Small intestinal bacterial overgrowth (SIBO) is an uprising gastrointestinal disorder affecting millions of individuals in the world. This symptom is defined by an excess and imbalance of small intestinal bacteria.[1] Symptoms of SIBO are abdominal distension, bloating, diarrhoea, gas formation, and other nonspecific issues overlapping with other gastrointestinal disorders. SIBO should be referred to as a symptom, because it always has a root cause, such as overuse of antibiotics, gastric acid suppression, dysmotility, gastric bypass, etc. Glucose and lactulose breath testing have become the standard diagnostic method thanks to their non-invasive nature and low cost, but a gold standard diagnostic remains a small bowel aspirate and culture. Treatment usually consists of a course of oral antibiotics in order to lessen the overgrowth.
Traditionally, the go-to antibiotics for treatment of SIBO are tetracyclines, fluoroquinolones, and co-trimoxazole. Rifaximin, a nonabsorbable antibiotic acting against Gram-positive and Gram-negative aerobic and anaerobic bacteria, has become popular against many clinicians for SIBO management. However, many studies show its effect isn´t as virtuous. In a recent meta-analysis investigating the effectiveness of rifaximin in bacterial overgrowth, the efficacy of rifaximin was 64% as compared to 41% with other systemic antibiotics, including tetracyclines and Metronidazole.[2] Another meta-analysis looking at eight studies showed that the effectiveness of rifaximin in the normalization rate of breath testing was 49.5%.[3] This causes some clinicians to rely on herbal antimicrobials for eradicating SIBO. What about probiotics? A popular belief it that probiotics can make SIBO worse. While that may be true[4] because of lactic acidosis, if correct strains are used, a promising outcome can be expected.
Probiotics
Probiotics are live microorganisms, which can help the symptoms of SIBO. They act by multiple mechanisms, such modulating the gut microbiota, sustaining the integrity of intestinal epithelium, upregulating anti-inflammatory cytokines and growth factors, producing short-chain and branched-chain fatty acids, as well as interacting with the brain-gut axis by regulating endocrine and neurologic functions.[5]
A recent meta-analysis shows that probiotics are effective in reducing SIBO and alleviating its symptoms. They may also enhance the effectiveness of antibiotics as demonstrated in a study where patients treated with rifaximin along with Lactobacillus Casei had greater improvement in their symptoms with dual therapy as opposed to antibiotics alone.[6]
When using probiotics, a GI map can be helpful as you know which bacteria you need to target. Bacteria typically connected to SIBO were investigated[7] and are the following:
-Streptococcus (71%; 6.4 ± 0.8),
-Escherichia coli (69%; 7.2 ± 0.9),
-Staphylococcus (25%; 6.2 ± 0.6),
-Micrococcus (22%; 6.0 ± 0.7),
-Klebsiella (20%; 7.1 ± 0.8),
-Proteus (11%; 6.1 ± 0.8)
for microaerophilic bacteria, and
-Lactobacillus (75%; 6.1 ± 1.1),
-Bacteroides (29%; 6.9 ± 1.3),
-Clostridium (25%; 5.5 ± 1.0),
-Veillonella (25%; 5.3 ± 0.7),
-Fusobacterium (13%; 4.8 ± 0.5),
-Peptostreptococcus (13%; 6.1 ± 0.7)
for anaerobic bacteria.
Other common bacteria include Salmonella, Shigella, Citrobacter, Enterobacter, and Yersinia, archaea are methanobrevibacter. Once you know which bacteria you´re dealing with, you can target them.
Here is a simple overview of probiotics and their effects:
- Bacillus subtilis
Supports gut repair by increasing IgA and butyrate
Secretes molecules which inhibit Staphylococcus aureus
Decreases Alistipes, Bacteroides, Odoribacter, Dehalobacterium, Escherichia coli and Sutterella
Increases Lactobacillus, Dorea, Ruminococcus, and Oscillospira
- Bacillus Coagulans
Makes antibiotic treatment more efficient
Suppresses Enterobacterales
Enhances butyrogenesis
- Bacillus Clausi
Eradicates SIBO in 47% patients in 30 days
- Lactobacillus Reuteri
Produces reuterin which prevents Clostridium difficile
Clears methanogens
Reduces Proteobacteria phylum, Escherichia coli, Salmonella spp., Cronobacter sakazakii, Klebsiella pneumoniae, Enterobacter aerogenes, Enterobacter cloacae, Serratia odorifera, Hafnia alvei, Klebsiella oxytoca, and Staphylococcaceae
- Lactobacillus Rhamnosus
o Reduces the effects on metabolism by Bilophila wadsworthia
o Reduces Escherchia coli and disrupts its biofilm
- Lactobacillus Plantarum
Reduces Shigella, Enterobacter, Klebsiella, Firmicutes, Actinobacteria, and Proteobacteria
Increases beneficial Bacteroides, Bifidobacterium, and Lactobacillus
- Lactobacillus Paracasei
Reduces inflammation in guts
Reduces Bacteroides, Clostridia and Parasutterel
Increases beneficial Bacteroidales _S24-7, Lachnospiraceae and Ruminococcaceae
- Sacharomyces Boulardii
Protective against Candida albicans
Has anti-inflammatory effects in the gut
Inactivates pathogenic toxins
Stimulates enterocyte (cells of the intestinal lining) maturation
Eradicates SIBO in 33% patients in 1 week
Makes antibiotic treatment more efficient
- Bifidobacterium Animalis ssp. lactis
Has a positive effect on immunoglobulin A (IgA) secretion
- Bifidobacterium Longum
Controls Klebsiella pneumoniae pulmonary infection and immunomodulation
- Bifidobacterium Bifidum
Decreases Escherichia-Shigella
Bacillus Subtilis is a soil-based probiotic, which supports gut repair by increasing IgA and butyrate. It secretes molecules that inhibit Staphylococcus aureus colonization. Staphylococcus aureus is an opportunistic human pathogen which can cause infections of the skin, wounds, soft tissues, bloodstream, bones, lungs, and gastrointestinal tract. From the gut, S. aureus can in principle reach other body sites through translocation across the mucosa and epithelium. Alternatively, S. aureus translocation may follow active damage of the epithelium through the secretion of inflammatory compounds, allergens or toxic products.
An oral probiotic containing live B. Subtilis spores eliminated[8] S. aureus from the guts of mice. This suggested that probiotics might decolonize S. aureus from the human gut without the risks that go with antibiotics. After four weeks of probiotic treatment in humans, S. aureus in stool declined by 97%. S. aureus in the nose declined by 65%. Between the effects on these two sites, the researchers estimated that probiotic treatment got rid of at least 95% of S. aureus in the human body.
B. Subtilis is capable of eliminating other bacteria such as Suterella. Suterella has been found to be mildly pro-inflammatory and some research suggests this is due to an ability to degrade IgA. A study[9] investigating the effect of Bacillus subtilis and Antibiotic Growth Promoters showed that B. Subtillis greatly altered intestinal microbiota by decreasing amounts of Alistipes, Bacteroides, Odoribacter, Dehalobacterium, and Sutterella and increasing amounts of Lactobacillus, Dorea, Ruminococcus, and Oscillospira.
In weaned piglets, B. Subtilis DSM25841 treatment reduced enterotoxigenic Escherichia coli (ETEC) F4 infection and decreased the risk of diarrhoea.[10] In general, Bacillus-based probiotic can reduce the severity of the virulent E. coli, decrease Enterobacterales and increase Lachnospiraceae.[11]
Bacillus Coagulans, another soil-based probiotic, helps the good bacteria colonize in your gut and has been studied in people with IBS, Crohn´s and ulcerative colitis. A study[12] on patients with SIBO, minocycline was administered followed by B. Coagulans in one group and no probiotics in the other. The group that received B. Coagulans reported relief from most symptoms and the post treatment breath tests showed 93.3% negative results, while the minocycline only group only reported relief from pain in 46.7% cases and a 66.7 % negative results.
As suggested above, B.Coagulans alone is able to destroy unwanted bacteria, as we can see in a study[13] where B. Coagulans SANK 70258 suppressed Enterobacterales and enhanced butyrogenesis in microbiota models.
Another study[14] using Bacillus Clausii to treat SIBO patients had 40 SIBO positive patients. They were given the B. Clausii probiotics three times daily for thirty days. One month after the probiotics ended, each patient retested for SIBO using the same glucose breath test. 47% of the patients had cleared SIBO confirmed by negative or normal breath tests. This further indicates that B. Coagulans can be fairly effective without the use of minocycline.
Perhaps the most studied and effective probiotic is Lactobacillus Reuteri.
Human-derived L. Reuteri is a probiotic that produces the antimicrobial compound reuterin known[15] to prevent C. difficile colonization of antibiotic-treated faecal microbial communities. Reuterin production by L. Reuteri is compatible as a therapeutic in a clinically relevant mode.
When administered four weeks, L. Reuteri was associated with a significant decrease [16] of mean CH4 production and a total disappearance of CH4 production was observed in 11/20 patients with constipation type SIBO. In this study, L.s Reuteri was able to clear methanogens.
In a study on people with cystic fibrosis, L. Reuteri DMS 17938 managed to reduce Proteobacteria phylum from 32.6% to 10%.[17] Another study showed a reduction of these bacteria after 1 months of L. Reuteri:[18]
- Diarrheagenic E. coli
- Salmonella spp.
- Cronobacter sakazakii
- Klebsiella pneumoniae
- Enterobacter aerogenes
- Enterobacter cloacae
- Serratia odorifera
- Hafnia alvei
- Klebsiella oxytoca
L. Reuteri KUB-AC5 possessed antimicrobial activity in reducing Salmonella contamination in live poultry.[19] In extremely low-birth-weight infants, L. Reuteri supplementation for one week resulted in a lower abundance of Enterobacterales and Staphylococcaceae.[20]
L. Rhamnosus CNCM I-3690 reverses[21] the effects on metabolism of Bilophila wadsworthia, which feeds on dietary lipids. It synergizes with high fat diet to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Administration of the probiotic L. Rhamnosus limits B. wadsworthia-induced immune and metabolic impairment. L. Rhamnosus GR-1 can also can kill E. coli and can disrupt biofilms produced by these microbes.[22]
Lactobacillus Plantarum can reduce the different members of the Enterobacteriaceae family.[23] It competes with pathogenic bacteria for space and it can reduce numbers of Shigella, Enterobacter and Klebsiella.
L.Plantarum increased[24] the content of beneficial bacteria, including Bacteroides, Bifidobacterium, and Lactobacillus, and reduced the content of harmful bacteria, including Firmicutes, Actinobacteria, Proteobacteria, and Enterobacterales.
Another study[25] aimed to investigate the effects of probiotic Lactobacillus Paracasei NL41 on inflammation and the gut microbiota of type 2 diabetic rats induced by high-fat diet showed that L. Paracasei not only the inflammatory status, but also the microbiome, by reducing harmful bacteria Bacteroides, Clostridia (specifically, Ruminococcus torques), and Parasutterel, and enriching beneficial Bacteroidales _S24-7, and the families Lachnospiraceae and Ruminococcaceae.
Sacharomyces Boulardii is protective against Candida albicans, can be taken alongside antibiotics, has anti-inflammatory effects in the gut and can inactivate pathogenic toxins and stimulate enterocyte (cells of the intestinal lining) maturation.
In a pilot clinical study[26] of 40 patients diagnosed with SIBO due to an autoimmune condition. the effects of S. boulardii on hydrogen production and SIBO eradication was assessed and compared with metronidazole. The patients were divided into 3 groups; one group were given metronidazole alone for 1 week, another group were given metronidazole with S. boulardii for 1 week and the third group were given S. boulardii alone for 1 week. Two months later, hydrogen breath tests were repeated. The group that achieved the best results was the metronidazole and S. boulardii group, with SIBO eradicated in 55% of participants at 2 months. S. boulardii therapy alone eradicated 33% which was better than the group given metronidazole alone with just 25% SIBO eradication.
Bifidobacterium spp. play an important role in regulating the intestinal immunity and intestinal barrier. Bifidobacterium animalis ssp. lactis HY8002, selected from eight Bifidobacterium strains by in vitro experimentation, had exceptional resistance to digestive tract conditions and high adhesion to intestinal epithelial cells and a positive effect on immunoglobulin A (IgA) secretion by Peyer’s patch cells.[27]
Bifidobacterium longum was able to control Klebsiella pneumoniae pulmonary infection and immunomodulation.[28]
Bifidobacterium bifidum ATCC 29521 exhibited a significant increase in the diversity of the gut microbiome, and a decrease in the abundance of the genus Escherichia-Shigella in mice.
Probiotic mixtures
While single strain probiotics are effective, many researches study their effect when used in combination with other probiotics or prebiotics.
Studies based on the use of the intestinal probiotics Lactobacillus Rhamnosus GG, Lactobacillus Reuteri, and Bifidobacterium have each reported achieving reduced levels of Streptococcus mutans. [29][30]
Lactobacillus Plantarum and Lactobacillus Rhamnosus were able to reduce[31] biofilm of Escherichia coli and Staphylococcus aureus. Both probiotics significantly reduced the culturability of E. coli and S. aureus biofilms, mainly after 24 h of exposure, with reduction percentages of 70% and 77% for L. plantarum and 76% and 63% for L. Rhamnosus.
Twenty-one healthy adult volunteers received a probiotic mixture once a day for 60 days containing probiotics L. Plantarum, L. Salivarius, L. Casei, L. Ccidophilus, B. Animalis subsp. lactis and B. Bifidum). The study found[32] that this probiotic intervention reduced the abundance of potential bacteria such as Citrobacter and Klebsiella in the human gut microbial community.
Mixed probiotics composed of three thermophilic lactic-acid-producing bacteria strains, L. Helveticus BGRA43 (strong proteolytic activity, antimicrobial activity, and adhesion to gut cell activity), L. Fermentum BGHI14 (immunomodulatory effect), and Streptococcus Thermophiles BGVLJ1–44 (strong proteolytic activity and immunomodulatory effect), influenced the colonization of piglet guts with beneficial bacteria, and reduced the number of Enterobacterales.[33]
In a randomized controlled trial[34] of healthy cats the administration of synbiotics (containing E. Faecium, B. Bifidum, E. Thermophilus, L. Acidophilus, L. Bulgaricus, L. Casei, and L. Plantarum). The relative abundance of Actinobacteria, Bacteroides, Prevotella, Ruminococcaceae, Veillonellaceae, and Erysipelotrichaceae decreased and relative abundance of Clostridiaceae and Proteobacteria increased during treatment. [35]
Oral daily supplementation with a combination of a prebiotic and probiotics B. Bifidum and L. Acidophilus for three weeks decreased the intestinal load of Enterobacterales among eight patients with long-term intestinal carriage.[36]
Bifidobacterium Animalis subsp. lactis BB-12 and Lactobacillus Reuteri DSM 17938 were the most effective single-strain probiotics against Escherichia coli, proving that most effective probiotics against E. coli strains are the lactic acid bacteria and bifidobacteria. The overall results from both in vitro tests reveal that all selected probiotics exhibited an antagonistic activity against all E. coli strains.[37]
Glycomacropeptide (GMP), a whey protein prebiotic, showed[38] a reduction from 30–35 to 7% in Desulfovibrio.
[2] Systematic review with meta‐analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth - PMC (nih.gov)
[4] Brain fogginess, gas and bloating: a link between SIBO, probiotics and metabolic acidosis - PMC (nih.gov)
[6] Effect of probiotic or prebiotic supplementation on antibiotic therapy in the small intestinal bacterial overgrowth: a comparative evaluation - PubMed (nih.gov)
[10] Bacillus sp. probiotic supplementation diminish the Escherichia coli F4ac infection in susceptible weaned pigs by influencing the intestinal immune response, intestinal microbiota and blood metabolomics - PMC (nih.gov)
[11] Evaluation of in ovo Bacillus spp. based probiotic administration on horizontal transmission of virulent Escherichia coli in neonatal broiler chickens - PMC (nih.gov)
[13] Bacillus coagulans SANK 70258 suppresses Enterobacteriaceae in the microbiota of ulcerative colitis in vitro and enhances butyrogenesis in healthy microbiota - PubMed (nih.gov)
[19] Protective effect of Lactobacillus reuteri KUB-AC5 against Salmonella Enteritidis challenge in chickens - PubMed (nih.gov)
[20] The Potential of Probiotics to Eradicate Gut Carriage of Pathogenic or Antimicrobial-Resistant Enterobacterales - PMC (nih.gov)
[30] https://www.nih.gov/news-events/nih-research-matters/probiotic-blocks-staph-bacteria-colonizing-people
[33] Promotion of Early Gut Colonization by Probiotic Intervention on Microbiota Diversity in Pregnant Sows - PMC (nih.gov)
[34] Effects of a synbiotic on the fecal microbiome and metabolomic profiles of healthy research cats administered clindamycin: a randomized, controlled trial - PMC (nih.gov)
[35] Effects of a synbiotic on the fecal microbiome and metabolomic profiles of healthy research cats administered clindamycin: a randomized, controlled trial - PMC (nih.gov)
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