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. 2023 Oct 1;15(10):e46314. doi: 10.7759/cureus.46314

Unique Properties of Yeast Probiotic Saccharomyces boulardii CNCM I-745: A Narrative Review

Sarath Gopalan 1, Sridhar Ganapathy 2, Monjori Mitra 3, Neha 4,✉, Devesh Kumar Joshi 4, Krishna C Veligandla 5, Rahul Rathod 6, Bhavesh P Kotak 5
Editors: Alexander Muacevic, John R Adler
PMCID: PMC10621882  PMID: 37927652

Abstract

Probiotics, both bacterial and yeast, have long been associated with a beneficial health history and human well-being. Among yeasts, Saccharomyces is a genus that is efficacious in rendering better human health, with Saccharomyces boulardii (S. boulardii) CNCM I-745 being classified as a probiotic agent. The present review highlights the unique properties of S. boulardii and its rolein the prevention of antibiotic-associated diarrhea (AAD) and pediatric acute gastroenteritis (PAGE) in comparison to bacterial probiotics. Its unique properties,such as viability over a wide pH range, inability to acquire antibiotic resistance genes, and property to achieve a steady state rapidly, have given S. boulardii an edge over bacterial probiotics. In AAD patients, prophylactic use of S. boulardii has shown a significantly lower risk of AAD (in comparison to controls) and restored the diversity of gut microbiota. Among Indian children with PAGE, S. boulardii CNCM I-745 was found superior to Lactobacillus rhamnosus GG and four strains of Bacillus clausii in shortening the duration of diarrhea and reducing the length of hospital stay. S. boulardii CNCM I-745 being considered a safe probiotic for use in children and adults also finds recommendations in several international guidelines for the management of acute diarrhea. The current review discusses evidence for the proven efficacy and safety of S. boulardii CNCM I-745 as a probiotic for preventing gastrointestinal disorders.

Keywords: cncm i-745, paediatric acute gastroenteritis, antibiotic-associated diarrhoea, saccharomyces boulardii, probiotic

Introduction and background

The gut microbiome is invoked as a contributor to gastrointestinal (GI) ailments and a broad range of chronic human conditions, including cancer and diseases with inflammatory, metabolic, cardiovascular, autoimmune, neurologic, and psychiatric components [1,2]. Microbial dysbiosis is an imbalance of the structure and function of the gut intestinal microbiota, which is quite common in today’s World. Changes in diet, bacterial infections, and indiscriminate use of antibiotics are the common causes of dysbiosis [3].

One of the most efficient ways to restore gut microbial balance is probiotics [3]. Probiotic is a Greek term meaning “for life”. It is defined by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO) as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" [4,5]. There has been abundant research with probiotics of bacterial origin but limited work with probiotics of yeast origin. One of the rising threats of concern with probiotics of bacterial origin is their capability to transfer the resistant gene to pathogenic bacteria. This is where yeasts, which are naturally resistant to antibacterial agents, play a useful and important role as probiotics [6]. The other advantages of probiotics of yeast origin are demonstrated in Figure 1.

Figure 1. Advantages of yeasts as probiotics.

Figure 1

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 Adapted from Shruthi et al., 2022 [6] (CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/))

The yeast S. boulardii CNCM I-745 was the first yeast probiotic that was studied for the management of clinical disorders in humans. The S. boulardii strain is stable over a wide range of temperature levels and pH (including acidic conditions). It does not promote antibiotic resistance and has a beneficial effect against infections caused by pathogenic bacteria (e.g., Clostridium difficile, Salmonella, Shigella, Escherichia coli), viruses, and yeasts (mainly Candida albicans). Evidence supports the use of S. boulardii CNCM I-745 for treating several diseases [7].

The present review summarizes the current evidence on the role of S. boulardii as a biotherapeutic agent for the prevention of various GI diseases like antibiotic-associated diarrhea (AAD) and gut dysbiosis.

Review

PubMed and NCBI databases were used for the search of the articles using the following keywords: probiotics, yeast as probiotics, and advantages of probiotics.

Open-access articles discussing the advantages of various yeast strains as probiotics were included in the review.

History of probiotics

Elie Metchnikoff, a Nobel laureate, was the first to report the beneficial effect of probiotics on human health. He suggested that lactobacilli may be considered a probiotic with a positive impact on health and the prevention of aging [4].

Beneficial effects of probiotics on human health

Some beneficial effects of probiotics on human health are mentioned in Figure 2.

Figure 2. Some beneficial effects of probiotics on human health .

Figure 2

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Adapted from Celebioglu et al., 2018 [8]. (Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/))

GI: Gastrointestinal

Sources of probiotics

Probiotic bacteria have been obtained from a variety of sources, including human breast milk, diets containing both plants and meat, human and animal feces, and animal guts [9]. Another source of probiotics is the human GI tract. From this source, several of the probiotic strains such as Lactobacillus gasseri and L. reuteri used today have been isolated. Besides, many animal species, including pigs, rats, and even poultry, have intestines that are rich in probiotics [10]. Also, several bacterial, fungal, and archaeal species are abundantly found in the human microbiome [11].

Properties of an ideal probiotic

The probiotic strains act differently against different pathogens by various actions. They act by directly killing or inhibiting specific pathogens, destroying pathogenic toxins, and reinforcing the host cell integrity. They also prevent the attachment of pathogen-host cells, restore the normal microflora, and balance the immune response (up or down-regulation).

All probiotics do not possess all of these mechanisms, but probiotics, such as S. boulardii CNCM I-745, are found to possess multiple anti-pathogen properties [12,13]. S. boulardii possesses several mechanisms of action (Figure 2) which can be divided into three main types, namely, luminal action, trophic action, and mucosal-anti-inflammatory signaling effects. S. boulardii in the intestinal lumen, might aid in interfering with pathogenic toxins and their attachment, interacting with normal microbiota, preserving cellular physiology, or re-establishing short-chain fatty acid levels. In addition, S. boulardii may also regulate the immune system, both within the lumen and systemically [14].

Yeast as a probiotic

Yeast probiotics with some unique properties have an edge over bacterial probiotics and the differences between them are listed in Table 1.

Table 1. Difference between bacteria and yeast and its implication on probiotics .

PPM: Phosphopeptidomannan; PLM: Phospholipomannan; LPS: Lipopolysaccharide; LTA: Lipoteichoic acid

  Yeast Bacteria
Cell size [15] 10 µm 1 µm
Cell wall [15] Chitin, mannose (PPM, PLM), glucan Peptidoglycan, LPS (Gram-negative), LTA (Gram-positive)
Optimal growth conditions-pH [15] 4.5–6.5 6.5–7.5
Temperature (0C) [15] 20–30 10–80
Resistance to antibiotics [15] Yes No
Transmission of genetic material [15] No Yes
Autoaggregation [16] Yes Limited
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Possible implications of the difference between yeast and bacterial probiotic properties

The difference between yeast and bacterial probiotic properties and their possible implications are mentioned in Table 2.

Table 2. Possible implications of the difference between yeast and bacterial probiotic properties.

GI: Gastrointestinal

Properties Comments
Steric hindrance [16]   Yeast cells, due to their ~10 times larger size than bacteria, provide a steric hindrance against pathogenic bacteria. It increases the prospect of yeast being a probiotic agent
Immune response [17]   The cells of yeast contain many immunomodulatory components The outer layer of the cell wall consists of Mannoproteins that bind dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN), Toll-like receptor 4 (TLR4), and others The middle layer contains β-glucans which bind Dectin-1 and TLRs 2 and 6 The innermost wall layer contains chitin, which binds the mannose receptor
Different sites of action in the GI tract [15]   Yeast is found both in the stomach and colon, suggesting their ability to survive in such different conditions (resistance to pH variation, tolerance of stress). This suggests that yeast is a good candidate as a probiotic because probiotics entering the GI tract must be resistant to variations in the pH
Resistance to antibiotics [15]   Bacteria can transfer the resistance genes to pathogenic bacteria, leading to antibiotic resistance transfer of genetic material which is not possible between bacteria and yeast, making yeast a potential candidate as a probiotic for the prevention of antibiotic resistance
Autoaggregation[16]   The ability of yeast strains to self-aggregate and produce flocs is the autoaggregation property This is a survival response in the presence of adverse environmental conditions like the human GI tract This provides a competitive advantage to the yeast cell over other microorganisms, including enteric bacteria Because, as compared to the bacteria, the yeast cells are larger and heavier, they sediment faster and in a larger amount
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Properties of S. boulardii CNCM I‑745

S. boulardii CNCM I-745 is a probiotic yeast of choice for the management of AAD and pediatric acute gastroenteritis (PAGE). Henri Boulard (French microbiologist) discovered S. boulardii CNCM I-745 in 1923, and it belongs to the S. cerevisiae species [18]. Due to its ability to produce different bioactive compounds, S. boulardii has taken a key position in the scientific community and is recently being used for managing gut diseases. Clinical evidence suggests that oral administration of S. boulardii is beneficial in managing multiple GI diseases including traveler’s diarrhea, AAD, C. difficile-associated syndrome, irritable bowel syndrome, and Crohn’s disease [19]. Due to the excessive use of antimicrobials, a continuous rise in multidrug-resistant organisms is reported. Therefore, in managing antibiotic resistance, probiotics, especially S. boulardii, can be used as an adjunct to the management of infections [19]. The unique properties of S. boulardii are mentioned in Figure 3 [20,21].

Figure 3. Unique properties of S. boulardii CNCM I-745.

Figure 3

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Image Credits: All authors

Mechanism of action of S. boulardii as a probiotic

The gut microbiome performs a variety of functions, such as preventing pathogen colonization, maintaining the epithelial barrier, and controlling immune response [22]. S. boulardii similarly as a part of its probiotic effect has various modes of action like immunological and anti-toxin effects, modulation of intestinal flora, and impact on enzyme activity (Figure 4) [22].

Figure 4. Different potential mechanisms of action of Saccharomyces boulardii.

Figure 4

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Image Credits: All authors

On the left various effects of different pathogenic microbes are shown. On the right, seven different protective effects of S. boulardii are mentioned. Within the lumen of the intestine, S. boulardii may degrade toxins of pathogens, interfere with pathogenic adherence, modulate normal microbiota, and preserve normal intestinal physiology. S. boulardii may also indirectly restore normal SCFA balance and increase secretory IgA levels or act as an immune regulator by influencing cytokine levels.

LPS: Lipopolysaccharide; Sb: S. boulardii.

Clinical benefits of S. boulardii as a probiotic in AAD and PAGE

Clinical evidence demonstrating the role of S. boulardii in the management of AAD and PAGE is given in Table 3.

Table 3. S. boulardii in the management of AAD and PAGE.

AAD: Antibiotic-associated diarrhea; PAGE: Pediatric acute gastroenteritis

Study/design Population Intervention Results
S. boulardii for the prevention of AAD
McFarland et al./ Meta-analysis, 10 randomized controlled trials (RCTs) [14] Adults on antibiotics (n = 1869) S. boulardii (200 mg – 1000 mg /day) A significant therapeutic efficacy of S. boulardii in preventing AAD was reported (RR = 0.47, 95% CI: 0.35-0.63, P<0.001)
McFarland et al./ Meta-analysis 22 trials (23 treatment arms) [23] Children (n = 4155) on antibiotics Twelve trials tested a single strain of probiotic and 10 trials tested a mixture of probiotic strains Analysis among single strains trials (12 trials) showed that S. boulardii significantly reduced AAD (pooled RR = 0.43, 95% CI: 0.32-0.60). All the probiotics were safe
Jindal et al./ Randomised, open, parallel study [24] Children (n = 300, age 6 months-12 years) with upper respiratory tract infection or urinary tract infection receiving antibiotics Control group: Antibiotic test group: Antibiotic + S. boulardii [BASE] 250 mg B.D. A significant reduction in the incidence of diarrhea was observed in patients who received S. boulardii (P<0.001)
Szajewska et al./ Systematic review with meta-analysis, 21 RCTs [25] Children and adults (n = 4780) receiving antibiotics for any reason, including Helicobacter pylori eradication therapy   Control group: Antibiotic + placebo/no treatment   Experimental group: Antibiotic + S. boulardii at any dose/ duration Among patients treated with antibiotics, a reduced risk of AAD was observed in the S. boulardii group vs placebo or no treatment, from 18.7% to 8.5%   S. boulardii reduced the risk of diarrhea in children from 20.9% to 8.8% and in adults from 17.4% to 8.2%   In children, S. boulardii also reduced the risk of C. difficile-associated diarrhea  
Yang et al./ Meta-analysis, 21 studies[26] Children (n = 3534 patients) on antibiotics  S. boulardii For the prevention of AAD, the S. boulardii group could significantly reduce the diarrhea rate vs the control group   In a Meta-analysis of 7 studies (523 patients), the S. boulardii group demonstrated a significantly higher efficacy rate in preventing AAD vs the control group
S. boulardii for the management of PAGE
Padayachee et al./ Systematic review = 10 studies; Meta-analysis, 5 RCTs[27] Infants and children (n = 619, aged <16 years) with a diagnosis of acute gastroenteritis (≥3 unformed stools in the last 24 h and of ≤48 h duration) S. boulardii (250-500 mg/day) vs other treatments S. boulardii significantly reduced the duration of diarrhea compared with control (MD –0.57; 95% CI –0.83 to –0.30; n = 548 children; 5 studies) and had a statistically significant effect on stool frequency on days 1, 2, 3 and 4 (P = 0.001)   At the end of day 7, all children had solid stools
Szajewska et al./ Systemic review and Meta-analysis, 29 RCTs[28] Children (n = 4217, aged 1 month to 15 years) S. boulardii vs placebo or no intervention S. boulardii was reported to be efficacious at a daily dose <300 mg/d (5 RCTs, n = 873, mean difference (MD) −0.84 d; high heterogeneity I2 = 91%; or 500 mg/d (15 RCTs, n = 2248, MD −0.86 d; I2 = 58%); or >500 mg/d (1 RCT, n = 41, MD −2.76 d)   For those treated with S. boulardii compared with the control group, reduced duration of hospitalization (8 RCTs, n = 999, MD −0.85 d, 95% CI −1.35 to −0.34; I2 = 91%) was reported   On day 2 to day 7 of treatment, S. boulardii reduced the risk of diarrhea   Adverse effects were comparable between the groups
Ragavan et al./ Retrospective analysis[29] Indian children (n = 160, age: 0 to 18 years) with acute diarrhea Oral rehydration solution and zinc with or without S. boulardii CNCM I-745 (250 mg twice daily) In the S. boulardii group, the median duration of diarrhea post-treatment was significantly shorter (3 days) vs the non- S. boulardii group (4 days) In the S. boulardii group, a significant reduction in the frequency of stools was observed post-treatment (1.7 vs 2.5 in the non- S. boulardii group).
McFarland et al./ A systematic review (22 RCTs) and meta-analysis (17 RCTs)[30] Treatment for Indian PAGE patients (n = 4059) Five single-strain probiotics and 3 multi-strained mixtures (Strains studied include S. boulardii CNCM I-745, L. rhamnosus GG, B. clausii O/C, SIN, N/R, T, Bifilac (4 strains), B. clausii UBBC-07, L. casei DN114001, L. sporogenes, and 8 strain mixture S. boulardii CNCM I-745 had the strongest effect on shortening the duration of diarrhea (standardized mean difference, –1.86 d; 95% CI, –2.8 to –0.9), S. boulardii and L. rhamnosus GG significantly reduced hospital stays (−1.8 and −1.1 d, respectively), while B. clausii had no effect S. boulardii significantly reduced the frequency of stools/day by day 4, and L. rhamnosus GG was reduced by day 5
Fu et al./ Systemic review and meta-analysis (10 studies)[31] Children with acute gastroenteritis (n = 1282, aged <5 years) S. boulardii vs control S. boulardii could effectively shorten diarrhea duration (MD = 19.70, 95% CI, -24.87, 14.52) and reduce the length of hospital stay (MD = −0.91, 95% CI: -1.28, -0.54) A significantly lower relative risk of continued diarrhea was observed in the treatment group after 1-day treatment (RR = −0.31, 95% CI, 0.59, 0.03) and 3 days of treatment (RR = 0.52, 95% CI: 0.41, 0.66) vs the control group After 3 days of treatment, S. boulardii reduced the average number of diarrhea by about 1.03 (MD= −1:03, 95% CI: -1.53, -0.53) No adverse drug reactions were reported in either group
S. boulardii vs other probiotics for management of AAD and PAGE
McFarland et al./ meta-analysis[32] Children on antibiotics Sixteen different types of probiotics were combined S. boulardii and L. rhamnosus displayed significant efficacy for pediatric AAD when pooled (pooled RR 0.43, 95% CI 0.21-0.86).
Vineeth et al.[33] Indian children suffering from rotaviral diarrhea (n = 80) The average dose of S. boulardii (500 mg/day) vs B. clausii (10 mL/day) In the S. boulardii group, the total mean duration of diarrhea was significantly shorter vs the B. clausii group
Blaabjerg et al./ Systematic review and meta-analysis, 17 RCTs[34] Outpatients of all ages on antibiotics (n = 3631) Lactobacilli spp., Lactococcus spp., Streptococcus spp. Bifidobacterium spp., Saccharomyces spp., Leuconostoc cremoris, Bacillus spp., Clostridium spp., or alone or in combination In a subgroup analysis, S. boulardii (four studies) showed a significantly lower risk of AAD vs control (RR 0.41; 95% CI 0.30 to 0.57), while this was not observed in the combination of L. acidophilus La-5 and B. lactis Bb-12 (2 studies) (RR 0.79; 95% CI 0.47 to 1.33)
Vidjeadevan et al./ RCT[35] Children (n = 105, aged 6-36 months) with acute diarrhea Group A received ORS and zinc; Group B received ORS, zinc and S. boulardii; Group C received ORS, zinc, and B. clausii The mean duration of diarrhea was 108 hours for group A, while 72 hours and 96 hours for group B and group C, respectively. The mean duration of diarrhea was highest in group A (108 hours) and lowest in group B (72 hours)
Johnston et al./ Cochrane review, 33 studies[36] Children receiving antibiotics (0 to 18 years, n = 6352 participants) Probiotics assessed included Bacillus spp., Bifidobacterium spp., Clostridium butyricum, Lactobacilli spp., Lactococcus spp., Leuconostoc cremoris, Saccharomyces spp., or Streptococcus spp., alone or in combination, placebo or no treatment Among various probiotics, placebo or no treatment, L. rhamnosus or S. boulardii at 5 to 40 billion colony forming units/day were the most appropriate probiotics for the prevention of AAD
Li et al./ Bayesian network Meta-analysis (21 interventions)[37] Children with acute diarrhea (n = 13,443) Probiotic interventions could be divided into single-strain and multi-strain probiotics. The single-strain probiotics included S. boulardii, L. rhamnosus GG, L. reuteri, B. clausii, L. acidophilus, B. lactis, L. sporogenes, L. plantarum, E. coli Nissle 1917 (ECN 1917), L. paracasei, and E. faecium. Multiple-strain probiotics included L. species (spp.), L. spp. + B. spp., L. spp. + B. spp.+ S. spp., L. spp. + S. spp., B. spp. + S. spp., Bacillus spp. + E. spp. + Clostridium spp., L. spp. + B. spp. + E. spp., L. spp. + B. spp. + Pediococcus spp., and L. spp. + S. spp. + C. spp. + Bacillus spp. Control arm: Placebo/no treatment S. boulardii among all the probiotics was the most effective in reducing both duration of diarrhea (vs placebo) and the risk of diarrhea lasting ≥2 days (vs placebo or no treatment). It [Odds ratio (OR) = 0.22; 95%CI, 0.11, 0.41] significantly decreased the risk of diarrhea lasting ≥2 days versus placebo or no treatment
Altcheh et al./A two-arm parallel, randomized trial[38] Children (n = 317, 6 months to 5 years old) with mild-moderate acute diarrhea Randomized to 5 days of either S. boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B. clausii (n = 158). Post-probiotic treatment follow-up was done for 7 days S. boulardii CNCM I-745 displayed a significant decrease (P = 0.04) in the mean duration of diarrhea (64.6 hours, 95% CI 56.5-72.8) in comparison with B. clausii (78.0 hours, 95% CI 69.9-86.1) Both treatments were well tolerated
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Safety of S. boulardii

A recent study reports that the probiotic E. coli strain Nissle 1917 produces in vitro and in vivo colibactin and subsequently induces mutagenic DNA damage. This is a serious safety concern that should not be ignored keeping in mind the health of patients and the general public overall [39]. As the genotoxic activity of this strain cannot be dissociated from its probiotic activity, the safety aspects of large-scale use of this probiotic strain need to be reassessed. This brings up an important issue of side effects that may be associated with any effective probiotic [40].

S. boulardii CNCM I-745 is considered to be a safe probiotic. Clinical trials have not reported any side effects with S. boulardii [19]. Very rarely, in critically ill and/or immunocompromised patients, increased amounts of S. cerevisiae infections (fungemia) have been observed [41]. For immunocompromised patients, even opening a packet of S. boulardii can lead to air contamination, increasing the risk of infection [42]. However, meta-analysis has reported S. boulardii to be safe in children suffering from acute diarrhea [43].

Global recommendations for S. boulardii as a Probiotic

Table 4 provides the global recommendations for S. boulardii as a probiotic.

Table 4. Global recommendations for S. boulardii as a probiotic.

Abbreviations- IAP: Indian Academy of Paediatrics; ESPGHAN: European Society for Paediatric Gastroenterology; Hepatology, and Nutrition AAD: Antibiotic-associated diarrhea; AGE: Acute gastroenteritis; HP: Helicobacter pylori.

Sr. No. Recommended Strain Recommending agency Year of recommendation Recommended indication (dose) Not recommended Quality of evidence
1 S. boulardii IAP[44] 2022 Adjuvant therapy in acute diarrhea (250-750 mg/day)   Very low-to-low
2   S. boulardii ESPGHAN [45] 2022 Acute gastroenteritis in children (250–750 mg/day)   - Low
Prevention of AAD (≥5 billion CFU per day) - Moderate
S. boulardii ESPGHAN[46] 2020 Acute gastroenteritis in children as an adjunct treatment to oral rehydration therapy (250-750 mg/day)   Low
Bacillus clausii - NOT recommended for the prevention of AAD Very low
3 S. boulardii ESPGHAN[47] 2016 Preventing AAD in children   Moderate
Prevention of C. difficile-associated diarrhea in children Low
4 S. boulardii CNCM I-745 World Gastroenterology Organization[48] 2017 AAD in adults (5x109 CFU/capsule or 250 mg twice daily)   Level 1
Prevention of C. difficile–associated diarrhea (or prevention of recurrence) in adults (5x109 CFU/capsule or 250 mg twice daily) Level 3
Co-adjuvant therapy for HP eradication (5x109 CFU/capsule or 250 mg twice daily) Level 1
Prevention of AAD (250–500 mg) Level 1
5 S. boulardii  CNCM I-745 Latin-American Experts[49] 2015 Acute infectious diarrhea   Grade of evidence:1a
Prevention of AAD, prevention of traveler’s diarrhea   Grade of evidence:1b
6 S. boulardii European Paediatric Association Expert Panel[50] 2018 Prevention of AAD, acute gastroenteritis (adjunct to the oral rehydration therapy) (250-750 mg), Prevent C. difficile-associated diarrhea   -
7 S. boulardii World Journal of Gastroenterology-2017 Asia Pacific (APAC) region[51] 2017 For AGE, in adjunct to oral rehydration therapy   Strong
AAD Strong
C. difficile-associated diarrhea Low
8 S. boulardii ESPGHAN [45] 2023 AAD   Moderate
Acute gastroenteritis   Low
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Conclusions

Probiotic S. boulardii CNCM I-745, by its unique properties, acts in a variety of ways to exert its pathogen-binding, immunological, and anti-toxin actions. Additionally, it cannot transfer genetic material, making it a potential candidate as a probiotic for preventing antibiotic resistance. S. boulardii stands out among the other probiotics as one of the most effective for avoiding AAD in children. In comparison to L. rhamnosus GG and a few strains of B. clausii, S. boulardii CNCM I-745 shows a significantly reduced mean duration of diarrhea in PAGE patients. Furthermore, because of its proven efficacy and safety, it is recommended by ESPGHAN and other global bodies for the prevention and treatment of acute diarrhea. Thus, S. boulardii CNCM I-745 is one of the preferred choices of probiotics for the management of AAD and PAGE due to its distinct advantages over bacterial probiotics as well as its favorable efficacy and safety profile.

Acknowledgments

We would like to acknowledge Scientimed Solutions Pvt. Ltd., Mumbai for assistance in developing the manuscript.

The authors have declared financial relationships, which are detailed in the next section.

Neha, Devesh Kumar Joshi, Krishna Chaitanya Veligandla, Rahul Rathod, and Bhavesh Kotak declare(s) employment from Dr. Reddy’s Laboratories Ltd. The authors Neha and Devesh Kumar Joshi are serving as the Medical Advisor at Dr. Reddy’s Laboratories Ltd. Hyderabad. Similarly, the authors Krishna Chaitanya Veligandla, Rahul Rathod, and Bhavesh Kotak are also working as Medical Cluster Head, Head Ideation & Clinical Research, and Head Medical Affairs, respectively, at Medical Affairs Department, Dr. Reddy’s Laboratories Ltd. Hyderabad, India.

Funding Statement

The article processing charge (APC) was funded by Dr. Reddy’s Laboratories Ltd.

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