Expanded question: What are the most common and beneficial probiotics in the human genome, their benefits, sources, and the pathological bacteria that can occur due to a lack of a healthy intestinal biome?

Answered on June 2, 2024
The most common and beneficial probiotics in the human gut microbiome include species from the genera Lactobacillus, Bifidobacterium, and Bacteroides. These probiotics play crucial roles in maintaining gut homeostasis and overall health.
Benefits:
1. Lactobacillus spp.: These bacteria produce lactic acid, which inhibits pathogenic bacteria, enhances gut barrier function, and modulates the immune system by promoting anti-inflammatory responses.[1-2]
2. Bifidobacterium spp.: They are involved in the fermentation of dietary fibers to produce short-chain fatty acids (SCFAs) like acetate and butyrate, which nourish colonocytes, maintain gut barrier integrity, and have anti-inflammatory effects.[3-4]
3. Bacteroides spp.: These bacteria metabolize complex polysaccharides, contributing to nutrient absorption and production of essential vitamins. They also play a role in maintaining gut eubiosis and preventing colonization by pathogens.[5-6]
Sources:
Lactobacillus spp.: Found in fermented foods such as yogurt, kefir, sauerkraut, and kimchi.
Bifidobacterium spp.: Present in fermented dairy products like yogurt and certain cheeses.
Bacteroides spp.: These are endogenous to the gut and are not typically consumed through diet but can be supported by a fiber-rich diet.
Pathological Bacteria Due to Dysbiosis:
Clostridioides difficile: Dysbiosis, particularly a reduction in beneficial bacteria like Bifidobacterium and Lactobacillus, can lead to overgrowth of C. difficile, causing severe colitis.[3]
Enteropathogenic Escherichia coli: A disrupted microbiome can facilitate the colonization and infection by pathogenic E. coli strains, leading to gastrointestinal diseases.
Salmonella spp.: Reduced competition from beneficial microbes can allow pathogenic bacteria like Salmonella to thrive, causing infections.
Maintaining a balanced gut microbiome through diet, probiotics, and prebiotics is essential for preventing dysbiosis and associated pathologies.

References

1.
Role of in Human Health and Diseases.

Mu Q, Tavella VJ, Luo XM.

Frontiers in Microbiology. 2018;9:757. doi:10.3389/fmicb.2018.00757. Copyright License: CC BY

() is a well-studied probiotic bacterium that can colonize a large number of mammals. In humans, is found in different body sites, including the gastrointestinal tract, urinary tract, skin, and breast milk. The abundance of varies among different individuals. Several beneficial effects of have been noted. First, can produce antimicrobial molecules, such as organic acids, ethanol, and reuterin. Due to its antimicrobial activity, is able to inhibit the colonization of pathogenic microbes and remodel the commensal microbiota composition in the host. Second, can benefit the host immune system. For instance, some strains can reduce the production of pro-inflammatory cytokines while promoting regulatory T cell development and function. Third, bearing the ability to strengthen the intestinal barrier, the colonization of may decrease the microbial translocation from the gut lumen to the tissues. Microbial translocation across the intestinal epithelium has been hypothesized as an initiator of inflammation. Therefore, inflammatory diseases, including those located in the gut as well as in remote tissues, may be ameliorated by increasing the colonization of . Notably, the decrease in the abundance of in humans in the past decades is correlated with an increase in the incidences of inflammatory diseases over the same period of time. Direct supplementation or prebiotic modulation of may be an attractive preventive and/or therapeutic avenue against inflammatory diseases.

2.

Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.

3.
Intestinal Microbiota in Health and Disease: Role of Bifidobacteria in Gut Homeostasis.

Tojo R, Suárez A, Clemente MG, et al.

World Journal of Gastroenterology. 2014;20(41):15163-76. doi:10.3748/wjg.v20.i41.15163.

The pool of microbes inhabiting our body is known as "microbiota" and their collective genomes as "microbiome". The colon is the most densely populated organ in the human body, although other parts, such as the skin, vaginal mucosa, or respiratory tract, also harbour specific microbiota. This microbial community regulates some important metabolic and physiological functions of the host, and drives the maturation of the immune system in early life, contributing to its homeostasis during life. Alterations of the intestinal microbiota can occur by changes in composition (dysbiosis), function, or microbiota-host interactions and they can be directly correlated with several diseases. The only disease in which a clear causal role of a dysbiotic microbiota has been demonstrated is the case of Clostridium difficile infections. Nonetheless, alterations in composition and function of the microbiota have been associated with several gastrointestinal diseases (inflammatory bowel disease, colorectal cancer, or irritable bowel syndrome), as well as extra-intestinal pathologies, such as those affecting the liver, or the respiratory tract (e.g., allergy, bronchial asthma, and cystic fibrosis), among others. Species of Bifidobacterium genus are the normal inhabitants of a healthy human gut and alterations in number and composition of their populations is one of the most frequent features present in these diseases. The use of probiotics, including bifidobacteria strains, in preventive medicine to maintain a healthy intestinal function is well documented. Probiotics are also proposed as therapeutic agents for gastrointestinal disorders and other pathologies. The World Gastroenterology Organization recently published potential clinical applications for several probiotic formulations, in which species of lactobacilli are predominant. This review is focused on probiotic preparations containing Bifidobacterium strains, alone or in combination with other bacteria, which have been tested in human clinical studies. In spite of extensive literature on and research into this topic, the degree of scientific evidence of the effectiveness of probiotics is still insufficient in most cases. More effort need to be made to design and conduct accurate human studies demonstrating the efficacy of probiotics in the prevention, alleviation, or treatment of different pathologies.

4.
Unraveling the Puzzle: Health Benefits of Probiotics-a Comprehensive Review.

Gul S, Durante-Mangoni E.

Journal of Clinical Medicine. 2024;13(5):1436. doi:10.3390/jcm13051436.

New Research

A growing number of probiotic-containing products are on the market, and their use is increasing. Probiotics are thought to support the health of the gut microbiota, which in turn might prevent or delay the onset of gastrointestinal tract disorders. Obesity, type 2 diabetes, autism, osteoporosis, and some immunological illnesses are among the conditions that have been shown to possibly benefit from probiotics. In addition to their ability to favorably affect diseases, probiotics represent a defense system enhancing intestinal, nutritional, and oral health. Depending on the type of microbial strain utilized, probiotics can have variable beneficial properties. Although many microbial species are available, the most widely employed ones are lactic acid bacteria and bifidobacteria. The usefulness of these bacteria is dependent on both their origin and their capacity to promote health. Probiotics represent a valuable clinical tool supporting gastrointestinal health, immune system function, and metabolic balance. When used appropriately, probiotics may provide benefits such as a reduced risk of gastrointestinal disorders, enhanced immunity, and improved metabolic health. Most popular probiotics, their health advantages, and their mode of action are the topic of this narrative review article, aimed to provide the reader with a comprehensive reappraisal of this topic matter.

5.
Gut Bacteroides Species in Health and Disease.

Zafar H, Saier MH.

Gut Microbes. 2021 Jan-Dec;13(1):1-20. doi:10.1080/19490976.2020.1848158. Copyright License: CC BY

Leading Journal

The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host. However, beneficial gut organisms can also be pathogenic when present in the gut or other locations in the body. Among dominant beneficial bacteria are several species of Bacteroides, which metabolize polysaccharides and oligosaccharides, providing nutrition and vitamins to the host and other intestinal microbial residents. These topics and the specific organismal and molecular interactions that are known to be responsible for the beneficial and detrimental effects of Bacteroides species in humans comprise the focus of this review. The complexity of these interactions will be revealed.

6.
Bacteroides and Related Species: The Keystone Taxa of the Human Gut Microbiota.

Shin JH, Tillotson G, MacKenzie TN, et al.

Anaerobe. 2024;85:102819. doi:10.1016/j.anaerobe.2024.102819.

New Research

Microbial communities play a significant role in maintaining ecosystems in a healthy homeostasis. Presently, in the human gastrointestinal tract, there are certain taxonomic groups of importance, though there is no single species that plays a keystone role. Bacteroides spp. are known to be major players in the maintenance of eubiosis in the human gastrointestinal tract. Here we review the critical role that Bacteroides play in the human gut, their potential pathogenic role outside of the gut, and their various methods of adapting to the environment, with a focus on data for B. fragilis and B. thetaiotaomicron. Bacteroides are anaerobic non-sporing Gram negative organisms that are also resistant to bile acids, generally thriving in the gut and having a beneficial relationship with the host. While they are generally commensal organisms, some Bacteroides spp. can be opportunistic pathogens in scenarios of GI disease, trauma, cancer, or GI surgery, and cause infection, most commonly intra-abdominal infection. B. fragilis can develop antimicrobial resistance through multiple mechanisms in large part due to its plasticity and fluid genome. Bacteroidota (formerly, Bacteroidetes) have a very broad metabolic potential in the GI microbiota and can rapidly adapt their carbohydrate metabolism to the available nutrients. Gastrointestinal Bacteroidota species produce short-chain fatty acids such as succinate, acetate, butyrate, and occasionally propionate, as the major end-products, which have wide-ranging and many beneficial influences on the host. Bacteroidota, via bile acid metabolism, also play a role in in colonization-resistance of other organisms, including Clostridioides difficile, and maintenance of gut integrity.

Expanded question: How do dietary changes impact the effectiveness of probiotics, particularly in relation to the common and beneficial probiotics such as Lactobacillus spp., Bifidobacterium spp., and Bacteroides spp.?

Answered on June 2, 2024
Dietary changes significantly impact the effectiveness of probiotics, particularly for common and beneficial probiotics such as Lactobacillus spp., Bifidobacterium spp., and Bacteroides spp.. The interaction between diet and probiotics can influence the survival, persistence, and functional outcomes of these microorganisms in the gut.
Lactobacillus spp.:
High-Fat, High-Sugar Diets (HFHSD): Studies indicate that Lactobacillus plantarum persistence is significantly improved in mice fed HFHSD compared to low-fat, plant-polysaccharide-rich diets (LFPPD). This suggests that a Western diet may enhance the survival of certain Lactobacillus strains.[1]
Dietary Fiber: High-fiber diets support the growth and activity of Lactobacillus by providing fermentable substrates that these bacteria utilize to produce beneficial metabolites like short-chain fatty acids (SCFAs).[2]
Bifidobacterium spp.:
Dietary Fiber: Bifidobacteria thrive on dietary fibers, which they ferment to produce SCFAs. High-fiber diets are associated with increased abundance and activity of Bifidobacterium.[3]
Western Diets: High-fat diets can disrupt gut microbiota composition, but supplementation with Bifidobacterium can help mitigate these effects by promoting beneficial microbial populations and improving metabolic outcomes.[4]
Bacteroides spp.:
Complex Polysaccharides: Bacteroides species are adept at degrading complex polysaccharides found in plant-based diets. Diets rich in diverse fibers support the growth and metabolic activity of Bacteroides.[5]
Pathological Bacteria Due to Dysbiosis:
Clostridioides difficile: Dysbiosis, often resulting from low-fiber, high-fat diets, can lead to overgrowth of pathogenic bacteria like C. difficile.[4]
Enteropathogenic Escherichia coli and Salmonella spp.: A disrupted microbiome due to poor dietary habits can facilitate colonization by these pathogens, leading to gastrointestinal infections.[2]
In summary, dietary patterns play a crucial role in modulating the effectiveness of probiotics. High-fiber diets generally support the growth and activity of beneficial probiotics, while high-fat, high-sugar diets may enhance the persistence of certain strains but can also disrupt overall gut microbiota balance.

References

1.
Dietary Perturbations Alter the Ecological Significance of Ingested Lactobacillus Plantarum in the Digestive Tract.

Yin X, Lee B, Zaragoza J, Marco ML.

Scientific Reports. 2017;7(1):7267. doi:10.1038/s41598-017-07428-w. Copyright License: CC BY

Host diet is a major determinant of the composition and function of the intestinal microbiome. Less understood is the importance of diet on ingested strains with probiotic significance. We investigated the population dynamics of exogenous Lactobacillus plantarum and its interactions with intestinal bacteria in mice undergoing switches between high-fat, high-sugar (HFHSD) and low-fat, plant-polysaccharide rich (LFPPD) diets. The survival and persistence of ingested L. plantarum WCFS1 was significantly improved during mouse consumption of HFHSD and was negatively associated with the numbers of indigenous Lactobacillus species. Diet also rapidly changed the composition of the indigenous microbiota, but with some taxa differentially affected between HFHSD periods. L. plantarum was not integrated into indigenous bacterial community networks according to co-occurrence patterns but still conferred distinct effects on bacterial species diversity and microbiota stability largely in a diet-dependent manner. Metagenome predictions supported the premise that L. plantarum dampens the effects of diet on the microbiome. This strain also consistently altered the predicted genetic content in the distal gut by enriching for genes encoding glyosyltransferases and bile salt hydrolases. Our findings demonstrate the interactions between ingested, transient probiotic bacteria and intestinal bacterial communities and how they can differ depending on host diet.

2.
Modulation of Gut-Microbiota Through Probiotics and Dietary Interventions to Improve Host Health.

Dasriya VL, Samtiya M, Ranveer S, et al.

Journal of the Science of Food and Agriculture. 2024;. doi:10.1002/jsfa.13370.

New Research

Dietary patterns play an important role in regards to the modulation and control of the gut microbiome composition and function. The interaction between diet and microbiota plays an important role in order to maintain intestinal homeostasis, which ultimately affect the host's health. Diet directly impacts the microbes that inhabit the gastrointestinal tract (GIT), which then contributes to the production of secondary metabolites, such as short-chain fatty acids, neurotransmitters, and antimicrobial peptides. Dietary consumption with genetically modified probiotics can be the best vaccine delivery vector and protect cells from various illnesses. A holistic approach to disease prevention, treatment, and management takes these intrinsically linked diet-microbes, microbe-microbe interactions, and microbe-host interactions into account. Dietary components, such as fiber can modulate beneficial gut microbiota, and they have resulting ameliorative effects against metabolic disorders. Medical interventions, such as antibiotic drugs can conversely have detrimental effects on gut microbiota by disputing the balance between Bacteroides and firmicute, which contribute to continuing disease states. We summarize the known effects of various dietary components, such as fibers, carbohydrates, fatty acids, vitamins, minerals, proteins, phenolic acids, and antibiotics on the composition of the gut microbiota in this article in addition to the beneficial effect of genetically modified probiotics and consequentially their role in regards to shaping human health. © 2024 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

3.
Bifidobacterium Spp. As Functional Foods: A Review of Current Status, Challenges, and Strategies.

He BL, Xiong Y, Hu TG, Zong MH, Wu H.

Critical Reviews in Food Science and Nutrition. 2023;63(26):8048-8065. doi:10.1080/10408398.2022.2054934.

Leading Journal

Members of Bifidobacterium are among the first microbes to colonize the human intestine naturally, their abundance and diversity in the colon are closely related to host health. Recently, the gut microbiota has been gradually proven to be crucial mediators of various metabolic processes between the external environment and the host. Therefore, the health-promoting benefits of Bifidobacterium spp. and their applications in food have gradually been widely concerned. The main purpose of this review is to comprehensively introduce general features, colonization methods, and safety of Bifidobacterium spp. in the human gut, highlighting its health benefits and industrial applications. On this basis, the existing limitations and scope for future research are also discussed. Bifidobacteria have beneficial effects on the host's digestive system, immune system, and nervous system. However, the first prerequisite for functioning is to have enough live bacteria before consumption and successfully colonize the colon after ingestion. At present, strain breeding, optimization (e.g., selecting acid and bile resistant strains, adaptive evolution, high cell density culture), and external protection technology (e.g., microencapsulation and protectants) are the main strategies to address these challenges in food application.

4.
Modulation of Gut Microbiota During Probiotic-Mediated Attenuation of Metabolic Syndrome in High Fat Diet-Fed Mice.

Wang J, Tang H, Zhang C, et al.

The ISME Journal. 2015;9(1):1-15. doi:10.1038/ismej.2014.99.

Leading Journal

Structural disruption of gut microbiota and associated inflammation are considered important etiological factors in high fat diet (HFD)-induced metabolic syndrome (MS). Three candidate probiotic strains, Lactobacillus paracasei CNCM I-4270 (LC), L. rhamnosus I-3690 (LR) and Bifidobacterium animalis subsp. lactis I-2494 (BA), were individually administered to HFD-fed mice (10(8) cells day(-1)) for 12 weeks. Each strain attenuated weight gain and macrophage infiltration into epididymal adipose tissue and markedly improved glucose-insulin homeostasis and hepatic steatosis. Weighted UniFrac principal coordinate analysis based on 454 pyrosequencing of fecal bacterial 16S rRNA genes showed that the probiotic strains shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean mice fed a normal (chow) diet. Redundancy analysis revealed that abundances of 83 operational taxonomic units (OTUs) were altered by probiotics. Forty-nine altered OTUs were significantly correlated with one or more host MS parameters and were designated 'functionally relevant phylotypes'. Thirteen of the 15 functionally relevant OTUs that were negatively correlated with MS phenotypes were promoted, and 26 of the 34 functionally relevant OTUs that were positively correlated with MS were reduced by at least one of the probiotics, but each strain changed a distinct set of functionally relevant OTUs. LC and LR increased cecal acetate but did not affect circulating lipopolysaccharide-binding protein; in contrast, BA did not increase acetate but significantly decreased adipose and hepatic tumor necrosis factor-α gene expression. These results suggest that Lactobacillus and Bifidobacterium differentially attenuate obesity comorbidities in part through strain-specific impacts on MS-associated phylotypes of gut microbiota in mice.

5.
Genomic and Metabolic Studies of the Impact of Probiotics on a Model Gut Symbiont and Host.

Sonnenburg JL, Chen CT, Gordon JI.

PLoS Biology. 2006;4(12):e413. doi:10.1371/journal.pbio.0040413. Copyright License: CC BY

Leading Journal

Probiotics are deliberately ingested preparations of live bacterial species that confer health benefits on the host. Many of these species are associated with the fermentation of dairy products. Despite their increasing use, the molecular details of the impact of various probiotic preparations on resident members of the gut microbiota and the host are generally lacking. To address this issue, we colonized germ-free mice with Bacteroides thetaiotaomicron, a prominent component of the adult human gut microbiota, and Bifidobacterium longum, a minor member but a commonly used probiotic. Simultaneous whole genome transcriptional profiling of both bacterial species in their gut habitat and of the intestinal epithelium, combined with mass-spectrometric analysis of habitat-associated carbohydrates, revealed that the presence of B. longum elicits an expansion in the diversity of polysaccharides targeted for degradation by B. thetaiotaomicron (e.g., mannose- and xylose-containing glycans), and induces host genes involved in innate immunity. Although the overall transcriptome expressed by B. thetaiotaomicron when it encounters B. longum in the cecum is dependent upon the genetic background of the mouse (as assessed by a mixed analysis of variance [ANOVA] model of co-colonization experiments performed in NMRI and C57BL/6J animals), B. thetaiotaomicron's expanded capacity to utilize polysaccharides occurs independently of host genotype, and is also observed with a fermented dairy product-associated strain, Lactobacillus casei. This gnotobiotic mouse model provides a controlled case study of how a resident symbiont and a probiotic species adapt their substrate utilization in response to one another, and illustrates both the generality and specificity of the relationship between a host, a component of its microbiota, and intentionally consumed microbial species.

Expanded question: Discuss and elaborate on the following: What are the key benefits of the probiotic Saccharomyces Boulardii Probiotics + MOS 5 Billion CFU Probiotic Yeast for Intestinal Health? There are reports that this probiotic can suppress the recurrence of Clostridioides difficile (CDiF) enteritis. Are there studies to support this? From my personal experience, I have seen several patients with recurrent CDiF who have avoided recurrence of this illness.

Answered on June 2, 2024
Saccharomyces boulardii (S. boulardii) is a probiotic yeast with several key benefits for intestinal health, particularly in the context of Clostridioides difficile (C. difficile) infection (CDI).
Key Benefits:
1. Inhibition of Pathogens: S. boulardii produces proteases that inactivate C. difficile toxins A and B, reducing their pathogenicity.
2. Immune Modulation: It enhances the immune response by increasing the production of secretory IgA and modulating cytokine production.
3. Gut Barrier Function: S. boulardii helps maintain and restore the integrity of the intestinal barrier, reducing permeability and preventing translocation of pathogens.
Evidence for CDI Recurrence Prevention:
Several studies support the use of S. boulardii in preventing recurrent CDI:
• A multicenter double-blind RCT demonstrated a significant reduction in CDI recurrence when S. boulardii was used alongside metronidazole or vancomycin in patients with a history of recurrent CDI (RR 0.43, 34.6% with S. boulardii vs. 64.7% with placebo).[1]
• A follow-up study showed benefits in a subgroup treated with high-dose vancomycin and S. boulardii, with a recurrence rate of 16.7% compared to 50% with placebo.[1]
• A controlled prospective intervention study indicated that S. boulardii significantly reduced CDI rates in hospitalized patients receiving antibiotics (OR = 0.06, 95% CI 0.02-0.16).[2]
Dosage:
The typical dosage used in clinical studies is 1 g/day, which corresponds to approximately 5 billion CFU, administered in divided doses.[1-2]
Guideline Recommendations:
The American College of Gastroenterology (ACG) guidelines acknowledge the potential role of S. boulardii in preventing recurrent CDI, particularly in patients with a history of recurrence.[1]
In summary, S. boulardii has demonstrated efficacy in reducing the recurrence of CDI, particularly when used in conjunction with standard antibiotic therapy in patients with a history of recurrent infections.

References

1.
ACG Clinical Guidelines: Prevention, Diagnosis, and Treatment of Clostridioides Difficile Infections.

Kelly CR, Fischer M, Allegretti JR, et al.

The American Journal of Gastroenterology. 2021;116(6):1124-1147. doi:10.14309/ajg.0000000000001278.

A meta-analysis by McFarland et al. looked specifically at trials of a particular probiotic combination comprising 3 lactobacilli strains (Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus rhamnosus; Bio-K+) with in vitro activity against C. difficile (33). Of the 3 RCTs, only one showed efficacy of this mixture for primary prevention of CDI. This was a Chinese trial of elderly patients being treated with antibiotics in which the background incidence of CDI was extremely high (nearly 24%) (34), a rate uncommon in most healthcare settings. More recently, a meta-analysis of 19 RCTs concluded that probiotics were helpful at prevention of CDI in hospitalized patients if given closer to start of antibiotics, with a 70% lower risk if probiotics were started within 2 days but falling to a 30% risk reduction if probiotics were started after 2 days of antibiotic therapy (35). It is notable that these studies had extensive exclusion criteria including patients who were immunocompromised, undergoing cancer treatments, in an intensive care unit (ICU), or who had preexisting gastrointestinal (GI) conditions.
The PICO trial, published in 2017, randomized 33 patients with an initial mild-to-moderate CDI to 28 days of a 4-strain probiotics or placebo in addition to anti-CDI therapy and showed no difference in the rate of CDI recurrence (36). Saccharomyces boulardii is yeast that grows on lychee fruit and produces a protease that inactivates the receptor site for C. difficile toxin A, lending biologic plausibility to its use in CDI. Results from a multicenter double-blind RCT published in 1994 showed decreased CDI recurrence in patients treated with S. boulardii in addition to either metronidazole or vancomycin in those who had already experienced a recurrent episode (RR 0.43, 34.6% with S. boulardii vs 64.7% with placebo) (37). There was no benefit over placebo in patients who were being treated for an initial CDI. The authors' follow-up study, published in 2000, enrolled 168 patients with recurrent CDI who were treated with a 28-day course of S. boulardii or placebo in addition to anti-CDI therapy (38). The benefits in this study were limited to the subgroup that was treated with high-dose vancomycin and S. boulardii (16.7% recurrence vs 50% with placebo). The study was small, with 32 patients in the high-dose vancomycin group; thus, no firm conclusions could be drawn. Unfortunately, a planned larger trial was never conducted, and the benefits of S. boulardii for secondary prevention remain uncertain. A Cochrane review of probiotics for treatment of CDI, which included 4 studies, concluded that there is insufficient evidence to support a role for probiotics in treatment of CDI (39).

2.
Use of Prophylactic Saccharomyces Boulardii to Prevent Clostridium Difficile Infection in Hospitalized Patients: A Controlled Prospective Intervention Study.

Carstensen JW, Chehri M, Schønning K, et al.

European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology. 2018;37(8):1431-1439. doi:10.1007/s10096-018-3267-x.

Clostridium difficile infection (CDI) is a common complication to antibiotic use. Saccharomyces boulardii has shown effect as a prophylactic agent. We aimed to evaluate the efficacy of S. boulardii in preventing CDI in unselected hospitalized patients treated with antibiotics. We conducted a 1 year controlled prospective intervention study aiming to prescribe Sacchaflor (S. boulardii 5 × 10, Pharmaforce ApS) twice daily to hospitalized patients treated with antibiotics. Comparable departments from three other hospitals in our region were included as controls. All occurrences of CDI in patients receiving antibiotics were reported and compared to a baseline period defined as 2 years prior to intervention. Results were analyzed using run chart tests for non-random variation in CDI rates. In addition, odds ratios for CDI were calculated. S. boulardii compliance reached 44% at the intervention hospital, and 1389 patients were treated with Sacchaflor. Monthly CDI rates dropped from a median of 3.6% in the baseline period to 1.5% in the intervention period. S. boulardii treatment was associated with a reduced risk of CDI at the intervention hospital: OR = 0.06 (95% CI 0.02-0.16). At two control hospitals, CDI rates did not change. At one control hospital, the median CDI rate dropped from 3.5 to 2.4%, possibly reflecting the effects of simultaneous multifaceted intervention against CDI at that hospital. The results from this controlled prospective interventional study indicate that S. boulardii is effective for the prevention of CDI in an unselected cohort of mainly elderly patients from departments of internal medicine.