The Relationship Between Gut Microbiome Estrobolome and Breast Cancer: A Systematic Review of Current Evidences.

Breast cancer is the most frequent kind of cancer and the second leading cause of mortality worldwide, behind heart disease. Next-generation sequencing technologies enables for unprecedented enumeration of human resident gut microorganisms, conferring novel insights into the role of the microbiota in health and individuals with breast cancer. A growing body of research on microbial dysbiosis seems to indicate an elevated risk of health complications including cancer. Although several dysbiosis indices have been proposed, their underlying methodology, as well as the cohorts and conditions of breast cancer patients are significantly different. To date, these indices have not yet been thoroughly reviewed especially when it comes to researching the estrogen-gut microbiota axis. Instead of providing a thorough rating of the most effective diversity measurements, the current work aims to be used to assess the relevance of each study's findings across the demographic data, different subtypes, and stages of breast cancer, and tie them to the estrobolome, which controls the amount of oestrogen that circulates through humans. This review will cover 11 studies which will go into a detailed discussion for the microbiome results of the mentioned studies, leaving to the user the final choice of the most suited indices as well as highlight the observed bacteria found to be related to the estrobolome in hopes of giving the reader a better understanding for the biological cross-talk between gut microbiome and breast cancer progression. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01135-z.

The impact of diet and ethnicity on gut microbiota variation in irritable bowel syndrome: A multi-center study.

BACKGROUND AND AIM: The gut microbiota in irritable bowel syndrome (IBS) is known to vary with diet. We aim to (i) analyze the gut microbiota composition of IBS patients from a multi-ethnic population and (ii) explore the impact of a low FODMAP diet on gastrointestinal symptoms and gut microbiota composition among IBS patients. METHODS: A multi-center study of multi-ethnic Asian patients with IBS was conducted in two phases: (i) an initial cross-sectional gut microbiota composition study of IBS patients and healthy controls, followed by (ii) a single-arm 6-week dietary interventional study of the IBS patients alone, exploring clinical and gut microbiota changes. RESULTS: A total of 34 adult IBS patients (IBS sub-types of IBS-D 44.1%, IBS-C 32.4%, and IBS-M 23.5%) and 15 healthy controls were recruited. A greater abundance of Parabacteroides species with lower levels of bacterial fermenters and short-chain fatty acids producers were found among IBS patients compared with healthy controls. Age and ethnicity were found to be associated with gut microbiota composition. Following a low FODMAP dietary intervention, symptom and quality of life improvement were observed in 24 (70.6%) IBS patients. Symptom improvement was associated with adherence to the low FODMAP diet (46.7% poor adherence vs 92.9% good adherence, P = 0.014), and gut microbiota patterns, particularly with a greater abundance of Bifidobacterium longum, Anaerotignum propionicum, and Blautia species post-intervention. CONCLUSION: Gut microbiota variation in multi-ethnic IBS patients may be related to dietary intake and may be helpful to identify patients who are likely to respond to a low FODMAP diet.

MicroRNAs in Endometriosis: Insights into Inflammation and Progesterone Resistance.

Endometriosis, a non-malignant gynecological disorder influenced by estrogen, involves the growth of endometrial tissue outside the uterus. Its development includes processes such as inflammation, progesterone resistance, angiogenesis, and cell proliferation. Epigenetic factors, particularly the dysregulation of microRNAs (miRNAs), have emerged as key factors in these mechanisms in endometriosis. This review aims to unveil the intricate molecular processes that control inflammation, progesterone resistance, and miRNA functions in endometriosis. In addition, it provides a comprehensive overview of the current understanding regarding the involvement of miRNAs in the inflammatory aspects of this condition. This synthesis encompasses research investigating the molecular underpinnings of inflammation, along with the biogenesis and roles of miRNAs in endometriosis. Furthermore, it examines human studies and functional analyses to establish the intricate connection between miRNAs, inflammation, and progesterone resistance in the context of endometriosis. The results highlight the significant impact of dysregulated miRNAs on the inflammatory pathways and hormonal imbalances characteristic of endometriosis. Consequently, miRNAs hold promise as potential non-invasive biomarkers and targeted therapeutic agents aimed at addressing inflammation and enhancing the response to progesterone treatment in individuals with endometriosis.

Predicting Prognosis and Platinum Resistance in Ovarian Cancer: Role of Immunohistochemistry Biomarkers.

Ovarian cancer is a lethal reproductive tumour affecting women worldwide. The advancement in presentation and occurrence of chemoresistance are the key factors for poor survival among ovarian cancer women. Surgical debulking was the mainstay of systemic treatment for ovarian cancer, which was followed by a successful start to platinum-based chemotherapy. However, most women develop platinum resistance and relapse within six months of receiving first-line treatment. Thus, there is a great need to identify biomarkers to predict platinum resistance before enrolment into chemotherapy, which would facilitate individualized targeted therapy for these subgroups of patients to ensure better survival and an improved quality of life and overall outcome. Harnessing the immune response through immunotherapy approaches has changed the treatment way for patients with cancer. The immune outline has emerged as a beneficial tool for recognizing predictive and prognostic biomarkers clinically. Studying the tumour microenvironment (TME) of ovarian cancer tissue may provide awareness of actionable targets for enhancing chemotherapy outcomes and quality of life. This review analyses the relevance of immunohistochemistry biomarkers as prognostic biomarkers in predicting chemotherapy resistance and improving the quality of life in ovarian cancer.

Targeted Sequencing of Cytokine-Induced PI3K-Related Genes in Ulcerative Colitis, Colorectal Cancer and Colitis-Associated Cancer.

Chronic relapsing inflammatory bowel disease is strongly linked to an increased risk of colitis-associated cancer (CAC). One of the well-known inflammatory carcinogenesis pathways, phosphatidylinositol 3-kinase (PI3K), was identified to be a crucial mechanism in long-standing ulcerative colitis (UC). The goal of this study was to identify somatic variants in the cytokine-induced PI3K-related genes in UC, colorectal cancer (CRC) and CAC. Thirty biopsies (n = 8 long-standing UC, n = 11 CRC, n = 8 paired normal colorectal mucosa and n = 3 CAC) were subjected to targeted sequencing on 13 PI3K-related genes using Illumina sequencing and the SureSelectXT Target Enrichment System. The Genome Analysis Toolkit was used to analyze variants, while ANNOVAR was employed to detect annotations. There were 5116 intronic, 355 exonic, 172 untranslated region (UTR) and 59 noncoding intronic variations detected across all samples. Apart from a very small number of frameshifts, the distribution of missense and synonymous variants was almost equal. We discovered changed levels of IL23R, IL12Rß1, IL12Rß2, TYK2, JAK2 and OSMR in more than 50% of the samples. The IL23R variant in the UTR region, rs10889677, was identified to be a possible variant that might potentially connect CAC with UC and CRC. Additional secondary structure prediction using RNAfold revealed that mutant structures were more unstable than wildtype structures. Further functional research on the potential variants is, therefore, highly recommended since it may provide insight on the relationship between inflammation and cancer risk in the cytokine-induced PI3K pathway.

Effectiveness of Sterilized Symbiotic Drink Containing Lactobacillus helveticus Comparable to Probiotic Alone in Patients with Constipation-Predominant Irritable Bowel Syndrome.

BACKGROUND: This study aimed to objectively investigate whether the addition of polydextrose to sterilized probiotic containing Lactobacillus helveticus will confer benefits to constipation-predominant irritable bowel syndrome patients. METHODS: A total of 163 patients were randomized into two groups: Group A to consume 350 mL of sterilized probiotic with 5.85 g polydextrose daily for 1 week and Group B without polydextrose. Intestinal transit time, fecal pH, fecal weight, and modified Garrigues questionnaires for pre- and post-consumption were assessed. RESULTS: Median intestinal transit time was significantly reduced from 58 (IQR 43-72) to 45 (IQR 24-59) hours and 48 (IQR 31-72) to 30 (IQR 24-49) hours for Groups A and B, respectively (p < 0.01). Fecal pH for Groups A and B was significantly reduced from 6.57 ± 0.96 to 6.13 ± 0.95 (p = 0.003) and 6.58 ± 1.0 to 5.87 ± 0.83 (p < 0.001), respectively. Fecal weight for Group A was significantly increased from 8 g ± 6.4 g to 9.8 g ± 7.6 g (p = 0.003), but it was reduced for Group B from 13.3 g ± 19.4 g to 11.2 g ± 6.6 g (p = 0.308). Constipation-related symptoms were significantly improved for both groups. CONCLUSIONS: The addition of polydextrose to sterilized probiotic containing L. helveticus did not show significant benefits to constipation-predominant irritable bowel syndrome patients. However, daily consumption of sterilized probiotic containing L. helveticus with or without polydextrose for a week alleviated constipation-related symptoms and objectively reduced both fecal pH and intestinal transit time.

The Effect of Surgical Intervention of Endometriosis to CA-125 and Pain.

Endometriosis is an inflammatory condition characterised by the presence of endometrial growth beyond the uterine cavity. It is a debilitating disease requiring multiple modalities of treatment. In considering surgery as the option of treatment, the benefits should outweigh the risk. Besides direct surgical risk, intervention may lead to a reduction of ovarian reserve, in addition to premature menopause and low fecundity. To date, there is an inconclusive evidence to support any specific parameters in monitoring disease progression following surgical intervention. Serum cancer antigen (CA)-125 is expressed by coelomic epithelium and has been extensively studied as a biomarker for endometriosis. Elevated expression of CA-125 has been shown in endometrial tissues and the marker increased indirectly from peritoneal irritation that accompanies an extensive form of endometriosis. Additionally, the visual analogue scale (VAS) scores have been used as an objective measurement for measuring pain, especially in a complex disease such as endometriosis. This review aims to consolidate a series of clinical trials that utilised CA-125 level and VAS score as tools for monitoring patients undergoing surgery for endometriosis.

A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer.

BACKGROUND: Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 1010 cfu Lactobacillus and Bifidobacteria strains for six months on clinical outcomes and inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22) in patients with colorectal cancer. METHODS: Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo (n = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 (n = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit. RESULTS: The majority of cases (~ 70%) were in Duke's C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level (P < 0.05). However, there was no significant difference in the IFN-γ in both groups. CONCLUSIONS: We have shown that probiotics containing six viable microorganisms of Lactobacillus and Bifidobacteria strains are safe to be consumed at four weeks after surgery in colorectal cancer patients and have reduced pro-inflammatory cytokines (except for IFN-gamma). Probiotic may modify intestinal microenvironment resulting in a decline in pro-inflammatory cytokines. TRIAL REGISTRATION: NCT03782428; retrospectively registered on 20th December 2018.

Reviewing the role of progesterone therapy in endometriosis.

Endometriosis is a benign, chronic inflammatory condition characterized by the presence and growth of endometrial implants outside the uterine cavity. The cause of endometriosis is multifactorial. It is due to the diversity of hypothesis and plausibility of hormonal alterations which could play a major role. Evidence has shown that progesterone resistance is a key factor for endometriosis sufferers. Medical therapy can avoid surgical intervention, which may lead to a reduced in ovarian reserve, and its effects of earlier menopause and reduced fecundity. Progesterone receptor isoform has provided new insight as the potential treatment. Progestin, anti-progestin and selective progesterone receptor modulators usage, which target these receptors, could avoid hypo-estrogenic side effects, which can be debilitating. Numerous types of these medications have been used on and off labeled to treat endometriosis with varying success. This review aims to consolidate series of clinical trials using progestins in endometriosis.

A four-decade analysis of the incidence trends, sociodemographic and clinical characteristics of inflammatory bowel disease patients at single tertiary centre, Kuala Lumpur, Malaysia.

BACKGROUND: Inflammatory bowel disease (IBD) was once considered as a Western disease. However, recent epidemiological data showed an emerging trend of IBD cases in the Eastern Asia countries. Clinico-epidemiological data of IBD in Malaysia is scarce. This study aimed to address this issue. METHODS: Retrospective analysis of ulcerative colitis (UC) and Crohn's disease (CD), diagnosed from January 1980 till June 2018 was conducted at our centre. RESULTS: A total of 413 IBD patients (281 UC, 132 CD) were identified. Mean crude incidence of IBD has increased steadily over the first three decades: 0.36 (1980-1989), 0.48 (1990-1999) and 0.63 per 100,000 person-years (2000-2009). In the 2010 to 2018 period, the mean crude incidence has doubled to 1.46 per 100,000 person-years. There was a significant rise in the incidence of CD, as depicted by reducing UC:CD ratio: 5:1 (1980-1989), 5:1 (1990-1999), 1.9:1 (2000-2009) and 1.7:1 (2010-2018). The prevalence rate of IBD, UC and CD, respectively were 23.0, 15.67 and 7.36 per 100,000 persons. Of all IBD patients, 61.5% (n = 254) were males. When stratified according to ethnic group, the highest prevalence of IBD was among the Indians: 73.4 per 100,000 persons, followed by Malays: 24.8 per 100,000 persons and Chinese: 14.6 per 100,000 persons. The mean age of diagnosis was 41.2 years for UC and 27.4 years for CD. Majority were non-smokers (UC: 76.9%, CD: 70.5%). The diseases were classified as follows: UC; proctitis (9.2%), left-sided colitis (50.2%) and extensive colitis (40.6%), CD; isolated ileal (22.7%), colonic (28.8%), ileocolonic (47.7%) and upper gastrointestinal (0.8%). 12.9% of CD patients had concurrent perianal disease. Extra intestinal manifestations were observed more in CD (53.8%) as compared to UC (12%). Dysplasia and malignancy, on the other hand, occurred more in UC (4.3%, n = 12) than in CD (0.8%, n = 1). Over one quarter (27.3%) of CD patients and 3.6% of UC patients received biologic therapy. CONCLUSION: The incidence of IBD is rising in Malaysia, especially in the last one decade. This might be associated with the urbanization and changing diets. Public and clinicians' awareness of this emerging disease in Malaysia is important for the timely detection and management.

The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study.

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.

γ-Tocotrienol and 6-Gingerol in Combination Synergistically Induce Cytotoxicity and Apoptosis in HT-29 and SW837 Human Colorectal Cancer Cells.

Numerous bioactive compounds have cytotoxic properties towards cancer cells. However, most studies have used single compounds when bioactives may target different pathways and exert greater cytotoxic effects when used in combination. Therefore, the objective of this study was to determine the anti-proliferative effect of γ-tocotrienol (γ-T3) and 6-gingerol (6G) in combination by evaluating apoptosis and active caspase-3 in HT-29 and SW837 colorectal cancer cells. MTS assays were performed to determine the anti-proliferative and cytotoxicity effect of γ-T3 (0-150 µg/mL) and 6G (0-300 µg/mL) on the cells. The half maximal inhibitory concentration (IC50) value of 6G+ γ-T3 for HT-29 was 105 + 67 µg/mL and for SW837 it was 70 + 20 µg/mL. Apoptosis, active caspase-3 and annexin V FITC assays were performed after 24 h of treatment using flow cytometry. These bioactives in combination showed synergistic effect on HT-29 (CI: 0.89 ± 0.02,) and SW837 (CI: 0.79 ± 0.10) apoptosis was increased by 21.2% in HT-29 and 55.4% in SW837 (p < 0.05) after 24 h treatment, while normal hepatic WRL-68 cells were unaffected. Increased apoptosis by the combined treatments was also observed morphologically, with effects like cell shrinkage and pyknosis. In conclusion, although further studies need to be done, γ-T3 and 6G when used in combination act synergistically increasing cytotoxicity and apoptosis in cancer cells.

Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells.

BACKGROUND: Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment. METHODS: In this study, we investigated the interaction of GTT and HC and its mode of cell death on glioma cell lines. GTT or HC alone and in combination were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) by [3-(4,5-dimethylthiazol-2- yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)- 2H- tetrazolium, inner salt] MTS assay. The interactions of each combination were evaluated by using the combination index (CI) obtained from an isobologram. RESULTS: Individually, GTT or HC displayed mild growth inhibitory effects against glioma cancer cell lines at concentration values ranging from 42-100 µg/ml and 75-119 µg/ml respectively. However, the combination of sub-lethal doses of GTT + HC dramatically enhanced the inhibition of glioma cancer cell proliferation and exhibited a strong synergistic effect on 1321N1 with CI of 0.55, and CI = 0.54 for SW1783. While in LN18 cells, moderate synergistic interaction of GTT + HC was observed with CI value of 0.73. Exposure of grade II, III and IV cells to combined treatments for 24 hours led to increased apoptosis as determined by annexin-V FITC/PI staining and caspase-3 apoptosis assay, showing caspase-3 activation of 27%, 7.1% and 79% respectively. CONCLUSION: In conclusion, combined treatments with sub-effective doses of GTT and HC resulted in synergistic inhibition of cell proliferation through the induction of apoptosis of human glioma cells in vitro.

Factors associated with placenta praevia in primigravidas and its pregnancy outcome.

AIM: To examine the factors associated with placenta praevia in primigravidas and also compare the pregnancy outcomes between primigravidas and nonprimigravidas. METHOD: A retrospective cohort study was conducted in women who underwent caesarean section for major placenta praevia in a tertiary university hospital from January 2007 till December 2013. Medical records were reviewed. RESULT: Among 243 with major placenta praevia, 56 (23.0%) were primigravidas and 187 (77.0%) were nonprimigravidas. Factors associated with placenta praevia in the primigravidas were history of assisted conception (P = 0.02) and history of endometriosis (P = 0.01). For maternal outcomes, the nonprimigravidas required earlier delivery than primigravidas (35.76 ± 2.54 weeks versus 36.52 ± 1.95 weeks, P = 0.03) and had greater blood loss (P = 0.04). A vast majority of the primigravidas had either posterior type II or type III placenta praevia. As for neonatal outcomes, the Apgar score at 1 minute was significantly lower for the nonprimigravidas (7.89 ± 1.72 versus 8.39 ± 1.288.39 ± 1.28, P = 0.02). CONCLUSION: This study highlighted that endometriosis and assisted conception were highly associated with placenta praevia in primigravida. Understanding the pregnancy outcomes of women with placenta praevia can assist clinicians in identifying patients who are at higher risk of mortality and morbidity. Identifying potential risk factors in primigravida may assist in counseling and management of such patients.

Tocotrienol-rich fraction, [6]-gingerol and epigallocatechin gallate inhibit proliferation and induce apoptosis of glioma cancer cells.

Plant bioactives [6]-gingerol (GING), epigallocatechin gallate (EGCG) and asiaticoside (AS) and vitamin E, such as tocotrienol-rich fraction (TRF), have been reported to possess anticancer activity. In this study, we investigated the apoptotic properties of these bioactive compounds alone or in combination on glioma cancer cells. TRF, GING, EGCG and AS were tested for cytotoxicity on glioma cell lines 1321N1 (Grade II), SW1783 (Grade III) and LN18 (Grade IV) in culture by the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. With the exception of AS, combinations of two compounds were tested, and the interactions of each combination were evaluated by the combination index (CI) using an isobologram. Different grades of glioma cancer cells showed different cytotoxic responses to the compounds, where in 1321N1 and LN18 cells, the combination of EGCG + GING exhibited a synergistic effect with CI = 0.77 and CI = 0.55, respectively. In contrast, all combinations tested (TRF + GING, TRF + EGCG and EGCG + GING) were found to be antagonistic on SW1783 with CI values of 1.29, 1.39 and 1.39, respectively. Combined EGCG + GING induced apoptosis in both 1321N1 and LN18 cells, as evidenced by Annexin-V FITC/PI staining and increased active caspase-3. Our current data suggests that the combination of EGCG + GING synergistically induced apoptosis and inhibits the proliferation 1321N1 and LN18 cells, but not SW1783 cells, which may be due to their different genetic profiles.

Methods for identification of the opportunistic gut mycobiome from colorectal adenocarcinoma biopsy tissues.

Colorectal cancer poses a significant threat to global health, necessitating the development of effective early detection techniques. However, the potential of the fungal microbiome as a putative biomarker for the detection of colorectal adenocarcinoma has not been extensively explored. We analyzed the viability of implementing the fungal mycobiome for this purpose. Biopsies were collected from cancer and polyp patients. The total genomic DNA was extracted from the biopsy samples by utilizing a comprehensive kit to ensure optimal microbial DNA recovery. To characterize the composition and diversity of the fungal mycobiome, high-throughput amplicon sequencing targeting the internal transcribed spacer 1 (ITS1) region was proposed. A comparative analysis revealed discrete fungal profiles among the diseased groups. Here, we also proposed pipelines based on a predictive model using statistical and machine learning algorithms to accurately differentiate colorectal adenocarcinoma and polyp patients from normal individuals. These findings suggest the utility of gut mycobiome as biomarkers for the detection of colorectal adenocarcinoma. Expanding our understanding of the role of the gut mycobiome in disease detection creates novel opportunities for early intervention and personalized therapeutic strategies for colorectal cancer.•Detailed method to identify the gut mycobiome in colorectal cancer patients using ITS-specific amplicon sequencing.•Application of machine learning algorithms to the identification of potential mycobiome biomarkers for non-invasive colorectal cancer screening.•Contribution to the advancement of innovative colorectal cancer diagnostic methods and targeted therapies by applying gut mycobiome knowledge.

A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study's aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p < 0.001). Only IBS-SD with probiotic showed a significant rise in serotonin serum levels (p < 0.05). A significantly higher life quality measures were seen in IBS-SD with probiotic, IBS-SD with placebo, and IBS-NM with placebo (p < 0.05). All groups, both placebo and probiotic, reported significant improvement in IBS severity post-intervention with a higher prevalence of remission and mild IBS (p < 0.05). Dual strains lactobacillus-containing cultured milk drink via its regulation of relevant biomarkers, is a potential anti-depressive prophylactic agent for IBS patients at risk.

The role of probiotics in improving menstrual health in women with primary dysmenorrhoea: A randomized, double-blind, placebo-controlled trial (the PERIOD study).

BACKGROUND: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea. OBJECTIVE: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea. DESIGN: Randomized placebo-controlled trial. METHODS: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment. RESULTS: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26-1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines. CONCLUSION: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings. REGISTRATION: This study is registered under ClinicalTrials.gov (NCT04119011).

Use of Probiotic in Primary DysmenorrhoeaThis study looked at whether taking probiotics (good bacteria) for 3 months could improve the quality of life and reduce pain in women with painful periods. The study found that probiotics did not significantly improve quality of life scores, but did reduce the use of painkillers and improve mental health scores. However, the probiotics did not have a significant effect on inflammatory markers in the body. More research is needed to confirm the findings.

The Effects of Probiotics on Small Intestinal Microbiota Composition, Inflammatory Cytokines and Intestinal Permeability in Patients with Non-Alcoholic Fatty Liver Disease.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (-7.9 ± 0.44, p < 0.0001) and TNF-α (-0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: -34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: -33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes.

Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review.

Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.