Probiotics for the Management of Infectious Diseases: Reviewing the State of the Art

Abstract

This review aims to provide insight into the potential of probiotics as a clinical modality targeted at infectious diseases by creating a comprehensive overview of the state of the art of research and development efforts as shown by patents and clinical trials of the past 20 years. Data were retrieved from patent and clinical trial databases to reflect the long- and short-term developments of probiotics research. The data were analyzed to extract information on the total number of patents and trials for each indication, application date and location, and applicant/sponsor type. A total of 80 infectious diseases were investigated, precipitating in 789 patents and 602 clinical trials for 67 indications studied as targets of probiotics. An increasing trend was seen for the number of patents and clinical trials that were applied for since 1999 with the highest number of patents and clinical trials targeted to digestive tract, respiratory, and urogenital indications. Overall, research demonstrated a substantial interest in probiotics targeting infectious diseases, which was in line with reported unmet needs and global probiotics sales estimates. However, the declining rate of translation from patents to clinical trials indicates that there are some barriers obstructing the research process.

Keywords: clinical trials; infectious diseases; patents; probiotics; state of the art.

Figure 1

A total of 789 patents and 602 clinical trials were included for analysis. (A) Patents. n = number of results retrieved from Espacenet. (B) Clinical trials. n = number of results retrieved from ClinicalTrials.gov (CT.gov), ClinicalTrialsRegister.eu (CTR.eu), and the International Clinical Trials Registry Platform (ICTRP).

Figure 2

Focal points of patents and clinical trials were digestive tract, urogenital, and respiratory symptoms. Percentages of patent and clinical trial results for each category of infectious diseases based on clinical manifestation. The 20 infectious diseases that were mentioned most frequently in patents are displayed in the insert graph (see Supplementary Figure 1 for complete graph).

Figure 3

Patents and clinical trials showed an increasing trend since the year 2000. (A) CT/P = clinical trials/patents. Displayed are the cumulative number of patents and clinical trials as well as the ratio of clinical trials and patents. (B) Cumulative number of patents for each group of clinical symptoms of infectious diseases. (C) Cumulative number of clinical trials for each group of clinical symptoms of infectious diseases. Cardiovascular and central nervous system symptoms are obscured due to overlap with hemorrhagic fevers. The years 2020 and 2021 may not be complete due to the 18-month patent application period and COVID-19-related disruptions.

Figure 4

China, the United States, South Korea, and Iran were the most frequently reported locations of patent applications and clinical trials. (A) Number of patent applications per country or organization. Total exceeds n = 789 due to most patents being applied for in multiple countries. (B) Number of clinical trials per country. Numbers not shown on the map are included in the bar graph.

Figure 5

Main applicant/sponsor types included industry and academia. Values represent percentages of the number of included patents and clinical trials, respectively.