What Can the Gut Microbiota of Animals Teach Us about the Relationship between Nutrition and Burden of Lifestyle Diseases?

The gut microbiota performs several crucial roles in a holobiont with its host, including immune regulation, nutrient absorption, synthesis, and defense against external pathogens, significantly influencing host physiology. Disruption of the gut microbiota has been linked to various chronic conditions, including cardiovascular, kidney, liver, respiratory, and intestinal diseases. Studying how animals adapt their gut microbiota across their life course at different life stages and under the dynamics of extreme environmental conditions can provide valuable insights from the natural world into how the microbiota modulates host biology, with a view to translating these into treatments or preventative measures for human diseases. By modulating the gut microbiota, opportunities to address many complications associated with chronic diseases appear. Such a biomimetic approach holds promise for exploring new strategies in healthcare and disease management.

Is the enteric nervous system a lost piece of the gut-kidney axis puzzle linked to chronic kidney disease?

The enteric nervous system (ENS) regulates numerous functional and immunological attributes of the gastrointestinal tract. Alterations in ENS cell function have been linked to intestinal outcomes in various metabolic, intestinal, and neurological disorders. Chronic kidney disease (CKD) is associated with a challenging intestinal environment due to gut dysbiosis, which further affects patient quality of life. Although the gut-related repercussions of CKD have been thoroughly investigated, the involvement of the ENS in this puzzle remains unclear. ENS cell dysfunction, such as glial reactivity and alterations in cholinergic signaling in the small intestine and colon, in CKD are associated with a wide range of intestinal pathways and responses in affected patients. This review discusses how the ENS is affected in CKD and how it is involved in gut-related outcomes, including intestinal permeability, inflammation, oxidative stress, and dysmotility.

Amazonian Fruits for Treatment of Non-Communicable Diseases.

PURPOSE OF REVIEW: The Amazon region has a high biodiversity of flora, with an elevated variety of fruits, such as Camu-Camu (Myrciaria dúbia), Açaí (Euterpe oleracea Mart.), Tucumã (Astrocaryum aculeatum and Astrocaryum vulgare), Fruta-do-conde (Annona squamosa L.), Cupuaçu (Theobroma grandiflorum), Graviola (Annona muricata L.), Guarana (Paullinia cupana Kunth var. sorbilis), and Pitanga (Eugenia uniflora), among many others, that are rich in phytochemicals, minerals and vitamins with prominent antioxidant and anti-inflammatory potential. RECENT FINDINGS: Studies evaluating the chemical composition of these fruits have observed a high content of nutrients and bioactive compounds. Such components are associated with significant biological effects in treating various non-communicable diseases (NCDs) and related complications. Regular intake of these fruits from Amazonas emerges as a potential therapeutic approach to preventing and treating NCDs as a nutritional strategy to reduce the incidence or mitigate common complications in these patients, which are the leading global causes of death. As studies remain largely unexplored, this narrative review discusses the possible health-beneficial effects for patients with NCDs.

Effects of Cranberry Extract (Vaccinium macrocarpon) Supplementation on Lipid Peroxidation and Inflammation in Patients with Chronic Kidney Disease (Stages 3-4): A Randomized Controlled Trial.

Background: Growing evidence suggests that bioactive compounds in berry fruits may mitigate inflammation in patients with chronic kidney disease (CKD). Objectives: To evaluate cranberry (Vaccinium macrocarpon) supplementation effects on modulation of transcription factors involved in inflammation and oxidative stress in nondialysis (stages 3 and 4) patients with CKD. Design/Participants. A randomized, double-blind, placebo-controlled study was performed with 30 patients to receive capsules containing cranberry extract (1000 mg/day) or placebo (1000 mg/day of corn starch) for two months. Measurements. The mRNA expression of nuclear factor-erythroid 2-related factor-2 (Nrf2) and nuclear factor-kB (NF-kB) was evaluated in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction. Thiobarbituric acid reactive substances (TBARS) were measured in the plasma to assess oxidative stress. Interleukin-6 (IL-6) plasma levels were assessed by enzyme-linked immunosorbent assay and C-reactive protein (CRP) by immunoturbidimetric method. Results: Twenty-five patients completed the study: 12 in the cranberry group (56.7 ± 7.5 years and body mass index (BMI) of 29.6 ± 5.5 kg/m2) and 13 in the placebo group (58.8 ± 5.1 years and BMI 29.8 ± 5.4 kg/m2). There were no differences in NF-kB or Nrf2 mRNA expressions (p = 0.99 and p = 0.89) or TBARS, CRP, and IL-6 plasma levels after cranberry supplementation. Conclusions: The cranberry extract administration (1000 mg/day) did not affect Nrf2 and NF-kB mRNA expression, oxidative stress, or inflammatory markers levels in nondialysis CKD patients. This trial is registered with NCT04377919.

Sulforaphane upregulates the mRNA expression of NRF2 and NQO1 in non-dialysis patients with chronic kidney disease.

Sulforaphane (SFN), found in cruciferous vegetables, is a known activator of NRF2 (master regulator of cellular antioxidant responses). Patients with chronic kidney disease (CKD) present an imbalance in the redox state, presenting reduced expression of NRF2 and increased expression of NF-κB. Therefore, this study aimed to evaluate the effects of SFN on the mRNA expression of NRF2, NF-κB and markers of oxidative stress in patients with CKD. Here, we observed a significant increase in the mRNA expression of NRF2 (p = 0.02) and NQO1 (p = 0.04) in the group that received 400 µg/day of SFN for 1 month. Furthermore, we observed an improvement in the levels of phosphate (p = 0.02), glucose (p = 0.05) and triglycerides (p = 0.02) also in this group. On the other hand, plasma levels of LDL-c (p = 0.04) and total cholesterol (p = 0.03) increased in the placebo group during the study period. In conclusion, 400 µg/day of SFN for one month improves the antioxidant system and serum glucose and phosphate levels in non-dialysis CKD patients.

Production of Toxins by the Gut Microbiota: The Role of Dietary Protein.

PURPOSE OF REVIEW: This narrative review will discuss how the intake of specific protein sources (animal and vegetable) providing specific amino acids can modulate the gut microbiota composition and generate toxins. A better understanding of these interactions could lead to more appropriate dietary recommendations to improve gut health and mitigate the risk of complications promoted by the toxic metabolites formed by the gut microbiota. RECENT FINDINGS: Gut microbiota is vital in maintaining human health by influencing immune function and key metabolic pathways. Under unfavorable conditions, the gut microbiota can produce excess toxins, which contribute to inflammation and the breakdown of the integrity of the intestinal barrier. Genetic and environmental factors influence gut microbiota diversity, with diet playing a crucial role. Emerging evidence indicates that the gut microbiota significantly metabolizes amino acids from dietary proteins, producing various metabolites with beneficial and harmful effects. Amino acids such as choline, betaine, l-carnitine, tyrosine, phenylalanine, and tryptophan can increase the production of uremic toxins when metabolized by intestinal bacteria. The type of food source that provides these amino acids affects the production of toxins. Plant-based diets and dietary fiber are associated with lower toxin formation than animal-based diets due to the high amino acid precursors in animal proteins.

Using the concept of food as medicine to mitigate inflammation in patients undergoing peritoneal dialysis.

The most common kidney replacement therapy (KRT) worldwide is hemodialysis (HD), and only 5%-10% of patients are prescribed peritoneal dialysis (PD) as KRT. Despite PD being a different method, these patients also present particular complications, such as oxidative stress, gut dysbiosis, premature aging, and mitochondrial dysfunction, leading to an inflammation process and high cardiovascular mortality risk. Although recent studies have reported nutritional strategies in patients undergoing HD with attempts to mitigate these complications, more information must be needed for PD patients. Therefore, this review provides a comprehensive analysis of recent studies of nutritional intervention to mitigate inflammation in PD patients.

Vitamin E and conflicting understandings in noncommunicable diseases: Is it worth supplementing?

Vitamin E is a lipid-soluble nutrient found mainly in vegetable oils and oilseeds. It is divided into eight homologous compounds; however, only α-tocopherol exhibits vitamin activity. Many advantages are related to these compounds, including cellular protection through antioxidant and anti-inflammatory activity, and improving lipid metabolism. Physiopathology of many diseases incepts with reduced antioxidant defense, characterized by an increased reactive oxygen species production and activation of transcription factors involved in inflammation, such as nuclear factor-kappa B (NF-κB), that can be linked to oxidative stress. Moreover, disorders of lipid metabolism can increase the risk of cardiovascular diseases. In addition, intestinal dysbiosis plays a vital role in developing chronic non-communicable diseases. In this regard, vitamin E can be considered to mitigate those disorders, but data still needs to be more conclusive. This narrative review aims to elucidate the mechanisms of action of vitamin E and if supplementation can be beneficial in a disease scenario regarding non-communicable diseases.

Can curcumin supplementation break the vicious cycle of inflammation, oxidative stress, and uremia in patients undergoing peritoneal dialysis?

BACKGROUND & AIMS: Turmeric (a source of curcumin) is an excellent food to modulate oxidative stress, inflammation, and gut dysbiosis in patients with chronic kidney disease (CKD). However, no studies report the benefits of curcumin in patients undergoing peritoneal dialysis (PD). This study aims to evaluate the effects of curcuminoid supplementation on oxidative stress, inflammatory markers, and uremic toxins originating from gut microbiota in patients with CKD undergoing PD. METHODS: This longitudinal, randomized, single-blind, placebo-controlled trial evaluated 48 patients who were randomized into two groups: Curcumin (three capsules of 500 mg of Curcuma longa extract, with 98.42 % total curcuminoids) or placebo (three capsules of 500 mg of starch) for twelve weeks. In the peripheral blood mononuclear cells (PBMCs), the transcriptional expression levels of Nrf2, HOX-1 and NF-κB were evaluated by quantitative real-time PCR. Oxidative stress was evaluated by malondialdehyde (MDA) and total Thiol (T-SH). TNF-α and IL-6 plasma levels were measured by ELISA. P-cresyl sulphate plasma level, a uremic toxin, was evaluated by high-performance liquid chromatography (HPLC) with fluorescent detection. RESULTS: Twenty-four patients finished the study: 10 in the curcumin group (57.5 ± 11.6 years) and 14 in the placebo group (56.5 ± 10.0 years). The plasma levels of MDA were reduced after 12 weeks in the curcumin group (p = 0.01), while the placebo group remained unchanged. However, regarding the difference between the groups at the endpoint, no change was observed in MDA. Still, there was a trend to reduce the p-CS plasma levels in the curcumin group compared to the placebo group (p = 0.07). Likewise, the concentrations of protein thiols, mRNA expression of Nrf2, HOX-1, NF-κB, and cytokines plasma levels did not show significant changes. CONCLUSION: Curcuminoid supplementation for twelve weeks attenuates lipid peroxidation and might reduce uremic toxin in patients with CKD undergoing PD. This study was registered on Clinicaltrials.gov as NCT04413266.

Sulforaphane Supplementation Did Not Modulate NRF2 and NF-kB mRNA Expressions in Hemodialysis Patients.

BACKGROUND: Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD. OBJECTIVE: The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD). DESIGN AND METHODS: A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation. RESULTS: Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers. CONCLUSION: 150 µmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD.

Serum Magnesium Levels in Patients with Chronic Kidney Disease: Is There a Relationship with Inflammation Status?

BACKGROUND: Magnesium (Mg2+) is a fundamental mineral that maintains cellular function, and low levels may be linked to inflammation in patients with chronic kidney disease (CKD). This cross-sectional study evaluated the correlation between serum Mg2+ levels and the inflammatory status in patients undergoing dialysis. METHODS: Two hundred patients with CKD [150 undergoing hemodialysis (HD), 50 (18) years; BMI 24 (4.8) kg/m²; and 50 patients on peritoneal dialysis (PD), 54 (17.7) years; BMI, 27.5 (7.3) kg/m²] were included. Serum Mg2+ levels were evaluated using a colourimetric test and commercial kit. Inflammatory markers were assessed by ELISA and multiplex bead-based assay. Lipid peroxidation was evaluated using thiobarbituric acid-reactive substances. RESULTS: The median serum Mg2+ levels were 2.3 (0.5) mg/dL, and 21% of patients presented Mg2+ deficiency (< 2.07 mg/dL or 0.85 mmol/L). We found no difference in Mg2+ serum levels between the two groups. A significant negative correlation was observed between serum Mg2+ levels and plasma hs-CRP (r =-0.17, p = 0.01), IL-8 (r =-0.35, p = 0.01), and MCP-1 (r =-0.31, p = 0.03) levels. CONCLUSION: Mg2+ serum levels were negatively correlated with inflammatory status in patients with CKD on dialysis.

Blueberry, cranberry, raspberry, and strawberry as modulators of the gut microbiota: target for treatment of gut dysbiosis in chronic kidney disease? From current evidence to future possibilities.

Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.

Is Trimethylamine N-oxide (TMAO) Associated with NF-κB mRNA Expression in Patients with Coronary Artery Disease?

Abstract Background: Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, is associated with cardiovascular disease (CVD) development. TMAO can trigger an inflammatory response by inducing the nuclear factor-kappa B (NF-κB) signaling cascade and increasing the expression of pro-inflammatory cytokines, contributing to the worsening of CVD. This study aimed to evaluate the association between TMAO plasma levels and inflammation in patients with coronary artery disease (CAD). Methods: A cross-sectional study was carried out including 29 patients with CAD. Peripheral blood mononuclear cells (PBMC) were isolated from fasting blood samples, and NF-κB and vascular cell adhesion protein 1 (VCAM1) mRNA expression were estimated using real-time quantitative PCR. We determined TMAO plasma levels by LC-MS/MS and TNF-α by ELISA. Routine biochemical parameters were evaluated using an automatic biochemical analyzer. Correlations were estimated by Spearman or Pearson test. Statistical significance was set at the level of p < 0.05. Results: All patients presented TMAO levels within the normal range according to EUTox (normal range: 2.83 ± 1.53 mg/L; CAD patients: 0.2 [0.1 to 0.2] ng/μL). TMAO plasma levels were positively correlated with NF-κB mRNA expression (0.555; p = 0.002). Conclusion: TMAO plasma levels may be associated with NF-κB mRNA expression in patients with CAD and may contribute to the pathogenesis of this disease.

Effects of Probiotic-Enriched Minas Cheese (Lactobacillus acidophilus La-05) on Cardiovascular Parameters in 5/6 Nephrectomized Rats.

Dairy foods have become an interest in chronic kidney disease (CKD) due to their nutritional profile, which makes them a good substrate for probiotics incorporation. This study evaluated the effect of probiotic-enriched Minas cheese with Lactobacillus acidophilus La-05 in an experimental rat model for CKD on cardiac, inflammatory, and oxidative stress parameters. Male Wistar rats were divided into 4 groups (n = 7/group): 5/6 nephrectomy + conventional Minas cheese (NxC); 5/6 nephrectomy + probiotic Minas cheese (NxPC); Sham + conventional Minas cheese (ShamC); Sham + probiotic Minas cheese (ShamPC). Offering 20 g/day of Minas cheese with Lact. acidophilus La-05 (108-109 log CFU/g) for 6 weeks. The cardiomyocyte diameter was determined. Superoxide dismutase (SOD) activity in plasma, heart, kidney, and colon tissue was performed. At the end of supplementation, no significant changes in lipid profile and renal parameters were found. The NxPC group showed a decrease in cardiomyocyte diameter compared to the NxC group (16.99 ± 0.85 vs. 19.05 ± 0.56 µm, p = 0.0162); also they showed reduced plasmatic SOD activity (502.8 ± 49.12 vs. 599.4 ± 94.69 U/mL, p < 0.0001). In summary, probiotic-enriched Minas cheese (Lact. acidophilus La-05) consumption suggests a promisor cardioprotective effect and was able to downregulate SOD activity in a rat model of CKD.

Protect the Kidneys and Save the Heart Using the Concept of Food as Medicine.

Chronic kidney disease is a significant risk factor for cardiovascular disease. In addition to traditional risk factors, such as hypertension, dyslipidemia, diabetes and smoking, patients with chronic kidney disease have a uremic phenotype marked by premature aging, mitochondrial dysfunction, persistent low-grade inflammation, gut dysbiosis and oxidative stress. These complications contribute to abnormal vascular and myocardial remodeling processes, resulting in accelerated vascular calcification, cellular and organ senescence and a high risk of cardiovascular disease. Nonpharmacological strategies, such as increasing physical activity and a healthy diet, may slow the progression of kidney disease and consequently protect the heart. Thus, a deep promotion and advocacy of nutritional guidance based on scientific data is needed. This narrative review discusses how nutritional interventions may delay progressive organ damage in the kidney-heart axis.

A normative microbiome is not restored following kidney transplantation.

Dialysis and kidney transplantation (Ktx) mitigate some of the physiological deficits in chronic kidney disease (CKD), but it remains to be determined if these mitigate microbial dysbiosis and the production of inflammatory microbial metabolites, which contribute significantly to the uraemic phenotype. We have investigated bacterial DNA signatures present in the circulation of CKD patients and those receiving a KTx. Our data are consistent with increasing dysbiosis as CKD progresses, with an accompanying increase in trimethylamine (TMA) producing pathobionts Pseudomonas and Bacillus. Notably, KTx patients displayed a significantly different microbiota compared with CKD5 patients, which surprisingly included further increase in TMA producing Bacillus and loss of salutogenic Lactobacilli. Only two genera (Viellonella and Saccharimonidales) showed significant differences in abundance following KTx that may reflect a reciprocal relationship between TMA producers and utilisers, which supersedes restoration of a normative microbiome. Our metadata analysis confirmed that TMA N-oxide (TMAO) along with one carbon metabolism had significant impact upon both inflammatory burden and the composition of the microbiome. This indicates that these metabolites are key to shaping the uraemic microbiome and might be exploited in the development of dietary intervention strategies to both mitigate the physiological deficits in CKD and enable the restoration of a more salutogenic microbiome.

Targeting the Gut Microbiota in Kidney Disease: The Future in Renal Nutrition and Metabolism.

There is increasing interest in the therapeutic potential of manipulating the gut microbiome of patients with chronic kidney disease (CKD). This is because there is a substantial deviation from a balanced gut microbiota profile in CKD, with many deleterious downstream effects. Nutritional interventions such as plant-based diets with reduced animal protein intake and the use of probiotics, prebiotics, and synbiotics may alter the microbiome. This article aims to briefly describe what is known about the gut microbiome in patients with CKD, factors contributing to gut dysbiosis, and outline important evidence gaps. Future potential therapies, including restoring the microbiota with food and microbiota-based and metabolomic-based therapies, are also discussed.

COVID-19 and Nutrition: Focus on Chronic Kidney Disease.

Some chronic diseases, including chronic kidney disease (CKD), may be associated with poor outcomes, including a high rate of hospitalization and death after COVID-19 infection. In addition to the vaccination program, diet intervention is essential for boosting immunity and preventing complications. A healthy diet containing bioactive compounds may help mitigate inflammatory responses and oxidative stress caused by COVID-19. In this review, we discuss dietary interventions for mitigating COVID-19 complications, including in persons with CKD, which can worsen COVID-19 symptoms and its clinical outcomes, while diet may help patients with CKD to resist the ravages of COVID-19 by improving the immune system, modulating gut dysbiosis, mitigating COVID-19 complications, and reducing hospitalization and mortality. The concept of food as medicine, also known as culinary medicine, for patients with CKD can be extrapolated to COVID-19 infection because healthy foods and nutraceuticals have the potential to exert an important antiviral, anti-inflammatory, and antioxidant role.

Royal jelly: a predictive, preventive and personalised strategy for novel treatment options in non-communicable diseases.

Royal jelly (RJ) is a bee product produced by young adult worker bees, composed of water, proteins, carbohydrates and lipids, rich in bioactive components with therapeutic properties, such as free fatty acids, mainly 10-hydroxy-trans-2-decenoic acid (10-H2DA) and 10-hydroxydecanoic acid (10-HDA), and major royal jelly proteins (MRJPs), as well as flavonoids, most flavones and flavonols, hormones, vitamins and minerals. In vitro, non-clinical and clinical studies have confirmed its vital role as an antioxidant and anti-inflammatory. This narrative review discusses the possible effects of royal jelly on preventing common complications of non-communicable diseases (NCDs), such as inflammation, oxidative stress and intestinal dysbiosis, from the viewpoint of predictive, preventive and personalised medicine (PPPM/3PM). It is concluded that RJ, predictively, can be used as a non-pharmacological therapy to prevent and mitigate complications related to NCDs, and the treatment must be personalised.