A Clustering Study of Sociodemographic Data, Dietary Patterns, and Gut Microbiota in Healthy and Breast Cancer Women Participating in the MICROMA Study.

SCOPE: This work is part of the clinical study NCT03885648 registered in ClinicalTrials.gov, aimed at studying the relationship among breast cancer, microbiota, and exposure to environmental pollutants. As a first step, we characterized and evaluated risk factors of the participants. METHODS AND RESULTS: A case-control study was designed with breast cancer (cases, n = 122) and healthy women (controls, n = 56) recruited in two hospitals of Andalusia (Southern Spain). Participants answered questionnaires of Mediterranean diet adherence and food frequency. Data were collected from medical histories and microbiota was analyzed on stool samples. Most cases (78.2%) were diagnosed as stages I and II. Cases had higher age, body mass index (BMI), glucose, cholesterol, and potassium values than controls. Cases exhibited higher adherence to the Mediterranean diet and their food consumption was closer to that dietary pattern. A hierarchical cluster analysis revealed that the Bacillota/Bacteroidota ratio was the most relevant variable in women with breast cancer, which was higher in this group compared with controls. CONCLUSION: Although cases exhibited higher adherence to the Mediterranean diet compared with controls, they presented features and microbiota alterations typical of the metabolic syndrome, probably due to their higher BMI and reflecting changes in their lifestyle around the time of diagnosis.

Specific microbiome patterns and their association with breast cancer: the intestinal microbiota as a potential biomarker and therapeutic strategy.

Breast cancer (BC) is one of the most diagnosed cancers in women. Based on histological characteristics, they are classified as non-invasive, or in situ (tumors located within the milk ducts or milk lobules) and invasive. BC may develop from in situ carcinomas over time. Determining prognosis and predicting response to treatment are essential tools to manage this disease and reduce its incidence and mortality, as well as to promote personalized therapy for patients. However, over half of the cases are not associated with known risk factors. In addition, some patients develop resistance to treatment and relapse. Therefore, it is necessary to identify new biomarkers and treatment strategies that improve existing therapies. In this regard, the role of the microbiome is being researched as it could play a role in carcinogenesis and the efficacy of BC therapies. This review aims to describe specific microbiome patterns associated with BC. For this, a literature search was carried out in PubMed database using the MeSH terms "Breast Neoplasms" and "Gastrointestinal Microbiome", including 29 publications. Most of the studies have focused on characterizing the gut or breast tissue microbiome of the patients. Likewise, studies in animal models and in vitro that investigated the impact of gut microbiota (GM) on BC treatments and the effects of the microbiome on tumor cells were included. Based on the results of the included articles, BC could be associated with an imbalance in the GM. This imbalance varied depending on molecular type, stage and grade of cancer, menopause, menarche, body mass index, and physical activity. However, a specific microbial profile could not be identified as a biomarker. On the other hand, some studies suggest that the GM may influence the efficacy of BC therapies. In addition, some microorganisms and bacterial metabolites could improve the effects of therapies or influence tumor development.

Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: The CLINMIR Pilot Study.

Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. The novel food approved by the European Commission (EFSA), dried miracle berries (DMB), contains the natural taste-modifying protein miraculin. DMB, also available as a supplement, has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed a DMB tablet or placebo daily before each main meal (breakfast, lunch, and dinner). Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: -52.8 ± 38.5/-58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25 vs. high dose: 2.17 ± 1.84 vs. placebo: 1.57 ± 1.51 points, p < 0.05). They also had higher energy intake (p = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, p = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; p = 0.004) and docosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; p = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat-free mass vs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, p = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass), and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. Clinical trial registered (NCT05486260).

Epigenetics, Microbiota, and Breast Cancer: A Systematic Review.

Breast cancer is the most frequently diagnosed cancer in women worldwide. According to recent studies, alterations in the microbiota and epigenetic modulations are risk factors for this disease. This systematic review aims to determine the possible associations between the intestinal and mammary microbial populations, epigenetic modifications, and breast cancer. To achieve this objective, we conducted a literature search in the PubMed, Web of Science, and Science Direct databases following the PRISMA guidelines. Although no results are yet available in humans, studies in mice suggest a protective effect of maternal dietary interventions with bioactive compounds on the development of breast tumors in offspring. These dietary interventions also modified the gut microbiota, increasing the relative abundance of short-chain fatty acid-producing taxa and preventing mammary carcinogenesis. In addition, short-chain fatty acids produced by the microbiota act as epigenetic modulators. Furthermore, some authors indicate that stress alters the gut microbiota, promoting breast tumor growth through epigenetic and gene expression changes in the breast tumor microenvironment. Taken together, these findings show the ability of epigenetic modifications and alterations of the microbiota associated with environmental factors to modulate the development, aggressiveness, and progression of breast cancer.

Differential Modulation of Mouse Intestinal Organoids with Fecal Luminal Factors from Obese, Allergic, Asthmatic Children.

Asthma is a multifactorial condition that can be associated with obesity. The phenotypes of asthma in lean and obese patients are different, with proinflammatory signatures being further elevated in the latter. Both obesity and asthma are associated with alterations in intestinal barrier function and immunity, and with the composition of the intestinal microbiota and food consumption. In this study, we aimed to establish an organoid model to test the hypothesis that the intestinal content of lean and obese, allergic, asthmatic children differentially regulates epithelial intestinal gene expression. A model of mouse jejunum intestinal organoids was used. A group of healthy, normal-weight children was used as a control. The intestinal content of asthmatic obese children differentially induced the expression of inflammatory and mitochondrial response genes (Tnf-tumor necrosis factor, Cd14, Muc13-mucin 13, Tff2-Trefoil factor 2 and Tff3, Cldn1-claudin 1 and 5, Reg3g-regenerating family member 3 gamma, mt-Nd1-NADH dehydrogenase 1 and 6, and mt-Cyb-mitochondrial cytochrome b) via the RAGE-advanced glycosylation end product-specific receptor, NF-κB-nuclear factor kappa b and AKT kinase signal transduction pathways. Fecal homogenates from asthmatic normal-weight and obese children induce a differential phenotype in intestinal organoids, in which the presence of obesity plays a major role.

From Non-Alcoholic Fatty Liver Disease to Liver Cancer: Microbiota and Inflammation as Key Players.

It is estimated that 25% of the world's population has non-alcoholic fatty liver disease. This disease can advance to a more severe form, non-alcoholic steatohepatitis (NASH), a disease with a greater probability of progression to cirrhosis and hepatocellular carcinoma (HCC). NASH could be characterized as a necro-inflammatory complication of chronic hepatic steatosis. The combination of factors that lead to NASH and its progression to HCC in the setting of inflammation is not clearly understood. The portal vein is the main route of communication between the intestine and the liver. This allows the transfer of products derived from the intestine to the liver and the hepatic response pathway of bile and antibody secretion to the intestine. The intestinal microbiota performs a fundamental role in the regulation of immune function, but it can undergo changes that alter its functionality. These changes can also contribute to cancer by disrupting the immune system and causing chronic inflammation and immune dysfunction, both of which are implicated in cancer development. In this article, we address the link between inflammation, microbiota and HCC. We also review the different in vitro models, as well as recent clinical trials addressing liver cancer and microbiota.

The Interplay between Microbiota and Chemotherapy-Derived Metabolites in Breast Cancer.

The most common cancer in women is breast cancer, which is also the second leading cause of death in this group. It is, however, important to note that some women will develop or will not develop breast cancer regardless of whether certain known risk factors are present. On the other hand, certain compounds are produced by bacteria in the gut, such as short-chain fatty acids, secondary bile acids, and other metabolites that may be linked to breast cancer development and mediate the chemotherapy response. Modeling the microbiota through dietary intervention and identifying metabolites directly associated with breast cancer and its complications may be useful to identify actionable targets and improve the effect of antiangiogenic therapies. Metabolomics is therefore a complementary approach to metagenomics for this purpose. As a result of the combination of both techniques, a better understanding of molecular biology and oncogenesis can be obtained. This article reviews recent literature about the influence of bacterial metabolites and chemotherapy metabolites in breast cancer patients, as well as the influence of diet.

Gut Microbiota and Breast Cancer: The Dual Role of Microbes.

Breast cancer is the most frequently diagnosed cancer and also one of the leading causes of mortality among women. The genetic and environmental factors known to date do not fully explain the risk of developing this disease. In recent years, numerous studies have highlighted the dual role of the gut microbiota in the preservation of host health and in the development of different pathologies, cancer among them. Our gut microbiota is capable of producing metabolites that protect host homeostasis but can also produce molecules with deleterious effects, which, in turn, may trigger inflammation and carcinogenesis, and even affect immunotherapy. The purpose of this review is to describe the mechanisms by which the gut microbiota may cause cancer in general, and breast cancer in particular, and to compile clinical trials that address alterations or changes in the microbiota of women with breast cancer.

Dietary Polysaccharides as Modulators of the Gut Microbiota Ecosystem: An Update on Their Impact on Health.

A polysaccharide is a macromolecule composed of more than ten monosaccharides with a wide distribution and high structural diversity and complexity in nature. Certain polysaccharides are immunomodulators and play key roles in the regulation of immune responses during the progression of some diseases. In addition to stimulating the growth of certain intestinal bacteria, polysaccharides may also promote health benefits by modulating the gut microbiota. In the last years, studies about the triad gut microbiota-polysaccharides-health have increased exponentially. In consequence, in the present review, we aim to summarize recent knowledge about the function of dietary polysaccharides on gut microbiota composition and how these effects affect host health.

Dietary Polysaccharides and Gut Microbiota Ecosystem.

The intestinal microbiota is a community of microorganisms that subsists within the gastrointestinal ecosystem [...].

Effect of Probiotics on Host-Microbiota in Bacterial Infections.

Diseases caused by bacteria cause millions of deaths every year. In addition, the problem of resistance to antibiotics is so serious that it threatens the achievements of modern medicine. This is a very important global problem as some bacteria can also develop persistence. Indeed, the persistence of pathogenic bacteria has evolved as a potent survival strategy to overcome host organisms' defense mechanisms. Additionally, chronic or persistent infections may be caused by persisters which could facilitate antibiotic resistance. Probiotics are considered good bacteria. It has been described that the modulation of gut microbiota by probiotics could have a great potential to counteract the deleterious impact and/or regulate gut microbiota after bacterial infection. Probiotics might provide health benefits through the inhibition of pathogen growth or the replacement of pathogenic bacteria. Bearing in mind that current strategies to avoid bacterial persistence and prevent antibiotic resistance are not effective, other strategies need to be assessed. We have carried out a comprehensive review, which included the reported literature between 2016 and 2021, highlighting the clinical trials that reported the probiotics' potential to regulate gut microbiota after bacterial infection and focusing in particular on the context of antibiotic resistance and persister cells.

Bifidobacterium longum subsp. infantis CECT 7210 Reduces Inflammatory Cytokine Secretion in Caco-2 Cells Cultured in the Presence of Escherichia coli CECT 515.

Previous works have described the activity of Bifidobacterium longum subsp. infantis CECT 7210 (also commercially named B. infantis IM-1®) against rotavirus in mice and intestinal pathogens in piglets, as well as its diarrhea-reducing effect on healthy term infants. In the present work, we focused on the intestinal immunomodulatory effects of B. infantis IM-1® and for this purpose we used the epithelial cell line isolated from colorectal adenocarcinoma Caco-2 and a co-culture system of human dendritic cells (DCs) from peripheral blood together with Caco-2 cells. Single Caco-2 cultures and Caco-2: DC co-cultures were incubated with B. infantis IM-1® or its supernatant either in the presence or absence of Escherichia coli CECT 515. The B. infantis IM-1® supernatant exerted a protective effect against the cytotoxicity caused by Escherichia coli CECT 515 on single cultures of Caco-2 cells as viability reached the values of untreated cells. B. infantis IM-1® and its supernatant also decreased the secretion of pro-inflammatory cytokines by Caco-2 cells and the co-cultures incubated in the presence of E. coli CECT 515, with the response being more modest in the latter, which suggests that DCs modulate the activity of Caco-2 cells. Overall, the results obtained point to the immunomodulatory activity of this probiotic strain, which might underlie its previously reported beneficial effects.

Fiber Consumption Mediates Differences in Several Gut Microbes in a Subpopulation of Young Mexican Adults.

Diet is a determinant for bodyweight and gut microbiota composition. Changes in dietary patterns are useful for the prevention and management of overweight and obesity. We aim to evaluate diet behavior and its potential association with selected gut bacteria and body weight among Mexican young adults. Mexican college students aged between 18 and 25 (normal-weight, overweight, and obese) were recruited. Anthropometric variables were recorded. A validated food frequency questionnaire was applied to all the participants. The percentages of macronutrients, fiber, and energy were calculated, and fecal samples were analyzed by real-time-qPCR to quantify selected gut bacteria. All the participants showed an unbalanced dietary pattern. However, the consumption of fruits, non-fat cereals, and oils and fats without protein were higher in the normal-weight individuals. In the overweight/obese participants, fiber intake did not correlate with the microbial variables, while Kcal from protein and Clostridium leptum correlated positively with Lactobacillus. Similarly, Clostridium coccoides-Eubacterium rectale correlated with Akkermansia muciniphila. In the normal-weight participants, Clostridium leptum and Lactobacillus correlated positively with Clostridium coccoides-Eubacterium rectale and Bifidobacterium, respectively, and Bacteroidetes negatively with Akkermansia muciniphila. In conclusion, a higher fiber intake had a positive impact on body weight and bacterial gut composition in this Mexican population of college students.

Nutrition and cellular senescence in obesity-related disorders.

Adequate nutrition is vital for immune homeostasis. However, the incidence of obesity is increasing worldwide due to the adoption of the Western diet and a sedentary lifestyle. Obesity is associated with chronic inflammation which alters the function of adipose tissue, liver, pancreas, and the nervous system. Inflammation is related to cellular senescence, distinguished by irreversible cell cycle arrest. Senescent cells secrete the senescence-associated secretory phenotype (SASP) which contains pro-inflammatory factors. Targeting processes in senescence might have a salutary approach to obesity. The present review highlights the impact of an unhealthy diet on tissues affected by obesity, and the mechanisms that promote the consequent inflammation and senescence.

Impact of Exercise on Gut Microbiota in Obesity.

Physical activity, exercise, or physical fitness are being studied as helpful nonpharmacological therapies to reduce signaling pathways related to inflammation. Studies describing changes in intestinal microbiota have stated that physical activity could increase the microbial variance and enhance the ratio of Firmicutes/Bacteroidetes, and both actions could neutralize the obesity progression and diminish body weight. The aim of this review is to provide an overview of the literature describing the relationship between physical activity profiles and gut microbiota and in obesity and some associated comorbidities. Promoting physical activity could support as a treatment to maintain the gut microbiota composition or to restore the balance toward an improvement of dysbiosis in obesity; however, these mechanisms need to be studied in more detail. The opportunity to control the microbiota by physical activity to improve health results and decrease obesity and related comorbidities is very attractive. Nevertheless, several incompletely answered questions need to be addressed before this strategy can be implemented.

Insights into Growth Factors in Liver Carcinogenesis and Regeneration: An Ongoing Debate on Minimizing Cancer Recurrence after Liver Resection.

Hepatocellular carcinoma has become a leading cause of cancer-associated mortality throughout the world, and is of great concern. Currently used chemotherapeutic drugs in the treatment of hepatocellular carcinoma lead to severe side effects, thus underscoring the need for further research to develop novel and safer therapies. Liver resection in cancer patients is routinely performed. After partial resection, liver regeneration is a perfectly calibrated response apparently sensed by the body's required liver function. This process hinges on the effect of several growth factors, among other molecules. However, dysregulation of growth factor signals also leads to growth signaling autonomy and tumor progression, so control of growth factor expression may prevent tumor progression. This review describes the role of some of the main growth factors whose dysregulation promotes liver tumor progression, and are also key in regenerating the remaining liver following resection. We herein summarize and discuss studies focused on partial hepatectomy and liver carcinogenesis, referring to hepatocyte growth factor, insulin-like growth factor, and epidermal growth factor, as well as their suitability as targets in the treatment of hepatocellular carcinoma. Finally, and given that drugs remain one of the mainstay treatment options in liver carcinogenesis, we have reviewed the current pharmacological approaches approved for clinical use or research targeting these factors.

Functions of SMYD proteins in biological processes: What do we know? An updated review.

BACKGROUND: Epigenetic modifiers, such as methyltransferases, play crucial roles in the regulation of many biological processes, including development, cancer and multiple physiopathological conditions. SUMMARY: The Su(Var)3-9, Enhancer-of-zeste and Trithorax (SET) and Myeloid, Nervy, and DEAF-1 (MYND) domain-containing (SMYD) protein family consists of five members in humans and mice (i.e. SMYD1, SMYD2, SMYD3, SMYD4 and SMYD5), which are known or predicted to have methyltransferase activity on histone and non-histone substrates. The abundance of information concerning SMYD2 and SMYD3 is of note, whereas the other members of the SMYD family have not been so thoroughly studied CONCLUSION: Here we review the literature regarding SMYD proteins published in the last five years, including basic molecular biology mechanistic studies using in vitro systems and animal models, as well as human studies with a more translational or clinical approach.