What’s in the web for family physicians – probiotics

Wilbert WB Wong 王維斌，Alfred KY Tang 鄧權恩

HK Pract 2022;44:29-32

Probiotics are live microorganisms similar to the beneficial bacteria that occur naturally in the human gut. They are available over-the-counter in different forms such as capsules, packets, or food supplements. Probiotics have been used to treat multiple medical conditions especially gastrointestinal problems. However, evidences supporting their use have often been conflicting. A good understanding on this topic can provide more updated information to our patients.

According to the International Scientific Association for Probiotics and Prebiotics, “probiotics” is defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host”. These microorganisms, which consist mainly of bacteria but also include yeasts, are naturally present in fermented foods, may be added to other food products, and are available as dietary supplements.

Probiotics should not be confused with prebiotics, which are typically complex carbohydrates (such as inulin and other fructo-oligosaccharides) that microorganisms in the gastrointestinal tract use as metabolic fuel. Commercial products containing both prebiotic sugars and probiotic organisms are often called “synbiotics.” In addition, products containing dead microorganisms and those made by microorganisms (such as proteins, polysaccharides, nucleotides, and peptides) are, by definition, not probiotics.

Probiotics are identified by their specific strain, which includes the genus, the species, the subspecies (if applicable), and an alphanumeric strain designation. The seven core genera of microbial organisms most often used in probiotic products are Lactobacillus, Bifidobacterium, Saccharomyces, Streptococcus, Enterococcus, Escherichia, and Bacillus.

Probiotics are measured in colony forming units (CFU), which indicate the number of viable cells. Amounts may be written on product labels as, for example, 1 x 109 for 1 billion CFU or 1 x 1010 for 10 billion CFU. Many probiotic supplements contain 1 to 10 billion CFU per dose, but some products contain up to 50 billion CFU or more. However, higher CFU counts do not necessarily improve the product’s health effects.

Probiotics : What you need to know?

This website supported by the National Center for Complementary and Integrative Health (NCCIH) provides a comprehensive introduction to the nature and use of probiotics. NCCIH is the US Federal Government’s leading agency for scientific research on complementary and integrative health approaches, which operates under the National Institutes of Health (NIH) within the U.S. Department of Health and Human Services.

A great deal of research has been done on probiotics, but much remains to be studied on whether they are helpful and safe for various health conditions. Probiotics have shown promising for a variety of health purposes, including prevention of antibiotic-associated diarrhea (including diarrhea caused by Clostridium difficile), prevention of necrotising enterocolitis and sepsis in premature infants, treatment of infant colic, treatment of periodontal disease, and induction or maintenance of remission in ulcerative colitis.

Using probiotics in clinical practice: Where are we now? A review of existing meta- analyses

This scientific literature demonstrated that probiotics have a broad spectrum of activities, although the results may be contradictory. This study published in 2017 provides a critical overview of the current meta-analyses that have evaluated the efficacy of probiotics in physiologic and pathological conditions, such as metabolic disease, antibiotic-associated and Clostridium difficile-associated diarrhea, Irritable bowel syndrome, constipation, Inflammatory bowel disease, chemotherapy-associated diarrhea, respiratory tract infection, ventilator-associated pneumonia, liver encephalopathy, periodontitis, depression, vaginosis, urinary tract infections, pancreatitis, incidence of ventilator-associated pneumonia, hospital infection and stay in Intensive Care Unit, mortality of post-trauma patients, necrotising enterocolitis in premature infants.

The effects of probiotics are considered “evidencebased” only for antibiotic- and Clostridium difficileassociated diarrhea. For other diagnoses, meta-analyses are still lacking to confirm the type and biologic effect of probiotic strains, as well as the outcome of the disease condition. Hopefully, the results presented would be a stimulus for further studies which will provide clinical recommendations.

Probiotics for treating eczema

Eczema is a common skin condition of long duration. Probiotics have been proposed as an effective treatment for eczema; their use is increasing, as numerous clinical trials are under way. This study, published in 2018, was an update of a Cochrane Review first published in 2008. It suggested that probiotics may not be an effective treatment for eczema but had identified areas in which evidence was lacking.

The probiotics used were bacteria of the Lactobacillus and Bifidobacteria species, which were taken alone or combined with other probiotics, and were given with or without prebiotics. Comparators were no treatment, placebo, and other treatments with no probiotics. Data suggested that probiotics currently in use probably make little or no difference in patientrated eczema symptoms (moderate-quality evidence) and may make no difference in quality of life for people with eczema (low-quality evidence). Current use of probiotics for treatment of eczema is not evidence-based.

The authors found no evidence to suggest that probiotic treatment is unsafe; however, reports from non-randomised controlled trials indicate that it can lead to adverse events including sepsis and bowel ischaemia.

Probitoics for the prevention of paediatric antibiotics diarrhea

Antibiotics make changes in the microbial balance and may result in antibiotic-associated diarrhea (AAD). Probiotics may prevent AAD via providing gut barrier, restoration of the gut microflora, and other potential mechanisms of action.

The primary objectives of the study were to assess the efficacy and safety of probiotics (any specified strain or dose) used for the prevention of AAD in children. Thirty-three studies (6352 participants) were included. Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus spp., alone or in combination. The overall evidence suggested a moderate protective effect of probiotics for preventing AAD. Evidence also suggested that probiotics can moderately reduce the duration of diarrhea, a reduction by almost one day. Adverse event rates were low and no serious adverse events were attributable to probiotics. No serious adverse events were observed among both inpatient and outpatient children, including small studies conducted in the intensive care unit and in the neonatal unit. However, there were observational studies not included in this review reporting serious adverse events in severely debilitated or immunocompromised children with underlying risk factors including central venous catheter use and disorders associated with bacterial/fungal translocation.

Probiotics for gastrointestinal disorder: proposed recommendations for children of the Asia Pacific region

This paper published in 2017 proposed recommendations for the use of probiotics in different pediatric gastrointestinal diseases in the Asia-Pacific region. Epidemiology and clinical patterns of intestinal diseases in Asia-Pacific countries were discussed. Evidence-based recommendations and randomised controlled trials in the region were revised. The working group had proposed the following recommendations for pediatric intestinal diseases based on available data:

• Acute gastroenteritis: Probiotics can be considered in adjunct to oral rehydration therapy in children with acute gastroenteritis. This recommendation does not include children with severe malnutrition. At present, S. boulardii CNCM I-745 and L. rhamnosus GG are the two strains for which there is compelling evidence of efficacy. L.reuteri DSM 17938 may be considered albeit proof of efficacy is less consistent.
• Antibiotic-associated diarrhea: Probiotics may be considered on a case by case basis for the prevention of AAD. S. boulardii CNCM I-745 and L. rhamnosus GG are two strains for which the quality of evidence is good.
• C. difficile infection: Probiotics may be considered for the prevention of C. difficile-associated diarrhea. At present, the recommended strain is S. boulardii CNCM I-745 with which the quality of evidence is low.
• Prevention of nosocomial diarrhea: Probiotics may be considered to prevent hospital-acquired intestinal infections and diarrhea in children admitted to hospital. Although the evidence remains weak, L. rhamnosus GG is the strain recommended for this indication.
• Traveler’s diarrhea and Functional intestinal disorders: Data for the use of probiotics in preventing traveler’s diarrhea and functional intestinal disorders are insufficient.
• Infant colic: Probiotic administration may be considered for the treatment of infantile colic although the quality of evidence is weak. At present, the recommended strain is L. reuteri DSM 17938.
• Inflammatory bowel disease: There is no strong evidence supporting the treatment of IBD with probiotics. In pouchitis probiotic therapy may be considered based on evaluation of individual cases. At present, the recommended probiotic preparation is VSL#3 for which the quality of evidence is weak.
• H. pylori treatment: Probiotics may be considered for the prevention of side effects and improving eradication rates in children undergoing therapy for H. pylori. The recommended strains include S. boulardii CNCM I-745 and others for which the quality of evidence is weak.
• Necrotising enterocolitis (NEC): Probiotics may be considered for prevention of NEC in high-risk populations as there is evidence that the risk of NEC and the associated mortality may be reduced. However since there is no agreement on strains, indications and scheme, the decision should be taken in agreement with the parents, in the light of limited evidence.

Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19

Although COVID-19 is primarily a respiratory illness, there is mounting evidence to suggest that the GI tract is involved in this disease. Scientists from The Chinese University of Hong Kong had investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition would resolve with clearance of the SARS-CoV-2 virus.

In this two-hospital cohort study, scientists obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma.

Gut microbiome composition was significantly altered in patients with COVID-19 irrespective of whether patients had received medication (p<0.01). Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low after disease resolution. Moreover, this perturbed composition exhibited stratification with disease severity concordant with elevated concentrations of inflammatory cytokines and blood markers such as C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.

Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggested that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.

The anxiolytic effect of probiotics: A systematic review and meta analysis of clinical and preclinical literature

Probiotics have generated intensive research interest in mental illness. Nevertheless, the anxiolytic potential of probiotics remains unclear. The present systematic review and meta-analysis aimed to evaluate the clinical and preclinical (animal model) evidence regarding the effect of probiotic administration on anxiety. While preclinical (animal) studies suggest that probiotics may help reduce anxiety, such findings have not yet translated to clinical research in humans. Further investigation of probiotic treatment for clinically relevant anxiety is warranted, particularly with respect to the probiotic species L. rhamnosus.