Probiotics may have the potential to protect against breast cancer, partly through systemic immunomodulatory action and active impact upon intestinal microbiota. Given a few clinical studies on their curative role, we conducted a systematic review of the potential effects of probiotics in breast cancer patients and survivors of breast cancer, aiming to support further clinical studies. A literature search was performed using PubMed, Embase, and the CENTRAL databases from inception through to March 2022. A total of eight randomized clinical trials were identified from thirteen articles published between 2004 and 2022. We evaluated quality-of-life measures, observed bacterial species and diversity indices, probiotic-related metabolites, inflammatory biomarkers, and other responses in breast cancer patients and survivors. Results were synthesized qualitatively and quantitatively using random-effects meta-analysis. Different probiotics supplements utilized included Lactobacillus species alone (Lacto), with or without estriol; probiotic combinations of Lactobacillus with Bifidobacterium (ProLB), with or without prebiotic fructooligosaccharides (FOS); ProLB plus Streptococcus and FOS (ProLBS + FOS); and ProLB plus Enterococcus (ProLBE). We found that use of ProLBS with FOS in breast cancer patients and use of ProLBE in survivors of breast cancer show potential benefits in countering obesity and dyslipidemia. ProLBS with FOS use decreases pro-inflammatory TNF-α in breast cancer survivors and improves quality of life in those with breast-cancer-associated lymphedema. Supplementing probiotics capsules (10⁹ CFU) with a prebiotic and using an intake duration of 10 weeks could provide a better approach than probiotics alone.

Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) cases. B-cell maturation antigen (BCMA) is a key target for novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific T-cell engagers (BiTEs), which vary in efficacy, toxicity, and accessibility. To compare the efficacy and safety of BCMA-directed CAR-T therapies and BiTEs in R/R MM through a systematic review and meta-analysis. We systematically searched PubMed, Embase, and the Cochrane Library up to October 2, 2024, for studies evaluating BCMA-directed CAR-T or BiTEs therapies in R/R MM. Twenty-six studies comprising 2,246 patients were included. A random-effects meta-analysis and meta-regression were performed to assess pooled efficacy and safety outcomes and examine the impact of CAR-T constructs and patient-level characteristics. CAR-T therapies showed a higher overall response rate (ORR) of 84% and CR/stringent CR (CR/sCR) of 55%, compared to 65% and 41%, respectively, for BiTEs. Dual-targeted CAR-T therapies (e.g., anti-BCMA + anti-CD38/CD19) had the highest efficacy (ORR 92%). CAR-T was associated with more hematologic toxicity and cytokine release syndrome, while BiTEs had fewer severe events but higher infection rates. Meta-regression confirmed CAR-T significantly outperformed BiTEs. Unlike previous analyses, this study integrates interventional and real-world data, evaluates dual-target CAR-Ts, and offers detailed product- and subgroup-level comparisons. BCMA-targeted CAR-T therapies yield deeper responses but greater toxicity. BiTEs offer safer, though less potent, alternatives, supporting more personalized decisions in BCMA-directed immunotherapy for MM.

Ribosomal RNA gene amplicon sequencing is commonly used to evaluate microbiome profiles in health and disease and document the impact of interventional treatments. Nanopore sequencing is attractive since it can provide greater classification at the species level. However, optimized protocols to target marker genes for bacterial and fungal profiling are needed. To achieve an increased taxonomic resolution, we developed extraction and full-length amplicon PCR-based approaches using Nanopore sequencing. Three lysis conditions were applied to a mock microbial community, including known bacterial and fungal species: ZymoBIOMICS lysis buffer (ML) alone, incorporating bead-beating (MLB) or bead-beating plus MetaPolyzyme enzymatic treatment (MLBE). In profiling of bacteria in comparison to reference data, MLB had more statistically different bacterial phyla and genera than the other two conditions. In fungal profiling, MLB had a significant increase of Ascomycota and a decline of Basidiomycota, subsequently failing to detect Malassezia and Cryptococcus. Also, a principal coordinates analysis plot by the Bray–Curtis metric showed a significant difference among groups for bacterial (P=0.033) and fungal (P=0.012) profiles, highlighting the importance of understanding the biases present in pretreatment. Overall, microbial profiling and diversity analysis revealed that ML and MLBE are more similar than MLB for both bacteria and fungi; therefore, using this specific pipeline, bead-beating is not recommended for whole gene amplicon sequencing. However, ML alone was suggested as an optimal approach considering DNA yield, taxonomic classification, reagent cost and hands-on time. This could be an initial proof-of-concept study for simultaneous human bacterial and fungal microbiome studies.

Background Cannabis is being legalized in many countries for therapeutic and recreational purposes. The cannabinoid compounds are mainly involved in the host metabolism under the endocannabinoid system, and they regulate the intestinal microbiota via an immunomodulatory mechanism leading to obtaining positive effects on the gastrointestinal and immunological systems. Objective The review is to systematically evaluate their association and the impact of the microbiome on cannabis treatment to support further clinical trials. Methods Utilizing online sources like PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, a literature search was carried out up to July 20, 2022. The search was restricted to adults with clinical abnormalities and the use of English. An examination of predetermined subgroups under various disease conditions was carried out. The data was combined quantitatively. Result The study comprised 9 studies with 2526 participants; two were clinical trials and the others were observational studies. One significant factor influencing microbiota variation was marijuana (MJ) usage [R²=0.01, p=0.14]. In HIV patients who used MJ, there were elevated levels of Fusobacterium and Anaerotruncus and lower concentrations of Dorea. The genus Rothia was dominant, but Capnocytophaga, Fusobacterium, and Porphyromonas were low at the tongue site, whereas high Selenomonas and low Streptococcus were detected at the oral pharynx region in MJ users in oral cancer patients. Following cannabis use, Lactobacilli and S. mutan were increased in patients with musculoskeletal discomfort. Increases in the circulation of endocannabinoids are associated with an increase in SCFA-producing bacteria and a decrease in the proinflammatory species Collinsella in patients with knee arthritis. Lower Prevotella:Bacteroides ratios were more frequently linked to higher lifetime MJ consumption in those with cognitive impairments (p=0.052). Increased PEA excretion correlated with decreased microbial diversity, which caused anhedonia/amotivation to worsen. A. muciniphila was substantially more prevalent in obese patients after OEA administration. Conclusion Data from a systematic review suggest that cannabis usage and supplementation of medical cannabis in a variety of clinical problems had links with altering the human microbiome on gut, oral, rectal, and vaginal discharge. It must be taken into consideration in future research on the therapeutic effects of cannabis on patients. Short Summary As cannabis use is being legalized in more and more countries, it is important to observe how the use of cannabis affects the human body, particularly in those suffering from various clinical conditions. Using the qualitative data collected from the systematic review, it was found that cannabis use in adults with a range of different clinical conditions has associations with altering the human microbiome, a factor that must be considered in future studies of cannabis treatment for beneficial or detrimental effects on patients. Registration ID PROSPERO 2022 CRD42022354331

Background: Dysbiosis characterizes breast cancer (BC) through direct or indirect interference in a variety of biological pathways, therefore specific microbial patterns and diversity may be a biomarker for BC diagnosis and prognosis. However, there is still much to determine on the complex interplay of gut microbiome and BC. Objective: To evaluate the microbial alteration in BC patients as compared with control subjects, to explore the gut microbial modification from a range of different BC treatments, and to identify the impact of microbiome patterns on the same treatment-receiving BC patients. Methods: A literature search was conducted using electronic databases such as PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library to April 2021. The search was limited to adult BC women and the English language. A prespecified subgroup analysis in BC patients was performed. The results were synthesized quantitatively and qualitatively using random-effects meta-analysis. Results: A total of 33 studies were included in the review, accounting for 20 case-control, 8 cohort, and 5 non-randomized intervention studies. In the meta-analysis, the bacterial DNA load is reduced in the tumor compared with paired normal breast and healthy breast tissue, and interestingly, there is an inverse correlation of the bacterial load in different breast tumor stages. From the intervention studies, it revealed 41 species related to breast tumors with a predominance of Gemella haemolysans and Streptococcus mitis , and after chemotherapy, the number of species per patient was elevated by a mean of 2.6 (SD = 4.7, p = 0.052). Also, the tumor tissue showed a significant reduction of transcripts of microbial sensors such as TLR2, TLR5, and TLR9, cytoplasmic microbial sensors like NOD1 and NOD2, and the levels of BPI, MPO, and PRTN3. It found that the post-menopausal group has higher leucine-and valine-arylamidase, β-glucuronidase, and esterase-lipase activities in contrast to pre-menopausal and healthy groups. Conclusions: This systematic review elucidates the complex network of the microbiome, BC, and the therapeutic options, expecting to provide a link for stronger research studies and toward personalized medicine to improve their quality of life. Funding: None. Registration ID: PROSPERO 2021 CRD42021288186

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