Latin prae, meaning 'before', and refers to a substance that is not digested, but rather may be
fermented to promote the growth of beneficial intestinal microorganisms.[73]
Research
As food products or dietary supplements, probiotics are under preliminary research to evaluate if they provide any effect on health.[2][7][74] In all cases proposed as health claims to the
European Food Safety Authority, the scientific evidence remains insufficient to prove a cause-and-effect relationship between consumption of probiotic products and any health benefit.[7][75] There is no scientific basis for extrapolating an effect from a tested strain to an untested strain.[2][76][77] Improved health through gut flora modulation appears to be directly related to long-term dietary changes.[7][78] Claims that some lactobacilli may contribute to
weight gain in some humans[79][80] remain controversial.[81]
Acute otitis media
There is inconsistency in the results of different groups of 3488 children as reported in a Cochrane review.[82] Also, it shows no significant difference regarding the adverse effects between probiotic and the other comparators.[82]
Allergies
Only limited, low-quality evidence exists to indicate that probiotics are helpful for treating people with
milk allergy.[83] A 2015 review showed low-quality evidence that probiotics given directly to infants with
eczema, or in infants whose mothers used probiotics during the
last trimester of pregnancy and breastfeeding, had lower risk of eczema.[84]
Asthma
It is unclear whether probiotic supplementation helps with childhood
asthma, as the quality of research evidence is low.[85]
Antibiotic-associated diarrhea
Antibiotics are a common treatment for children, with 11% to 40% of antibiotic-treated children developing
diarrhea.[86]Antibiotic-associated diarrhea (AAD) results from an imbalance in the colonic microbiota caused by antibiotic therapy.[86] These microbial community alterations result in changes in
carbohydrate metabolism, with decreased
short-chain fatty acid absorption and osmotic diarrhea as a result. A 2015
Cochrane review concluded that a protective effect of some probiotics existed for AAD in children.[86] The known risks of using probiotics for treating Clostridium difficile outweighs the uncertain benefits.[87]
Probiotic treatment might reduce the incidence and severity of AAD as indicated in several
meta-analyses.[88][89][90] For example, treatment with probiotic formulations including L. rhamnosus may reduce the risk of AAD, improve stool consistency during antibiotic therapy, and enhance the immune response after vaccination.[91]
The potential efficacy of probiotics to treat AAD depends on the probiotic strains and dosage.[92][93] One review recommended for children L. rhamnosus or Saccharomyces boulardii at 5 to 40 billion colony-forming units/day, given the modest number needed to treat and the likelihood that adverse events are very rare.[86] The same review stated that probiotic use should be avoided in pediatric populations at risk for
adverse events, such as severely debilitated or
immune-compromised children.[citation needed]
Bacterial vaginosis
Probiotic treatment of bacterial vaginosis is the application or ingestion of
bacterial species found in the healthy vagina to cure the infection of bacteria causing
bacterial vaginosis. This treatment is based on the observation that 70% of healthy females have a group of bacteria in the genus Lactobacillus that dominate the population of organisms in the vagina. Specific strains of lactobacilli inhibit the growth of bacteria causing BV by producing H2O2, lactic acid, and/or bacteriocins, and/or inhibit the adherence of Gardnerella vaginalis to the vaginal epithelium, which prevents the infection from occurring in the vagina.[94] Currently, the success of probiotic treatment has been mixed, since the use of probiotics to restore healthy populations of Lactobacillus has not been standardized. Often, standard antibiotic treatment is used at the same time that probiotics are being tested. In addition, some groups of women respond to treatment based upon ethnicity, age, number of sexual partners, pregnancy, and the pathogens causing bacterial vaginosis.[95] In 2013, researchers found that administration of
hydrogen peroxide-producing strains, such as L. acidophilus and L. rhamnosus, were able to normalize vaginal pH and rebalance the
vaginal microbiota, preventing and alleviating bacterial vaginosis.[96]
A 2002 meta-analysis that included five double-blind trials examining the short-term (2–8 weeks) effects of a yogurt with probiotic strains on serum cholesterol levels found little effect of 8.5 mg/dL (0.22 mmol/L) (4% decrease) in
total cholesterol concentration, and a decrease of 7.7 mg/dL (0.2 mmol/L) (5% decrease) in serum
LDL concentration.[98]
Depression and anxiety
A 2019 meta-analysis found low-quality evidence for probiotics having a small improvement in
depression and
anxiety.[99] A 2020 review found probiotics might improve depression, but more studies are needed.[100]
Diarrhea
Some probiotics are suggested as a possible treatment for various forms of
gastroenteritis.[101] As a treatment for infectious diarrhea, probiotics are of no benefit to people who have the condition for more than two days, and there is no evidence they lessen the duration of diarrhea overall.[102]
Dermatitis
Probiotics are commonly given to breastfeeding mothers and their young children to prevent eczema (
dermatitis), but no good evidence shows efficacy for this purpose.[103] There is little evidence to support the use of probiotics to treat
atopic dermatitis, and some risk of
adverse effects.[104] The
American Academy of Dermatology stated: "The use of probiotics/prebiotics for the treatment of patients with established atopic dermatitis is not recommended due to inconsistent evidence".[105]
Glycemic control
According to an umbrella review of meta-analyses of randomized controlled trials, probiotics supplementation reduces glucose homeostasis. This can be an effective therapy for lowering high blood sugar levels unless the body becomes
hypoglycemic; caution and glucose monitoring are necessary to avoid this. [106]
Helicobacter pylori
Some strains of lactic acid bacteria (LAB) may affect Helicobacter pylori infections (which may cause
peptic ulcers) in adults when used in combination with standard medical treatments, but no standard in medical practice or regulatory approval exists for such treatment.[107] The only peer-reviewed treatments for H. pylori to date all include various Antibiotic Regimens.[108]
Immune function and infections
Some strains of LAB may affect
pathogens by means of
competitive inhibition (i.e., by competing for growth) and some evidence suggests they may improve immune function by increasing the number of
IgA-producing plasma cells and increasing or improving
phagocytosis, as well as increasing the proportion of
T lymphocytes and natural killer cells.[109][110] LAB products might aid in the treatment of acute diarrhea and possibly affect
rotavirus infections in children and travelers' diarrhea in adults,[109][110] but no products are approved for such indications. There are weak evidence probiotics might lower the incidence of acute upper respiratory tract infections in adults, they were better than placebo or no treatment.[111]
Probiotics do not appear to change the risk of infection in older people.[112]
Inflammatory bowel disease
The use of oral probiotic supplements to modify the composition and behaviour of the microbiome has been considered as a possible therapy for both induction and maintenance of remission in people with Crohn's disease and ulcerative colitis. A Cochrane review in 2020 did not find clear evidence of improved remission likelihood, nor lower adverse events, in people with Crohn's disease, following probiotic treatment. [113]
For ulcerative colitis, there is low-certainty evidence that probiotic supplements may increase the probability of clinical remission. [114] People receiving probiotics were 73% more likely to experience disease remission and over 2x as likely to report improvement in symptoms compared to those receiving a placebo, with no clear difference in minor or serious adverse effects. [114]Although there was no clear evidence of greater remission when probiotic supplements were compared with
5‐aminosalicylic acid treatment as a
monotherapy, the likelihood of remission was 22% higher if probiotics were used in combination with 5-aminosalicylic acid therapy. [114] Whereas in people who are already in remission, it is unclear whether probiotics help to prevent future relapse, either as a monotherapy or
combination therapy. [115]
Irritable bowel syndrome
Probiotics are under study for their potential to affect
irritable bowel syndrome, although uncertainty remains around which type of probiotic works best, and around the size of possible effect.[116][117]
Necrotizing enterocolitis
Several clinical studies provide evidence for the potential of probiotics to lower the risk of
necrotizing enterocolitis and mortality in premature infants. One meta-analysis indicated that probiotics reduce these risks by more than 50% compared with controls but that further, large, high-quality trials were needed to inform policy and practice.[118]
Pregnancy
A Cochrane systematic review found no good evidence that probiotics were of benefit in reducing the risk of
gestational diabetes, but good evidence that they increased the risk of
pre-eclampsia. For this reason, the use of probiotics in pregnancy was advised against.[119]
Recurrent abdominal pain
A 2017 review based on moderate to low-quality evidence suggests that probiotics may be helpful in relieving pain in the short term in children with recurrent abdominal pain, but the proper strain and dosage are not known.[120]
Dry eye
A clinical study investigating the impact of probiotics in relieving the signs and symptoms of
dry eye revealed promising results for the ophthalmic formulation of
Latilactobacillus sakei, while the oral probiotic demonstrated no discernible benefits.[121]
Urinary tract
There is limited evidence indicating probiotics are of benefit in the management of infection or inflammation of the
urinary tract.[122] One literature review found Lactobacillus probiotic supplements appeared to increase vaginal lactobacilli levels, thus reducing the incidence of vaginal infections in otherwise healthy adult women.[123]
General research
Formulations
Supplements such as tablets, capsules, powders, and sachets containing bacteria have been studied. However, probiotics taken orally can be destroyed by the acidic conditions of the stomach. As of 2010, a number of
microencapsulation techniques were being developed to address this problem.[124]
Multiple probiotics
Preliminary research is evaluating the potential
physiological effects of multiple probiotic strains, as opposed to a single strain.[125][126] As the human gut may contain tens of thousands of microbial species, one theory indicates that this diverse environment may benefit from consuming multiple probiotic strains, an effect that remains scientifically unconfirmed.[citation needed]
Strains
Only preliminary evidence exists for most probiotic health claims. Even for the most studied probiotic
strains, few have been sufficiently developed in basic and clinical research to warrant approval for
health claim status by a regulatory agency such as the FDA or EFSA, and as of 2010[update], no claims had been approved by those two agencies.[7] Some experts are skeptical about the efficacy of different probiotic strains and believe that not all subjects benefit from probiotics.[7][127]
Scientific guidelines for testing
First, probiotics must be alive when administered.[64][128][129] One of the concerns throughout the
scientific literature resides in the viability and reproducibility on a large scale of observed results for specific studies, as well as the viability and stability during use and storage, and finally the ability to survive in stomach acids and then in the intestinal ecosystem.[7][failed verification]
Second, probiotics must have undergone controlled evaluation to document health benefits in the target host. Only products that contain live organisms shown in reproducible human studies to confer a health benefit may claim to be probiotic.[7][130][131] The correct definition of health benefit, backed with solid scientific evidence, is a strong element for the proper identification and assessment of the effect of a probiotic. This aspect is a challenge for scientific and industrial investigations because several difficulties arise, such as variability in the site for probiotic use (oral, vaginal, intestinal) and mode of application.[64]
Third, the probiotic candidate must be a taxonomically defined microbe or combination of microbes (
genus,
species, and strain level). It is commonly admitted that most effects of probiotics are strain-specific and cannot be extended to other probiotics of the same genus or species.[128] This calls for precise identification of the strain, i.e.
genotypic and
phenotypic characterization of the tested microorganism.[16]
Fourth, probiotics must be safe for their intended use. The 2002 FAO/WHO guidelines recommend that, though bacteria may be generally recognized as safe (GRAS), the safety of the potential probiotic be assessed by the minimum required tests: [132]
Assessment of certain metabolic activities (e.g. D-lactate production, bile salt deconjugation)
Assessment of side effects in human studies
Determination of antibiotic resistance patterns
Epidemiological surveillance of adverse incidents in consumers (aftermarket)
If the strain under evaluation belongs to a species known to produce toxins in mammals, it must be tested for toxin production. One possible scheme for testing toxin production has been recommended by the EU Scientific Committee on Animal Nutrition.[133]
If the strain under evaluation belongs to a species with known
hemolytic potential, determination of hemolytic activity is required.
In Europe, EFSA adopted a premarket system for the safety assessment of microbial species used in food and feed productions to set priorities for the need for risk assessment. The assessment is made for certain microorganisms; if the result is favorable, it leads to "Qualified Presumption of Safety" status.[134]
^
ab"Probiotics". National Health Service. 27 November 2018.
Archived from the original on 20 April 2021. Retrieved 2 November 2019.
^
abc"Probiotics: What You Need To Know". National Center for Complementary and Integrative Health, US National Institutes of Health. 1 August 2019.
Archived from the original on 17 September 2018. Retrieved 10 November 2019.
^
abcEngle MK, Roosevelt MW, Waltrip EA (22 November 2011).
"Warning letter to CocoKefir LLC". Compliance Branch, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration and Federal Trade Commission. Archived from the original on 23 October 2016. Retrieved 4 June 2016.{{
cite web}}: CS1 maint: bot: original URL status unknown (
link)
^
abBreidt F, McFeeters RF, Perez-Diaz I, Lee CH (2013).
"Fermented Vegetables"(PDF). Fermented Vegetables; In: Food Microbiology: Fundamentals and Frontiers, 4th Ed. Washington, DC: ASM Press. pp. 841–855.
doi:
10.1128/9781555818463.ch33.
ISBN978-1-55581-626-1.
Archived(PDF) from the original on 28 May 2015. Retrieved 19 May 2016.
^Oh CK, Oh MC, Kim SH (2004). "The Depletion of Sodium Nitrite by Lactic Acid Bacteria Isolated from Kimchi". Journal of Medicinal Food. 7 (1): 38–44.
doi:
10.1089/109662004322984680.
PMID15117551.
^Ehrlich SD (2011-05-24).
"Lactobacillus acidophilus". University of Maryland Medical Center (UMMC).
Archived from the original on 2015-09-11. Retrieved 2015-09-17.
^Plessas S, Alexopoulos A, Voidarou C, Stavropoulou E, Bezirtzoglou E (2011). "Microbial ecology and quality assurance in food fermentation systems. The case of kefir grains application". Anaerobe. 17 (6): 483–485.
doi:
10.1016/j.anaerobe.2011.03.014.
PMID21497663.
^Shiby VK, Mishra HN (2013). "Fermented milks and milk products as functional foods – a review". Critical Reviews in Food Science and Nutrition. 53 (5): 482–496.
doi:
10.1080/10408398.2010.547398.
PMID23391015.
S2CID3059150.
^Jarrell J, Cal T, Bennett JW (2000). "The Kombucha Consortia of yeasts and bacteria". Mycologist. 14 (4): 166–170.
doi:
10.1016/S0269-915X(00)80034-8.
^Jonas R, Farah LF (1998). "Production and application of microbial cellulose". Polymer Degradation and Stability. 59 (1–3): 101–106.
doi:
10.1016/s0141-3910(97)00197-3.
^'Probiotic' As A General Descriptor(PDF) (Report). Yogurt & Live Fermented Milks Association (YLFA).
Archived(PDF) from the original on 13 December 2014. Retrieved 12 December 2014.
^"Probiotic health claims". Food Safety Authority of Ireland, Dublin. 2014.
Archived from the original on 10 July 2017. Retrieved 13 December 2014.
^
abSchmidt N (30 July 2014).
"Warning letter to Plexus Worldwide Inc". Compliance Branch, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration.
Archived from the original on 8 May 2017. Retrieved 9 May 2017.
^Gismondo MR, Drago L, Lombardi A (1999). "Review of probiotics available to modify gastrointestinal flora". Int. J. Antimicrob. Agents. 12 (4): 287–292.
doi:
10.1016/s0924-8579(99)00050-3.
PMID10493604.
^Liddell HG, Scott R (eds.).
"βιωτικός". A Greek-English Lexicon.
Archived from the original on 2023-04-25. Retrieved 2021-02-21 – via
Perseus Project.
^Million M, Raoult D (February 2013). "Species and strain specificity of Lactobacillus probiotics effect on weight regulation". Microbial Pathogenesis. 55: 52–54.
doi:
10.1016/j.micpath.2012.09.013.
PMID23332210.
^Qamer S, Deshmukh M, Patole S (August 2019). "Probiotics for cow's milk protein allergy: a systematic review of randomized controlled trials". Eur. J. Pediatr. (Review). 178 (8): 1139–1149.
doi:
10.1007/s00431-019-03397-6.
PMID31230196.
S2CID195259677.
^Lin J, Zhang Y, He C, Dai J (September 2018). "Probiotics supplementation in children with asthma: A systematic review and meta-analysis". J Paediatr Child Health (Systematic review). 54 (9): 953–961.
doi:
10.1111/jpc.14126.
PMID30051941.
S2CID51723667.
^Szajewska H, Ruszczyński M, Radzikowski A (September 2006). "Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials". J Pediatr. 149 (3): 367–372.
doi:
10.1016/j.jpeds.2006.04.053.
PMID16939749.
S2CID28439228.
^Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE (June 2006). "Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials". Lancet Infect Dis. 6 (6): 374–382.
doi:
10.1016/S1473-3099(06)70495-9.
PMID16728323.
^Borges S, Silva J, Teixeira P (March 2014). "The role of lactobacilli and probiotics in maintaining vaginal health". Arch. Gynecol. Obstet. (Review). 289 (3): 479–489.
doi:
10.1007/s00404-013-3064-9.
PMID24170161.
S2CID23954527.
^Robles-Vera I, Toral M, Romero M, Jiménez R, Sánchez M, Pérez-Vizcaíno F, Duarte J (April 2017). "Antihypertensive Effects of Probiotics". Curr. Hypertens. Rep. (Review). 19 (4): 26.
doi:
10.1007/s11906-017-0723-4.
PMID28315049.
S2CID3834130.
^Ansari F, Pourjafar H, Tabrizi A, Homayouni A (2020). "The effects of probiotics and prebiotics on mental disorders: A review on depression, anxiety, Alzheimer, and autism spectrum disorders". Current Pharmaceutical Biotechnology. 21 (7): 555–565.
doi:
10.2174/1389201021666200107113812.
ISSN1873-4316.
PMID31914909.
S2CID210121155.
^Cuello-Garcia CA, Brożek JL, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Terracciano L, Gandhi S, Agarwal A, Zhang Y, Schünemann HJ (2015). "Probiotics for the prevention of allergy: A systematic review and meta-analysis of randomized controlled trials". J. Allergy Clin. Immunol. (Systematic review & meta-analysis). 136 (4): 952–961.
doi:
10.1016/j.jaci.2015.04.031.
PMID26044853.
^Xu D, Fu L, Pan D, Chu Y, Feng M, Lu Y, Yang C, Wang Y, Xia J, Sun G (2022). "Role of probiotics/synbiotic supplementation in glycemic control: A critical umbrella review of meta-analyses of randomized controlled trials". Critical Reviews in Food Science and Nutrition. 64 (6): 1–19.
doi:
10.1080/10408398.2022.2117783.
PMID36052685.
S2CID252009294.
^Hamilton-Miller JM (October 2003). "The role of probiotics in the treatment and prevention of Helicobacter pylori infection". International Journal of Antimicrobial Agents. 22 (4): 360–366.
doi:
10.1016/S0924-8579(03)00153-5.
PMID14522098.
^Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EM (March 2010). "The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review". Gut (Systematic review). 59 (3): 3253–3232.
doi:
10.1136/gut.2008.167270.
PMID19091823.
S2CID18281136.
^Newlove-Delgado TV, Martin AE, Abbott RA, Bethel A, Thompson-Coon J, Whear R, et al. (2017).
"Dietary interventions for recurrent abdominal pain in childhood". Cochrane Database Syst Rev. 2017 (3): CD010972.
doi:
10.1002/14651858.CD010972.pub2.
PMC6464236.
PMID28334433. Overall, there is some evidence to suggest that probiotics may be effective in the treatment of RAP, in terms of improving pain in the shorter term. Clinicians may therefore consider probiotic interventions as part of the management strategy for children with RAP (Recurrent Abdominal Pain). However, we were unable to recommend the optimum strain and dosage of probiotics based on this review. The evidence for the effectiveness of probiotics was based largely on shorter-term outcomes. Further trials are required to assess whether improvements in pain are maintained over the longer term; these trials should also consider the importance of using validated and consistent scales to measure pain and other outcomes.
^Shortliffe L (2011). "Chapter 116: Infection and Inflammation of the Pediatric Genitourinary Tract". In Wein AJ (ed.). Campbell-Walsh Urology. Vol. 4 (10th ed.). Saunders Elsevier. p. 3121.
ISBN978-1-4160-6911-9.
^Timmerman HM, Koning CJ, Mulder L, Rombouts FM, Beynen AC (November 2004). "Monostrain, multistrain and multispecies probiotics – A comparison of functionality and efficacy". Int. J. Food Microbiol. 96 (3): 219–233.
doi:
10.1016/j.ijfoodmicro.2004.05.012.
PMID15454313.