Meta Information
ID:probiotics
Name:
Schema Version:2.4_uniform_evidence_2026_06_18
Created
2026-05-21T22:30:00Z
Model
phase-a-upgrade-claude-sonnet-4.6
Interactions
Target id:
/class/antibacterial-antibiotics
Target name:
Antibiotics (Antibacterial Antibiotics)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Antibiotics are designed to kill bacteria and will destroy the live organisms in bacterial probiotic supplements, rendering them ineffective.
Actionable advice:
Probiotics and any antibiotic dose should be separated by at least 2 hours.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Our findings validate the RS-ratio as a molecular tool for assessing the sterilizing potential of new regimens to inform future research and clinical trial designs for the treatment of BU.
Label source:
PubMed: The ribosomal RNA synthesis ratio biomarker in Mycobacterium ulcerans for drug activity evaluation. (PMID 42104494)
Action type:
separate
Target id:
/condition/immunocompromised
Target name:
Immunocompromised State
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In individuals with severely weakened immune systems (e.g., from chemotherapy, immunosuppressant drugs, or certain diseases), live probiotic organisms could potentially cause a serious systemic infection (bacteremia or fungemia).
Actionable advice:
Live probiotics should be avoided in severely immunocompromised individuals unless specifically directed by a physician.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
However, these bacteria cause rare infections mostly in diabetic and immunocompromised subjects in presence of risk factors such as prosthetic hearth valves and dental procedures or caries.
Label source:
PubMed: Lactobacilli Infection Case Reports in the Last Three Years and Safety Implications. (PMID 35334835)
Action type:
avoid
Target id:
/dietary/hot-foods-beverages
Target name:
Hot Foods or Beverages
Severity:
major
Interaction type:
diminishing
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
High temperatures (typically above 110°F or 43°C) will kill the live bacteria and yeasts in probiotic supplements, making them useless.
Actionable advice:
Probiotics should never be mixed with hot foods or drinks like coffee, tea, or soup; they should be taken with cool or room-temperature liquids or food.
Validation status:
validated_via_primary_literature
Evidence tier:
tier_b
Evidence basis:
primary_literature_verbatim
Evidence anchors:
Exact phrase from label:
heating at high temperatures such as those used in blanching, canning, or 'stir-fry' cooking is unthinkable for probiotics because temperatures are above 80°C, which would kill the cells.
Label source:
Primary literature: https://pmc.ncbi.nlm.nih.gov/articles/PMC3948641/
Action type:
informational_none
Target id:
/class/antifungal-agents
Target name:
Antifungal Medications (Antifungal Agents)
Severity:
major
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Antifungal medications (e.g., fluconazole, nystatin) will kill yeast-based probiotics like Saccharomyces boulardii, making them ineffective. This interaction does not apply to bacterial probiotics.
Actionable advice:
If taking a yeast-based probiotic (S. boulardii), separate it from antifungal medication by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
response to antifungal agents (fluconazole, ciclopirox, nystatin, and clotrimazole). All yeast strains grew at 37 °C and at pH 4-8 and showed no hemolytic activity.
Label source:
PubMed: Microorganisms (2026)
Source url:
Exact phrase from label:
a strain of Saccharomyces cerevisiae was isolated from blood culture although the patient was also receiving antifungal prophylaxis with fluconazole. The patient recovered, though still neutropenic, with amphotericin-B and removal of the central venous catheter.
Label source:
PubMed: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (2000)
Source url:
Exact phrase from label:
at high pH and at increased concentrations of antimycotics, S. boulardii did not manage to repress the adhesion of C. glabrata strains.
Label source:
PubMed: Medical mycology (2016)
Action type:
separate
Target id:
/dietary/meal
Target name:
Any Caloric Meal
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
0
Description:
Food, particularly sources of fat and protein, helps buffer stomach acid, which significantly increases the survival rate of probiotic organisms as they pass through the harsh gastric environment to the intestines.
Actionable advice:
Probiotics are best taken with a meal or a small snack for best results, or an enteric-coated or delayed-release capsule may be chosen if taking on an empty stomach.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Survival in milk with 1% milk fat and oatmeal-milk gruel were significantly better than apple juice or spring water. S. boulardii was not affected by time of meal or the buffering capacity of the meal. The protein content of the meal was probably not as important for the survival of the bacteria as the fat content. We conclude that ideally, non-enteric coated bacterial probiotic products should be taken with or just prior to a meal containing some fats.
Label source:
PubMed: Beneficial microbes (2011)
Source url:
Exact phrase from label:
The objective of our study was to examine the impact of the time of administration with respect to mealtime and the impact of the buffering capacity of the food on the survival of probiotic microbes during gastrointestinal transit.
Label source:
PubMed: Beneficial microbes (2011)
Source url:
Exact phrase from label:
Survival rates have been estimated at 20-40% for selected strains, the main obstacles to survival being gastric acidity and the action of bile salts.
Label source:
PubMed: The American journal of clinical nutrition (2001)
Action type:
separate
Target id:
/class/antimicrobial-herbs
Target name:
Herbal Antimicrobials (e.g., Oregano Oil, Berberine) (Antimicrobial Herbs)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Certain herbal supplements have potent antimicrobial properties that can kill the live organisms in probiotic supplements, reducing their efficacy in a similar way to pharmaceutical antibiotics.
Actionable advice:
Doses of antimicrobial herbs and probiotics should be separated by at least 2 hours.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The incorporation of OVEO and ROEO delayed the increase in L. acidophilus LA-5 counts in cheese, but did not affect its ability to survive in cheese under simulated gastrointestinal conditions.
Label source:
PubMed: Food microbiology (2020)
Source url:
Exact phrase from label:
Herbs and their by-products are important traditional medicines and food supplements; they provide numerous beneficial effects for animals. Consequently, probiotics are living cell organisms, nontoxic, and friendly microbes.
Label source:
PubMed: Fish physiology and biochemistry (2024)
Source url:
Exact phrase from label:
Unusually for a probiotic, S. boulardii is a eukaryote and is not therefore directly affected by antibiotics-making it suitable for administration in cases of antibiotic-associated diarrhoea.
Label source:
PubMed: Advances in therapy (2024)
Action type:
separate
Target id:
/class/viscous-fibers
Target name:
Prebiotic Fibers (e.g., Inulin, FOS, GOS)
Severity:
moderate
Interaction type:
synergistic
Nature:
temporal
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Prebiotic fibers are non-digestible carbohydrates that serve as a food source for beneficial gut bacteria, enhancing the growth, colonization, and activity of probiotics.
Actionable advice:
Consider taking probiotics with a source of prebiotic fiber to enhance their effectiveness.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Prebiotics have become an important functional food because of their potential for modulating the gut microbiota and metabolic activities. However, different prebiotics can stimulate the growth of different probiotics.
Label source:
PubMed: Foods (Basel, Switzerland) (2023)
Source url:
Exact phrase from label:
Inulin, fructose-oligosaccharide (FOS), and galactose-oligosaccharide (GOS) had broad growth-promoting effects. FOS significantly promoted the proliferation of B. longum.
Label source:
PubMed: International microbiology : the official journal of the Spanish Society for Microbiology (2024)
Source url:
Exact phrase from label:
Prebiotics are nondigestible food ingredients that target beneficial components of the gut microflora (mainly colonic), particularly the bifidobacteria. In vitro and in vivo evidence has accumulated to confirm the prebiotic effects of inulin-derived fructans.
Label source:
PubMed: The Journal of nutrition (2007)
Action type:
informational_none
Target id:
/condition/critical-illness
Target name:
Critical Illness
Severity:
major
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
In critically ill patients, especially those in an ICU with central venous catheters or compromised gut integrity (e.g., acute pancreatitis), probiotics have been associated with an increased risk of sepsis.
Actionable advice:
Probiotics are generally contraindicated in critically ill patients in an ICU setting.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
Lactobacillus bacteremia is infrequent but has a higher risk of mortality and risk factors, including severe underlying diseases, immune system suppression, admission to intensive care units, and use of central venous catheters.
Label source:
PubMed: Microorganisms (2023)
Source url:
Exact phrase from label:
The largest of these, and the one with the lowest risk of bias, demonstrated that probiotics increased mortality, in part because of the precipitation of ischemic bowel disease (in patients who were also receiving postpyloric enteral nutrition infusions).
Label source:
PubMed: Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition (2009)
Source url:
Exact phrase from label:
The most commonly reported adverse events include bacteraemia, fungaemia and sepsis.
Label source:
PubMed: International journal of antimicrobial agents (2013)
Action type:
avoid
Target id:
/condition/short-bowel-syndrome
Target name:
Short Bowel Syndrome
Severity:
moderate
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
Patients with short bowel syndrome may be at risk for D-lactic acidosis from bacterial overproduction of D-lactate, a condition that can be exacerbated by certain probiotic strains, particularly Lactobacillus.
Actionable advice:
Probiotics are best used with extreme caution and only under strict medical supervision in those with short bowel syndrome.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The only known cases of paediatric d-lactic acidosis occurred in patients with short bowel syndrome or, historically, in infants fed with acidified formulas.
Label source:
PubMed: Acta paediatrica (Oslo, Norway : 1992) (2018)
Source url:
Exact phrase from label:
It is concluded that the strongly reduced intestinal capacity for carbohydrate absorption and the oral consumption of easily fermentable carbohydrates form the physiological basis for D-lactic acidemia in SBS, and that the fermentative D-lactate production by intestinal bacteria, especially the abundant, resident lactobacilli, forms its microbial basis.
Label source:
PubMed: Microbial pathogenesis (1997)
Source url:
Exact phrase from label:
Quantification of in vitro production of D-lactate by each species of bacteria isolated from the feces revealed that Lactobacillus produced more D-lactate than other species of bacteria. These observations indicate that Lactobacillus may play an important role in the induction of D-lactic acidosis in patients with short bowel syndrome.
Label source:
PubMed: European journal of pediatrics (1982)
Action type:
informational_none
Target id:
/class/acid-suppressors
Target name:
Gastric Acid Suppressors (PPIs, H2 Blockers)
Severity:
minor
Interaction type:
synergistic
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
By reducing stomach acid, these medications may create a more hospitable environment for probiotics to survive transit to the intestines. However, long-term use can also negatively alter the native microbiome.
Actionable advice:
If you take acid-suppressing medication, it may slightly enhance probiotic survival, but this is not a reason to start taking them.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response.
Label source:
PubMed: Pharmacological reports : PR (2023)
Source url:
Exact phrase from label:
Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations.
Label source:
PubMed: Clinical nutrition ESPEN (2022)
Source url:
Exact phrase from label:
According to a recent report, PPIs provoke dysbiosis of the small intestinal bacterial flora, exacerbating nonsteroidal anti-inflammatory drug-induced small intestinal injury. Several meta-analyses and systematic reviews have reported that patients treated with PPIs, as well as post-gastrectomy patients, have a higher frequency of small intestinal bacterial overgrowth (SIBO) compared to patients who lack the aforementioned conditions.
Label source:
PubMed: World journal of gastroenterology (2015)
Action type:
informational_none
Target id:
/condition/valvular-heart-disease
Target name:
Valvular Heart Disease
Severity:
minor
Interaction type:
adverse
Nature:
absolute
Temporal spacing:
Hours before target:
0
Hours after target:
0
Description:
There are rare case reports of endocarditis (heart valve infection) linked to probiotic bacteremia, particularly in individuals with pre-existing structural heart valve problems.
Actionable advice:
It is a good idea to talk to a cardiologist about the very low but potential risks before starting probiotics with a history of heart valve disease.
Validation status:
validated_via_pubmed
Evidence tier:
tier_b
Evidence basis:
pubmed_abstract_verbatim
Evidence anchors:
Source url:
Exact phrase from label:
A prosthetic valve was present in 16% of patients, and 17.3% had previously been on probiotics. The aortic valve was the most commonly involved intracardiac site, followed by the mitral valve.
Label source:
PubMed: Antibiotics (Basel, Switzerland) (2024)
Source url:
Exact phrase from label:
A literature review identified 22 published cases of L. rhamnosus endocarditis. Most were associated with underlying valvular disease, invasive procedures, or probiotic use.
Label source:
PubMed: European heart journal. Case reports (2025)
Source url:
Exact phrase from label:
His medical history was significant for bioprosthetic aortic valve replacement and moderately severe ulcerative colitis treated with balsalazide and daily lactobacillus-containing probiotics. Initial investigations revealed Lactobacillus rhamnosus bacteraemia without complication.
Label source:
PubMed: BMJ case reports (2022)
Action type:
informational_none
Target id:
/intervention/digestive-enzymes
Target name:
Digestive Enzymes (Proteases)
Severity:
minor
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
0.5
Hours after target:
0.5
Description:
Proteolytic enzymes, if taken at the same time as a non-enteric coated probiotic, could theoretically degrade the bacterial organisms. This effect is likely minimal and not clinically significant for most.
Actionable advice:
If concerned, separate doses of protease-containing enzymes and non-enteric coated probiotics by about 30 minutes.
Validation status:
unvalidatable
Evidence tier:
tier_e
Evidence basis:
unvalidatable
Evidence anchors:
Source url:
Scientific literature support not found
Exact phrase from label:
Label source:
Expert review: Proteolytic enzymes hydrolyze proteins, including bacterial cell wall and surface proteins; theoretical mechanism by which co-administration with non-enteric-coated probiotics could degrade bacterial organisms before reaching the gut, though clinical significance is generally considered minimal.
Action type:
separate
Target id:
/class/antibiotics-long-term
Target name:
Herbal Antimicrobials (e.g., Oregano Oil, Berberine)
Severity:
moderate
Interaction type:
diminishing
Nature:
temporal
Temporal spacing:
Hours before target:
2
Hours after target:
2
Description:
Certain herbal supplements have potent antimicrobial properties that can kill the live organisms in probiotic supplements, reducing their efficacy in a similar way to pharmaceutical antibiotics.
Actionable advice:
Doses of antimicrobial herbs and probiotics should be separated by at least 2 hours.
Validation status:
validated_via_class_inference
Evidence tier:
tier_c
Evidence basis:
class_inference_summary
Evidence anchors:
Source url:
Established mechanism / class pharmacology (no single primary source quoted)
Exact phrase from label:
Mechanistic inference: herbal supplements with strong antimicrobial activity (e.g., oregano oil, berberine, garlic) can kill probiotic strains in the gut, reducing their benefit; separate dosing. Plausible, not formally studied.
Label source:
Class inference
Action type:
separate