Kampo Research Articles

Seed set by artificial pollination and seed storage under cryogenic, freezer and dry conditions in the medicinal plant Uncaria rhynchophylla

Abstract Uncaria rhynchophylla (Rubiaceae), a woody liana with significant medicinal value, has been used as a traditional Japanese and Chinese medicine. While effective seed production is required for breeding and efficient seedling production, the physiology of sexual reproduction remains largely unknown in this species. Therefore, we first observed the flowering behaviour, and next attempted artificial pollination using flowering individuals in a greenhouse. In this study it became clear that this species sets seeds by allogamy, but not by autogamy. The obtained seeds showed about a 90% germination rate. We also examined seed desiccation tolerance and storage conditions which are important to preserve the genetic resources. Seeds of this species were found to have a characteristic of the orthodox type, having high desiccation tolerance. Seeds after 6 months of storage at + 22, −20 and −160°C showed comparable germination rates to the seeds before storage.

Role of visual information in multimodal large language model performance: an evaluation using the Japanese nuclear medicine board examination.

This study aimed to assess the performance of state-of-the-art multimodal large language models (LLMs), specifically GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro, on Japanese Nuclear Medicine Board Examination (JNMBE) questions and to evaluate the influence of visual information on the decision-making process. This study utilized 92 questions with images from the JNMBE (2019-2023). The LLMs' responses were assessed under two conditions: providing both text and images and providing only text. Each model answered all questions thrice, and the most frequent answer choice was considered the final answer. The accuracy and agreement rates among the model answers were evaluated using statistical tests. GPT-4o, Claude 3 Opus, and Gemini 1.5 Pro exhibited no significant differences in terms of accuracy between the text-and-image and text-only conditions. GPT-4o and Claude 3 Opus demonstrated accuracies of 54.3% (95% CI: 44.2%-64.1%) each when provided with both text and images; however, they selected the same options as in the text-only condition for 71.7% of the questions. Gemini 1.5 Pro performed significantly worse than GPT-4o under text and image conditions. The agreement rates among the model answers ranged from weak to moderate. The influence of images on decision-making in nuclear medicine is limited to the latest multimodal LLMs, and their diagnostic ability in this highly specialized field remains insufficient. Improving the utilization of image information and enhancing the answer reproducibility are crucial for the effective application of LLMs in nuclear medicine education and practice. Further advancements in these areas are necessary to harness the potential of LLMs as assistants in nuclear medicine diagnosis.

Preventive and therapeutic effects of ephedrine alkaloids-free Ephedra Herb extract on paclitaxel-induced neuropathic pain.

Currently, there are no effective prophylactic or therapeutic drugs for the treatment of paclitaxel (PTX)-induced peripheral neuropathic pain (PTX-PNP), highlighting the urgent need for the development of effective prophylactic and therapeutic drugs. In this study, we initially compared the efficacy of Ephedra Herb extract (EHE) with that of ephedrine alkaloids-free Ephedra Herb extract (EFE), which lacked ephedrine alkaloids (EAs)-associated side effects, against the onset of PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia in mice. EHE and EFE demonstrated comparable preventive effects on the PTX-PNP in a dose-dependent manner. These results indicated that the preventive properties of EHE were independent of the EAs. Since elderly people are overwhelmingly more susceptible to developing cancer, we considered that EFE has greater benefits than EHE, so we conducted a study focused on the effects of EFE. EFE showed dose-dependent preventive effects on the onset of PTX-PNP. As a result of detailed investigation, coadministration of PTX and EFE (Co-EFE) was more effective than preadministration of EFE alone (Pre-EFE). And the effects of Co-EFE was same with the effect of preadministrationof EFE and then coadministration of PTX and EFE (P&C-EFE). Additionally, Co-EFE after the onset of PTX-PNP improved PTX-induced mechanical allodynia, thermal hyperalgesia, and cold allodynia, confirming the therapeutic efficacy of EFE on PTX-PNP. In contrast, goshajinkigan, a Kampo medicine, and diclofenac, a non-steroidal anti-inflammatory drug, showed minimal therapeutic effects on PTX-PNP. These findings demonstrate the significant potential of EFE as a novel, safe prophylactic and therapeutic agent against PTX-PNP.

Machine learning model for predicting the cold-heat pattern in Kampo medicine: a multicenter prospective observational study.

The purpose of this study was to predict the four cold-heat patterns in patients who have the subjective symptoms of the cold-heat pattern described in the International Classification of Diseases Traditional Medicine Conditions - Module 1 by applying a machine learning algorithm. Subjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern. We included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold-heat pattern. We developed a prediction model on cold-heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold-heat pattern diagnosis by the physician.

Daikenchuto, a Japanese herbal medicine, ameliorates experimental colitis in a murine model by inducing secretory leukocyte protease inhibitor and modulating the gut microbiota.

Inflammatory bowel disease (IBD) is a refractory inflammatory disorder of the intestine, which is probably triggered by dysfunction of the intestinal epithelial barrier. Secretory leukocyte protease inhibitor (SLPI) secreted by colon epithelial cells protects against intestinal inflammation by exerting anti-protease and anti-microbial activities. Daikenchuto (DKT) is one of the most commonly prescribed Japanese traditional herbal medicines for various digestive diseases. Although several animal studies have revealed that DKT exerts anti-inflammatory effects, its detailed molecular mechanism is unclear. This study aimed to clarify the anti-inflammatory mechanism of DKT using a murine colitis model, and to evaluate its potential as a therapeutic agent for IBD. Experimental colitis was induced in wild-type (WT) mice and SLPI-deficient (KO) mice by dextran sulfate sodium (DSS) after oral administration of DKT. The resultant clinical symptoms, histological changes, and pro-inflammatory cytokine levels in the colon were assessed. Expression of SLPI in the colon was detected by Western blotting and immunohistochemistry. Composition of the gut microbiota was analyzed by 16S rRNA metagenome sequencing and intestinal metabolites were measured by gas chromatography-mass spectrometry analysis. Intestinal epithelial barrier function was assessed by oral administration of FITC-dextran and immunostaining of tight junction proteins (TJPs). Oral administration of DKT increased the number of butyrate-producing bacteria, such as Parabacteroides, Allobaculum, and Akkermansia, enhanced the levels of short-chain fatty acids, including butyrate, in the colon, induced SLPI expression, and ameliorated DSS-induced colitis in WT mice. We found that mouse colon carcinoma cell line treatment with either DKT or butyrate significantly enhanced the expression of SLPI. Moreover, supplementation of DKT protected the intestinal epithelial barrier with augmented expression of TJPs in WT mice, but not in KO mice. Finally, the composition of the gut microbiota was changed by DKT in WT mice, but not in KO mice, suggesting that DKT alters the colonic bacterial community in an SLPI-dependent manner. These results indicate that DKT exerts anti-inflammatory effects on the intestinal epithelial barrier by SLPI induction, due, at least in part, to increased butyrate-producing bacteria and enhanced butyrate levels in the colon. These results provide insight into the mechanism of the therapeutic effects of DKT on IBD.

Physician Kitasato Shibasaburō: Achievements and posthumous veneration in Shintō

In 2024, the medical community celebrates an important date – 130 years since the discovery of the causative agent of plague, which was independently isolated by the Japanese physician Kitasato Shibasaburō (1853–1931) and the French physician Alexandre Yersin (1863–1943). Although the former had done so a few days earlier, as a result of misunderstanding and forgery, the honor of the discovery was given to A. Yersin, and the genus to which the bacterium is assigned is named in his honor. As it happened, Kitasato is almost unknown in European science, and some of his achievements are attributed to other researchers. In this article, for the first time in the Russian-language scientific literature, his life and achievements are discussed in detail. The outstanding physician isolated a pure culture of Clostridium tetani, was the first in the world to propose serum therapy, isolated Yersinia pestis, educated a galaxy of outstanding physicians and was one of the founders of modern Japanese public health (state sanitary and epidemiological supervision), preventing the establishment of plague in the Japanese islands. His services to Japanese and world medicine are truly immense. No less interesting is his posthumous veneration in Shinto, which was combined with the veneration of the German physician Robert Koch (1843–1910), a teacher and senior friend of Kitasato Shibasaburō. The deification of scientists is an extraordinary practice and represents a significant cultural phenomenon. It should be noted, however, that the cult of Koch-Kitasato is local and actually confined to the Kitasato Institute, where scholars are honored as patrons of the Institute. Interestingly, the other discoverer of the plague microbe, Alexandre Yersin, is deified within Vietnamese Mahayana Buddhism and as a god-patron (thành hoàng) within Vietnamese folk religion, which paradoxically unites the posthumous fate of these scientists.

Pathway-based prediction of the therapeutic effects and mode of action of custom-made multiherbal medicines.

Multiherbal medicines are traditionally used as personalized medicines with custom combinations of crude drugs; however, the mechanisms of multiherbal medicines are unclear. In this study, we developed a novel pathway-based method to predict therapeutic effects and the mode of action of custom-made multiherbal medicines using machine learning. This method considers disease-related pathways as therapeutic targets and evaluates the comprehensive influence of constituent compounds on their potential target proteins in the disease-related pathways. Our proposed method enabled us to comprehensively predict new indications of 194 Kampo medicines for 87 diseases. Using Kampo-induced transcriptomic data, we demonstrated that Kampo constituent compounds stimulated the disease-related proteins and a customized Kampo formula enhanced the efficacy compared with an existing Kampo formula. The proposed method will be useful for discovering effective Kampo medicines and optimizing custom-made multiherbal medicines in practice.

Effects of morroniside isolated from Cornus officinalis fruits on functional gastrointestinal disorders and gastric ulcer in mice

The dried fruits of Cornus officinalis (Cornaceae) are used in Kampo medicine (e.g. Hachimigan and Goshajinkigan) to treat senile osteoporosis, diabetes, gastric atony, frequent urination, and diarrhea/constipation associated with aging. The present study investigated the effects of a C. officinalis fruit extract and morroniside, an iridoid compound from isolated these fruits, on the reduction in gastric emptying small intestinal motility caused by 5-hydroxytryptamine (5-HT) and 1-(3-chlorophenyl) biguanide (5-HT3 receptor agonist), and gastric ulcers induced by 150 or 75 mM HCl/90 % EtOH (HCl-EtOH) and/or 5-HT in mice. C. officinalis extract (500 mg/kg) and morroniside (20 and 50 mg/kg) suppressed the reduction in gastric emptying induced by 5-HT- and 5-HT3 agonist. C. officinalis extract, morroniside and 5-HT3 receptor antagonist (ramosetron) attenuated 5-HT-induced diarrhea. Furthermore, morroniside (20 and 50 mg/kg) prevented EtOH/HCl-induced gastric ulcers and those caused by 5-HT. Morroniside (20 and 50 mg/kg) attenuated elevations in the plasma levels of corticosterone, corticotropin-releasing factor (CRF), and adrenocorticotropic hormone (ACTH) in 75 mM HCl/90 % EtOH- and 5-HT-treated mice. The results obtained herein suggest the potential of morroniside as an effective treatment for irritable bowel syndrome, such as diarrhea and functional dyspepsia (reductions in gastric emptying and small intestinal motility), caused by 5-HT. The present study suggests a role for morroniside in the regulation of elevations in CRF, ACTH, and corticosterone levels through hypothalamic-pituitary-adrenal axis activity induced by stress loading, such as a 5-HT treatment and/or HCl/EtOH stimulation.

Analgesic effect of Keishinieppiittokajutsubu on low barometric pressure-induced pain response in arthritic model rats

Rheumatoid arthritis (RA) is a disease that causes inflammation of joints, resulting in pain and swelling. Reduced barometric pressure induces painful symptom of RA, but there is no appropriate animal model and pharmacological evaluation. Keishinieppiittokajutsubu (KNEIJB), a Kampo medicine used to treat RA; however, its mechanism of action is not clear. Here, we found that KNEIJB suppressed the low barometric pressure (LP)-induced pain response in CFA-induced arthritic model rats. Furthermore, we found that KNEIJB reduced plasma IL-6 levels. These results suggest that KNEIJB might be beneficial in the treatment of RA or some other arthralgia induced by LP.

The Use of Japanese Traditional (Kampo) Medicines Before and During Pregnancy in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Japanese traditional (Kampo) medicines are often used for pregnant women in Japan. However, no comprehensive studies have been conducted regarding the self-reported use of these medicines during pregnancy. This study investigated the use of Kampo medicines during pregnancy in Japan using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). Questionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (July 2013 to March 2017) at approximately 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed Kampo medicines use over three periods: (1) 12 months before pregnancy diagnosis, (2) the period between pregnancy diagnosis and around Week 12 of pregnancy and (3) from around Week 12 of pregnancy. In total, 19 220 women were included in the analysis. The proportions using prescribed Kampo medicines were 4.1% before pregnancy diagnosis, 4.5% from diagnosis to Week 12% and 4.5% after Week 12 of pregnancy. The most frequently prescribed Kampo medicines were tokishakuyakusan (1.0%) before pregnancy diagnosis, shoseiryuto (1.3%) from diagnosis to Week 12 and shoseiryuto (1.5%) Post-week 12. Sixty of the pregnant women used Kampo medicines containing crude drugs, which should be administered cautiously during pregnancy. The proportion of Kampo medicines use before and during pregnancy was 4%-5%. Some pregnant women used Kampo medicines containing crude drugs that should be administered cautiously during pregnancy. Further research is required to determine the safety of Kampo medicines during pregnancy.

Colon protective effect of Japanese Kampo medicine Daikenchuto by modulating gut microbiota and inducing SLPI

Colon protective effect of Japanese Kampo medicine Daikenchuto by modulating gut microbiota and inducing SLPI

Traditional clinical symptoms and signs: Kampo pattern diagnosis in modern gastrointestinal disease.

In traditional Japanese Kampo medicine, a profound anamnesis is completed by clinical examination. The resulting clinical image forms the basis of the patient's diagnosis pattern, including the recent mental, physical, and social contexts. Kampo questionnaires support pattern diagnosis and bridge traditional and Western medicine diagnoses. Traditional Kampo therapy is tailored to a specific body constitution, while Western medicine treatment is tailored to a specific disease. The aims of this study were to analyze whether traditional Kampo diagnosis is applicable to German patients and whether specific symptom patterns are characteristic for defined diseases. This study validates for the first time a Kampo questionnaire adapted for German patients. The analysis focuses on patients with gastrointestinal diseases, the main field for Kampo medicines. In total, we prospectively included 251 participants; of those, 58 were cancer patients (23.1%), 35 had Crohn's disease (13.9%), 18 had ulcerative colitis (7.2%), 17 had irritable bowel syndrome (6.8%), and 103 had other abdominal diseases (41%), as well as 20 German controls (8%). The patient population consisted of 144 female (57.4%) and 107 male (42.6%) participants. The median age was 65years. The disease duration (average: 211months) varied from 1month (cancer patient) to 540months (patient with Crohn's disease). The scores for questions on the state of mind were significantly higher in patients with inflammatory bowel disease (IBD) as well as irritable bowel syndrome (IBS)-in comparison to the tumor and control groups. This was reflected in questions about abdominal discomfort, appetite, fecal habits, and cold sensation. Accordingly, symptoms of Qi (i.e., vital energy) deficiency were mostly observed in patients with chronic diseases such as Crohn's disease and ulcerative colitis. Defined symptom combinations did not reflect conventional Western diagnosis. Our study results show that symptom patterns are independent of the underlying disease. They rather depict the individual patient within an individual time frame. Traditional Kampo questionnaires were found to be valid for the analysis of a patients' body constitution (sho) and serve as a guide for Kampo treatment. We propose that individual pattern diagnosis should be taken into account to help treatment individualization.

3-epi-18β-Glycyrrhetinic Acid or Its Glucuronide, the Metabolites of Glycyrrhizinic Acid with Individual Differences, Correlated with Diagnostic Marker for Licorice-Induced Pseudoaldosteronism in Humans.

Licorice is a crude drug that is used in traditional Japanese Kampo medicine and is also used as a sweetener. Occasionally, it causes pseudoaldosteronism (PsA) as a side effect. The major symptoms include hypokalemia, hypertension, edema, and low plasma aldosterone levels. PsA might be caused by the metabolites of glycyrrhizinic acid (GL), a component of licorice. The development of PsA markedly varies among individuals; however, the factors that cause these individual differences remain unknown. In this study, 78 patients who consumed Kampo medicines containing licorice were enrolled, and their laboratory data, including serum potassium levels, plasma aldosterone concentrations (PAC), and the concentrations of GL metabolites in the residual blood and/or urine samples were evaluated. Of the 78 participants, 18β-glycyrrhetinic acid (GA), 3-epi-GA, 3-oxo-GA, 18β-glycyrrhetinyl-30-O-glucuronide (GA30G), and 3-epi-GA30G were detected in the serum samples of 65, 47, 63, 62, and three participants, respectively. Of the 29 urine samples collected, GA30G and 3-epi-GA30G were detected in 27 and 19 samples. 3-epi-GA30G is a newly found GL metabolite. Moreover, 3-epi-GA, 3-oxo-GA, and 3-epi-GA30G were identified in human samples for the first time. High individual differences were found in the appearances of 3-epi-GA in serum and 3-epi-GA30G in urine, and the concentrations of these metabolites were correlated with serum PsA markers. The inhibitory titers of 3-epi-GA, 3-oxo-GA, GA30G, and 3-epi-GA30G on human 11β-hydroxysteroid dehydrogenase type 2 were almost similar. These findings suggest that 3-epi-GA and/or 3-epi-GA30G are associated with individual differences in the development of PsA. SIGNIFICANCE STATEMENT: In this study, we detected 3-epi-18β-glycyrrhetinic acid (3-epi-GA) in human serum for the first time. We also identified 3-epi-18β-glycyrrhetinyl-30-O-glucuronide (3-epi-GA30G) as a novel glycyrrhizinic acid (GL) metabolite in human urine. These GL metabolite levels showed correlations with markers of PsA. Additionally, there are individual differences in whether they appear in the serum/urine. In conclusion, 3-epi-GA/3-epi-GA30G correlates with individual differences in the development of PsA.

The Effect of Nonpharmacological Methods on Preoperative Anxiety in Breast Surgery Patients: Meta-analysis

PurposeTo investigate the effect of nonpharmacological methods on anxiety before breast surgery, using the meta-analysis method. DesignA meta-analysis. MethodsNine electronic databases were searched to identify studies published up to October 2023. The study was carried out in accordance with Preferred Reporting Items for Systematic Review and Meta-analyses 2020 and Cochrane 2021 recommendations. The Risk of Bias 2 tool was used to assess the risk of bias. Heterogeneity and publication bias were also assessed. FindingsA search of 9 electronic databases identified 280 records. Six studies that met the inclusion criteria were eligible for meta-analysis. All the trials explained how the randomization was done. The studies selected were published between 2016 and 2022. A total of 519 female patients were included in the selected trials, 303 in the intervention group and 216 in the control group. The studies included aromatherapy, music, electro-acupuncture, and Yokukansan Kampo medicine practices. A meta-analysis was performed with anxiety levels measured immediately before surgery. In addition, a subgroup analysis was performed with trials that used anxiety-specific scales before surgery and trials that used aromatherapy. ConclusionsThe results of this meta-analysis indicated a moderate efficacy of nonpharmacological approaches, whereas aromatherapy showed a relatively lower efficacy in reducing preoperative anxiety in breast surgery patients.

Persistent cough in mild COVID‐19 successfully treated with chikujountanto, a traditional Kampo medicine: An observational cohort study

Persistent cough in mild <scp>COVID</scp>‐19 successfully treated with <scp><i>chikujountanto</i></scp>, a traditional Kampo medicine: An observational cohort study

Chronic pantalgia due to nociplastic pain managed with traditional Japanese medicine: A case report

Chronic pantalgia due to nociplastic pain managed with traditional Japanese medicine: A case report

Investigation of Japanese traditional medicines, Kampo, for the treatment of preeclampsia

Investigation of Japanese traditional medicines, Kampo, for the treatment of preeclampsia

Association between complementary use of Goreisan (a Japanese herbal Kampo medicine) and heart failure readmission: A nationwide propensity score-matched study

BackgroundGoreisan, a Japanese herbal medicine, possesses aquaretic properties to regulate body fluid homeostasis and may therefore be effective as a complement to standard therapy in improving outcomes in patients with heart failure (HF). MethodsWe retrospectively identified 431,393 patients (mean age 79.2 ± 12.6 years; male 52.3 %) who were admitted for HF for the first time and were discharged alive with standard HF medications between April 2016 and March 2022, using the Japanese Diagnosis Procedure Combination database. We divided patients into two groups according to the prescription of Goreisan at discharge: patients who received standard HF medications plus Goreisan and those who received standard medications alone. We compared the incidence of HF readmission within 1 year after discharge between the groups using propensity score matching. ResultsOverall, Goreisan was prescribed in 1957 (0.45 %) patients at discharge. Patients who received Goreisan were older and received diuretics more frequently than those who did not. One-to-four propensity score matching created a cohort of 1957 and 7828 patients treated with and without Goreisan, respectively. No significant difference was found in the incidence of 1-year HF readmission between the groups [22.1 % vs. 21.7 %; hazard ratio (HR) = 1.02, 95 % confidence interval (CI) = 0.92–1.13]. This result was consistent with that from competing risk analysis (subdistribution HR = 1.02, 95 % CI = 0.92–1.13) and across clinically relevant subgroups except for renal disease. Goreisan use was associated with a lower incidence of HF readmission among patients with renal disease (HR = 0.77, 95 % CI = 0.60–0.97), but not among those without (HR = 1.09, 95 % CI = 0.97–1.23; p for interaction = 0.009). ConclusionsThis nationwide propensity score-matched analysis did not demonstrate that complementary Goreisan use at discharge was associated with a lower incidence of 1-year HF readmission in patients with HF receiving standard medications. An ongoing randomized trial is awaited to establish the effectiveness of Goreisan use in patients with HF.

Shibasaburo Kitasato (1853-1931): Pioneer of Japanese Medicine and Global Immunology Innovator.

Shibasaburo Kitasato (1853-1931), a pivotal figure in modern Japanese medicine, made groundbreaking contributions to bacteriology and immunology. His achievements include pure cultivation of the tetanus bacillus and the development of serum therapy, which continue to influence modern immunology and vaccination strategies. Kitasato established the Institute for Infectious Diseases in Japan, the Kitasato Institute, played a crucial role in establishing the Keio University School of Medicine, and served as the first president of the Japan Medical Association. His international collaboration with Robert Koch and Emil von Behring elevated Japan's status in global medical research. Kitasato's research philosophy emphasizes clinical applicability and passionate pursuit of effective topics, inspiring the generation of prominent Japanese medical researchers. This study highlights Kitasato's life, work, and enduring impact on medical research, education, and healthcare administration. Kitasato's legacy, commemorated on the new 1000-yen banknote in 2024, continues to serve as an inspiration for contemporary medical professionals worldwide.

Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023.

The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and antidiarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogues, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.