Probiotics as a strategy for addressing helminth infections in low-income countries: Working smarter rather than richer.

Helminth infections, which affect approximately 1.5 billion individuals worldwide (mainly children), are common in low- and middle-income tropical countries and can lead to various diseases. One crucial factor affecting the occurrence of these diseases is the reduced diversity of the gut microbiome due to antibiotic use. This reduced diversity compromises immune health in hosts and alters host gene expression through epigenetic mechanisms. Helminth infections may produce complex biochemical signatures that could serve as therapeutic targets. Such therapies include next-generation probiotics, live biotherapeutic products, and biochemical drug approaches. Probiotics can bind ferric hydroxide, reducing the iron that is available to opportunistic microorganisms. They also produce short-chain fatty acids associated with immune response modulation, oral tolerance facilitation, and inflammation reduction. In this review, we examine the potential link between these effects and epigenetic changes in immune response-related genes by analyzing methyltransferase-related genes within probiotic strains discussed in the literature. The identified genes were only correlated with methylation in bacterial genes. Various metabolic interactions among hosts, helminth parasites, and intestinal microbiomes can impact the immune system, potentially aiding or hindering worm expulsion through chemical signaling. Implementing a comprehensive strategy using probiotics may reduce the impact of drug-resistant helminth strains.

Health-Related Composition and Bioactivity of an Agave Sap/Prickly Pear Juice Beverage.

In this study, a beverage made from a combination of Agave sap (AS) and prickly pear juice (PPJ) was analyzed for its nutrients and bioactive and potentially health-promoting compounds. The beverage was evaluated for its ability to act as an antioxidant, regulate glycemic properties, and undergo gut bacterial fermentation in vitro. The major mono- and oligosaccharides present in the beverage were galacturonic acid (217.74 ± 13.46 mg/100 mL), rhamnose (227.00 ± 1.58 mg/100 mL), and fructose (158.16 ± 8.86 mg/mL). The main phenolic compounds identified were protocatechuic acid (440.31 ± 3.06 mg/100 mL) and catechin (359.72 ± 7.56 mg/100 mL). It was observed that the beverage had a low glycemic index (<40) and could inhibit digestive carbohydrases. The combination of ingredients also helped to reduce gas production during AS fermentation from 56.77 cm3 to 15.67 cm3. The major SCFAs produced during fermentation were butyrate, acetate, and propionate, with valerate being produced only during the late fermentation of the AS. This beverage is rich in bioactive compounds, such as polyphenols and dietary fiber, which will bring health benefits when consumed.

Intermittent fasting and high-intensity interval training do not alter gut microbiota composition in adult women with obesity.

Obesity is advancing at an accelerated pace, and yet its treatment is still an emerging field. Although studies have demonstrated the role of the microbiota in the pathogenesis of obesity, this is the first study to show the effects of intermittent fasting (IF), combined or not with exercise, and high-intensity interval training (HIIT) on the gut microbiota composition in women with obesity. Our hypothesis is that IF combined with HIIT can promote the remodeling of the composition and function of the gut microbiota. Thirty-six women with obesity, aged between 18 and 40 yr, participated in the study. They were randomly divided into three groups: 1) IF associated with HIIT group [IF + exercise group (EX), n = 15]; 2) HIIT group (EX, n = 11); and 3) IF group (IF, n = 10). Interventions took place over 8 wk, and all assessments were performed preintervention and postintervention. The HIIT circuit was performed 3 times/wk, for 25 min/session. The IF protocol was a 5:2 (2 times/wk). Multiplex analysis of inflammatory cytokines, sequencing of the 16S rRNA gene, and gas chromatography to measure fecal concentrations of short-chain fatty acids (SCFAs) were performed. This study was registered on ClinicalTrials.gov (NCT05237154). Exercise increased fecal acetate concentrations (P = 0.04), but no changes were observed in the composition and functional profile of the microbiota. The interventions did not change the composition of the microbiota, but exercise may play a modulatory role in the production of acetate. This investigation provides clinical insights into the use of IF and HIIT for women with obesity.NEW & NOTEWORTHY This is the first investigation about alternate-day fasting combined with HITT on the gut microbiota of obese women. The study contributes to the advancement of human science involving IF and HIIT, popular strategies for managing obesity. Previous evidence has explored IF in modulating the microbiota in animal models or specific populations and clinical conditions. Despite the subtle outcomes, this study has relevance and originality in the field of gut microbiota knowledge.

Potential antitumor effects of short-chain fatty acids in breast cancer models.

The effects of short-chain fatty acids (SCFAs) have been explored against cancer due to the crosstalk between gut microbiota alterations and the immune system as a crucial role in cancer development. We evaluated the SCFAs effects in both in vitro and in vivo breast cancer models. In vitro, the SCFAs displayed contrasting effects on viability index, according to the evaluation of breast cancer cells with different phenotypes, human MCF-7, SK-BR-3, MDA-MD-231, or the mouse 4T1 lineage. Acetate displayed minimal effects at concentrations up to 100 mM. Alternatively, propionate increases or reduces cell viability depending on the concentration. Butyrate and valerate showed consistent time- and concentration-dependent effects on the viability of human or mouse breast cancer cells. The selective FFA2 4-CMTB or FFA3 AR420626 receptor agonists failed to overtake the SCFA actions, except by modest inhibitory effects on MDA-MB-231 and 4T1 cell viability. The FFA2 CATPB or FFA3 and ß-hydroxybutyrate receptor antagonists lacked significant activity on human cell lines, although CATPB reduced 4T1 cell viability. Butyrate significantly affected cell morphology, clonogenicity, and migration, according to the evaluation of MDA-MB-231 and 4T1 cells. A preliminary examination of in vivo oral effects of butyrate, propionate, or valerate, dosed in prophylactic or therapeutic regimens, on several parameters evaluated in an orthotopic breast cancer model showed a reduction of lung metastasis in post-tumor induction butyrate-treated mice. Overall, the present results indicate that in vitro effects of SCFAs did not rely on FFA2 or FFA3 receptor activation, and they were not mirrored in vivo, at least at the tested conditions. Overall, the present results indicate potential in vitro inhibitory effects of SCFAs in breast cancer, independent of FFA2 or FFA3 receptor activation, and, in the metastatic breast cancer model, the butyrate-dosed therapeutic regimen reduced the number of lung metastases.

Fiber in enteral nutrition: why and what for? / La fibra en la nutrición enteral: ¿por qué y para qué?

Enteral formulas containing fiber, designed to be administered orally or by gavage, have been used for decades. Although their indication in the pediatric population does not have a global consensus, knowledge about the benefits of using fiber to promote healthier microbiota has grown in recent years. Different fiber types' physicochemical characteristics (solubility, viscosity, fermentability) determine their functions. The impact of fiber use on preventing specific chronic pathologies (cardiovascular disease, cancer, diabetes) has been reported in epidemiological studies. In controlled studies, changes in stool consistency, intestinal transit, and the composition and function of the microbiota have been observed since fiber produces fermentation metabolites such as short-chain fatty acids, which improve metabolic and immunological aspects. Different pediatric pathologies could benefit from the use of fiber.

Las fórmulas enterales que contienen fibra, diseñadas para ser administradas de forma oral o por sonda, han sido utilizadas durante décadas. Si bien su indicación en población pediátrica no cuenta con un consenso global, el conocimiento sobre los beneficios de la utilización de fibra en relación con el intestino, para promover una microbiota más saludable, ha crecido en los últimos años. Los diferentes tipos de fibra tienen características fisicoquímicas (solubilidad, viscosidad, fermentabilidad) que determinan sus funciones. El impacto del uso de fibra sobre la prevención de ciertas patologías crónicas (enfermedad cardiovascular, cáncer, diabetes) ha sido reportado en estudios epidemiológicos. En estudios controlados, se han observado cambios en la consistencia de las heces, en el tránsito intestinal y en la composición y función de la microbiota, ya que la fibra produce metabolitos de fermentación tales como ácidos grasos de cadena corta, lo cual mejora aspectos metabólicos e inmunológicos. Diferentes patologías pediátricas podrían verse beneficiadas por el uso de fibra.

Microbial determinants of dementia risk in subjects of Mexican descent with type 2 diabetes living in South Texas.

Type 2 diabetes (T2D) is a common forerunner of neurodegeneration and dementia, including Alzheimer's Disease (AD), yet the underlying mechanisms remain unresolved. Individuals of Mexican descent living in South Texas have increased prevalence of comorbid T2D and early onset AD, despite low incidence of the predisposing APOE-e4 variant and an absence of the phenotype among relatives residing in Mexico - suggesting a role for environmental factors in coincident T2D and AD susceptibility. Here, in a small clinical trial, we show dysbiosis of the human gut microbiome could contribute to neuroinflammation and risk for AD in this population. Divergent Gastrointestinal Symptom Rating Scale (GSRS) responses, despite no differences in expressed dietary preferences, provided the first evidence for altered gut microbial ecology among T2D subjects (sT2D) versus population-matched healthy controls (HC). Metataxonomic 16S rRNA sequencing of participant stool revealed a decrease in alpha diversity of sT2D versus HC gut communities and identified BMI as a driver of gut community structure. Linear discriminant analysis effect size (LEfSe) identified a significant decrease in the relative abundance of the short-chain fatty acid-producing taxa Lachnospiraceae, Faecalibacterium, and Alistipes and an increase in pathobionts Escherichia-Shigella, Enterobacter, and Clostridia innocuum among sT2D gut microbiota, as well as differentially abundant gene and metabolic pathways. These results suggest characterization of the gut microbiome of individuals with T2D could identify key actors among "disease state" microbiota which may increase risk for or accelerate the onset of neurodegeneration. Furthermore, they identify candidate microbiome-targeted approaches for prevention and treatment of neuroinflammation in AD.

Daily Cashew and Brazil Nut Consumption Modifies Intestinal Health in Overweight Women on Energy-Restricted Intervention: A Randomized Controlled Trial (Brazilian Nuts Study).

BACKGROUND: Increased intestinal permeability and dysbiosis are related to obesity. Nuts can provide nutrients and bioactive compounds that modulate gut microbiota and inflammation, enhancing the beneficial effects of weight loss. OBJECTIVES: To evaluate the effect of consuming cashew nuts (Anacardium occidentale L.) and Brazil nuts (Bertholletia excelsa H.B.K) on intestinal permeability and microbiota, fecal SCFAs and pH, inflammation, and weight loss in energy restriction condition. METHODS: In this 8-week randomized controlled trial, 40 women with overweight or obesity were assigned to energy-restricted groups (-500 kcal/d): control group (free of nuts) or Brazilian nuts group (BN: 30 g of cashew nuts and 15 g of Brazil nuts per day). Permeability was analyzed by the lactulose/mannitol test and the microbiota by sequencing the 16S gene in the V3-V4 regions. Plasma concentrations of inflammatory cytokines (TNF, IL-6, IL-10, IL-8, IL-17A) and C-reactive protein were analyzed. RESULTS: In total, 25 women completed the intervention. Both groups lost weight without statistical differences. Lactulose excretion increased only in the control group (P < 0.05). The BN consumption increased fecal propionic acid and potentially beneficial bacteria, such as Ruminococcus, Roseburia, strains NK4A214 and UCG-002 from the Ruminococcaceae family, but also Lachnospiraceae family, Bacteroides, and Lachnoclostridium, when compared to the control group. Changes in intestinal permeability were correlated to a greater reduction in body fat (kg), and IL-8, and increases in Ruminococcus abundance. CONCLUSION: Our findings demonstrate a positive impact of BN consumption within an energy-restricted context, linked to the augmentation of potentially beneficial bacteria and pathways associated with body fat reduction. Besides, BN consumption mitigated increased intestinal permeability, although its capacity to diminish permeability or enhance weight loss proved limited. This trial was registered at the Brazilian Registry of Clinical Trials as ReBEC (ID: RBR-3ntxrm).

Soluble and insoluble fibre sources in weaning piglets' diets / Fibras solúvel e insolúvel em dietas de leitões na creche

This study evaluated the effect of diets containing low levels of soluble and insoluble fiber sources on performance, diarrhea score, chemical and physical characteristics of feces, and behavior in weaning piglets. Thirty-six weaned piglets of 30 days of age with an initial body weight of 8.8 kg were distributed in 36 pens using a completely randomized design in an experimental period of 21 days. The experimental treatments were the Control diet (CONT), the Control diet + 1% beet pulp inclusion (SBP), and the Control diet + 1% lignocellulose inclusion (LCE, Arbocel®). Feed and water were available ad libitum. Body weight and feed intake were measured weekly to calculate the average daily intake, weight gain, and feed conversion ratio. The fecal consistency was determined visually twice daily, classifying feces according to three scores. To determine fecal pH and concentration of fecal short-chain fatty acids (SCFA), samples of fresh feces were collected two weeks after weaning and measured by a digital pH meter and gas chromatography, respectively. The behavior of piglets was observed once a week, using four animals per treatment, from 14:00 to 16:00, every 12 min. Fibre sources had no effect (P>0.05) on performance, except in the period 15 to 21 days after weaning, which was a tendency (P=0.061) of feed intake decrease in SBP and LCE diets. Fiber sources did not affect the fecal consistency score (P>0.05). However, piglets fed SBP and LCE showed a tendency (P<0.10) to have less diarrhea incidence 15 to 21 days post-weaning and in the entire experimental period. Fecal pH and SCFA concentration were not influenced by fiber source (P>0.05), with acetic, propionic, and butyric acids representing around 71%, 19%, and 10% of the total, respectively. Fiber sources did not influence the social and feeding behavior of weaning piglets (P>0.05). Diets containing 1% fiber sources did not alter performance, diarrhea score, fecal pH, fecal SCFA concentration, or feeding and social behavior of weaned piglets.(AU)

O estudo avaliou o efeito de dietas contendo baixos níveis de fontes de fibra solúvel e insolúvel sobre o desempenho, escore de diarreia, características químicas e físicas das fezes e comportamento de leitões desmamados. Trinta e seis leitões desmamados, com 30 dias de idade e peso vivo inicial de 8,8 kg, foram distribuídos em 36 baias, totalizando 12 repetições por tratamento, em um delineamento inteiramente casualizado. Os tratamentos experimentais foram: dieta controle (CONT), dieta controle + 1% de inclusão de polpa de beterraba (SBP) e dieta controle + 1% de inclusão de lignocelulose (LCE, Arbocel®). A ração e a água foram disponibilizadas ad libitum durante os 21 dias experimentais. O consumo médio diário de ração (CRM), ganho de peso diário (GPD) e a conversão alimentar (CA) foram medidos semanalmente. A consistência fecal foi determinada visualmente duas vezes por dia, classificando as fezes de acordo com três classificações. Amostras frescas de fezes, colhidas no 14° dia experimental, foram usadas para determinação do pH e ácidos graxos de cadeia curta (AGCC). O pH foi medido utilizando pHmetro digital, enquanto os AGCC foram determinados com auxílio de cromatografia gasosa. Para avaliar o comportamento foram observados quatro leitões por tratamento, uma vez por semana, das 14:00 às 16:00, a cada 12 minutos. As fontes de fibra não apresentaram efeito (P>0,05) sobre as variáveis de desempenho, exceto no período de 15 a 21 dias pós desmame, onde se observou uma tendência (P=0,061) de redução no consumo médio nos leitões que receberam as dietas contendo SBP e LCE. Não foi observado efeito das fontes de fibra sobre o escore de consistência fecal (P>0,05), embora leitões alimentados com SBP e LCE apresentaram uma tendência (P<0,10) de redução na incidência de diarreia no período de 15 a 21 dias pós desmame e no período total. O pH e a concentração de AGCC não foram influenciados pelas fontes de fibra (P>0,05), onde entres os tratamentos os perfis dos ácidos acético, propiônico e butírico foram semelhantes 71%, 19% e 10%, respectivamente. Não houve efeito das fontes de fibra sobre os comportamentos social e alimentar dos leitões (P>0,05). Dietas contendo 1% de fontes de fibra não alteram o desempenho, escore de diarreia, pH fecal, concentração de ácidos graxos voláteis nas fezes, bem como o comportamento alimentar e social de leitões desmamados.(AU)

Dietary replacement of soybean meal with heat-treated grain soybean in diets of feedlot-finished beef cattle: impacts on intake, digestibility, and ruminal parameters.

The objective of this study was to assess the impact of increasing levels of heat-treated soybean in the diet of crossbred cattle during the finishing phase on nutrient intake and digestibility, ruminal parameters, digesta passage rate, nitrogen balance, and microbial protein synthesis. Five steers, crossbred 7/8 Jersey x Zebu, fitted with rumen cannulas and with an average weight of 350 ± 50 kg, were utilized. The experimental treatments consisted of 0, 7, 14, 21, and 28% inclusion of heat-treated soybean in the total diet dry matter. The animals were randomly allocated in a 5 × 5 Latin square design. Evaluation of the animals took place over five experimental periods, each lasting 20 days. During each experimental period, the first 15 days were allocated for animal adaptation to the experimental diets, followed by five days of data collection. No significant differences were observed among the diets in terms of dry matter intake (average of 6.57 kg day-1; P = 0.615) and organic matter intake (average of 6.23 kg day-1; P = 0.832). However, heat-treated soybean had a significant impact on the digestibility of dry matter (P = 0.02), organic matter (P = 0.01), crude protein (P < 0.01), and neutral detergent fiber (P < 0.01). There was no observed change on microbial protein synthesis (average of 409.6 g day-1) in animals with the inclusion of heat-treated soybean in the diets. With each 1% inclusion of heat-treated soybean in the cattle diet, there was an increase of 0.00754 units in ruminal pH values and a reduction of 0.75839 mg dL-1 in ruminal ammoniacal nitrogen values. This study suggests that heat-treated soybean can be included in up to 15% of the dry matter in diets for finishing feedlot cattle.

Degenerative Cervical Myelopathy induces sex-specific dysbiosis in mice.

Degenerative Cervical Myelopathy (DCM) is the most common cause of spinal cord impairment in elderly populations. It describes a spectrum of disorders that cause progressive spinal cord compression, neurological impairment, loss of bladder and bowel functions, and gastrointestinal dysfunction. The gut microbiota has been recognized as an environmental factor that can modulate both the function of the central nervous system and the immune response through the microbiota-gut-brain axis. Changes in gut microbiota composition or microbiota-producing factors have been linked to the progression and development of several pathologies. However, little is known about the potential role of the gut microbiota in the pathobiology of DCM. Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5-6 laminae. The extent of DCM-induced changes in microbiota composition was assessed by 16S rRNA sequencing of the fecal samples. The immune cell composition was assessed using flow cytometry. To date, several bacterial members have been identified using BLAST against the largest collection of metagenome-derived genomes from the mouse gut. In both, female and males DCM caused gut dysbiosis compared to the sham group. However, dysbiosis was more pronounced in males than in females, and several bacterial members of the families Lachnospiraceae and Muribaculaceae were significantly altered in the DCM group. These changes were also associated with altered microbe-derived metabolic changes in propionate-, butyrate-, and lactate-producing bacterial members. Our results demonstrate that DCM causes dynamic changes over time in the gut microbiota, reducing the abundance of butyrate-producing bacteria, and lactate-producing bacteria to a lesser extent. Genome-scale metabolic modeling using gapseq successfully identified pyruvate-to-butanoate and pyruvate-to-propionate reactions involving genes such as Buk and ACH1, respectively. These results provide a better understanding of the sex-specific molecular effects of changes in the gut microbiota on DCM pathobiology.

Consumption of Extruded Sorghum SC319 Improved Gut Microbiota at Genus Level and Reduced Anthropometric Markers in Men with Overweight: A Randomized Controlled Clinical Trial.

BACKGROUND: Sorghum is a cereal source of energy, carbohydrates, resistant starch, proanthocyanidins, and 3-deoxyanthocyanins; it promotes satiety by slowing digestion and benefits intestinal health. OBJECTIVE: This study investigated the effects of extruded sorghum SC319 consumption on intestinal health, weight loss, and inflammatory markers in men with overweight. METHODS: This was a randomized, controlled, single-blind clinical trial. Twenty-one men were randomly allocated into one of two groups: the sorghum group (test), which received 40 g of extruded SC319 whole sorghum (n = 10), or the wheat group (control), which received 38 g of extruded whole wheat (n = 11) for eight weeks. RESULTS: The sorghum consumption increased the weight loss intragroup, decreased the body fat percentage intergroup, and did not change inflammatory markers, while the wheat group had increased IL-6 levels compared to baseline. Short-chain fatty acid production, fecal pH, and α and ß diversity indexes did not differ intra- and intergroup after interventions. However, sorghum consumption decreased genus levels of Clostridium_sensu_stricto 1, Dorea, and Odoribacter and increased CAG-873 and Turicibacter compared to baseline. Further, sorghum showed a tendency (p = 0.07) to decrease the proteobacteria phyla compared to wheat. CONCLUSION: Extruded sorghum SC319 improved intestinal microbiota and body composition and promoted weight loss, demonstrating its prebiotic potential.

Chia (Salvia hispanica L.) flour modulates the intestinal microbiota in Wistar rats fed a high-fat and high-fructose diet.

A diet rich in sugar and fat can promote metabolic disorders development, especially in the intestine. Chia flour (Salvia hispanica. L) is a source of dietary fiber, alpha-linolenic fatty acid (ALA), bioactive peptides, and phenolics, promoting health benefits. This study aimed to analyze chia flour's effect on gut microbiota modulation and intestinal health in adult male Wistar rats fed a high-fat and high-fructose (HFHF) diet. Male Wistar rats (n = 10/group) were fed the diets standard (AIN-93M) or HFHF (31% saturated fat and 20% fructose) in the first phase to induce metabolic disorders. In the second phase, the rats were fed AIN-93M, HFHF, or HFHF plus 14.7% chia flour (HFHF + CF) for 10 weeks. The consumption of chia flour increased the ALA (3.24 ± 0.24) intake and significantly improved immunoglobulin A (IgA) levels (1126.00 ± 145.90), goblet cells number (24.57 ± 2.76), crypt thickness (34.37 ± 5.86), crypt depth (215.30 ± 23.19), the longitudinal muscle layer (48.11 ± 5.04), cecum weight (4.39 ± 0.71), Shannon index (p < 0.05), and significantly increased the production of acetic (20.56 ± 4.10) and butyric acids (5.96 ± 1.50), Monoglobus sp., Lachnospiraceae sp., and Prevotellaceae sp. abundance. Furthermore, chia significantly reduced the cecal pH content (7.54 ± 1.17), body mass index (0.62 ± 0.03) and weight (411.00 ± 28.58), and Simpson index (p < 0.05). Therefore, chia intake improved intestinal health parameters and functionality in rats with metabolic disorders, which demonstrates to be an effective strategy for gut microbiota modulation.

Gut microbiota short-chain fatty acids and their impact on the host thyroid function and diseases.

Thyroid disorders are clinically characterized by alterations of L-3,5,3',5'-tetraiodothyronine (T4), L-3,5,3'-triiodothyronine (T3), and/or thyroid-stimulating hormone (TSH) levels in the blood. The most frequent thyroid disorders are hypothyroidism, hyperthyroidism, and hypothyroxinemia. These conditions affect cell differentiation, function, and metabolism. It has been reported that 40% of the world's population suffers from some type of thyroid disorder and that several factors increase susceptibility to these diseases. Among them are iodine intake, environmental contamination, smoking, certain drugs, and genetic factors. Recently, the intestinal microbiota, composed of more than trillions of microbes, has emerged as a critical player in human health, and dysbiosis has been linked to thyroid diseases. The intestinal microbiota can affect host physiology by producing metabolites derived from dietary fiber, such as short-chain fatty acids (SCFAs). SCFAs have local actions in the intestine and can affect the central nervous system and immune system. Modulation of SCFAs-producing bacteria has also been connected to metabolic diseases, such as obesity and diabetes. In this review, we discuss how alterations in the production of SCFAs due to dysbiosis in patients could be related to thyroid disorders. The studies reviewed here may be of significant interest to endocrinology researchers and medical practitioners.

Butyrate Protects Myenteric Neurons Loss in Mice Following Experimental Ulcerative Colitis.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferments dietary fibers and produces short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100 mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in the Colitis group and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in the Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in the Colitis group were attenuated in the Butyrate group. The presence of GPR41 in myenteric neurons was identified, and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

Blood orange juice intake changes specific bacteria of gut microbiota associated with cardiometabolic biomarkers.

Blood orange juice is an important source of flavanones and anthocyanins, mainly hesperidin, narirutin, and cyanidin-3-O-glucoside. The benefits of these bioactive compounds have been reported, but the mechanistic details behind their biological effects are not well established. This study investigated the effects of Moro orange (Citrus sinensis L. Osbeck) juice (MOJ) on gut microbiota composition and cardiometabolic biomarkers in overweight women. In this study, 12 overweight women (BMI from 25.0 to 29.9 kg/m2), aged 18-37 years, consumed 500 mL of MOJ every day for 4 weeks. We assessed the gut microbiota composition, levels of short-chain fatty acids (SCFAs), cardiometabolic biomarkers, and insulin resistance (HOMA-IR) at baseline and after 2 weeks and 4 weeks of MOJ intake. The results suggested that MOJ intake affected the abundance of specific operational taxonomic units (OTUs) of the gut microbiota but did not significantly alter the diversity and general composition of the gut microbiota. However, MOJ intake increased the production of SCFAs, especially propionic and isobutyric acids, and significantly improved cardiometabolic biomarkers such as blood pressure and plasma VCAM-1 levels in the overweight women. Additionally, we observed significant associations between gut microbiota OTUs belonging to the Bacteroidetes phyla and Prevotella 9 genera and the cardiometabolic biomarkers. Furthermore, MOJ reduced fasting glucose and insulin levels and HOMA-IR values, thereby enhancing insulin sensitivity in the insulin-resistant overweight women. Finally, we highlighted the importance of orange juice intake duration because some beneficial changes such as blood pressure improvements were evident at the 2-week time interval of the intervention, but other changes became significant only at the 4-week interval of MOJ intake. In conclusion, our study demonstrated that changes in specific OTUs of the gut microbiota in response to MOJ intake were associated with significant improvements in some cardiometabolic biomarkers and SCFA levels in overweight women with insulin resistance.

Dietary Supplementation with Popped Amaranth Modulates the Gut Microbiota in Low Height-for-Age Children: A Nonrandomized Pilot Trial.

Amaranth has been recognized as a nutraceutical food because it contains high-quality proteins due to its adequate amino acid composition that covers the recommended requirements for children and adults. Since pre-Hispanic times, amaranth has been consumed as popped grain; the popping process improves its nutritive quality and improves its digestibility. Popped amaranth consumption has been associated with the recovery of malnourished children. However, there is no information on the impact that popped amaranth consumption has on gut microbiota composition. A non-randomized pilot trial was conducted to evaluate the changes in composition, structure, and function of the gut microbiota of stunted children who received four grams of popped amaranth daily for three months. Stool and serum were collected at the beginning and at the end of the trial. Short-chain fatty acids (SCFA) were quantified, and gut bacterial composition was analyzed by 16S rRNA gene sequencing. Biometry and hematology results showed that children had no pathology other than low height-for-age. A decrease in the relative abundance of Alistipes putredinis, Bacteroides coprocola, and Bacteroides stercoris bacteria related to inflammation and colitis, and an increase in the relative abundance of Akkermansia muciniphila and Streptococcus thermophiles bacteria associated with health and longevity, was observed. The results demonstrate that popped amaranth is a nutritious food that helps to combat childhood malnutrition through gut microbiota modulation.

GPR43 stimulation on TCRαß+ intraepithelial colonic lymphocytes inhibits the recruitment of encephalitogenic T-cells into the central nervous system and attenuates the development of autoimmunity.

INTRODUCTION: Gut microbiota plays a critical role in the regulation of immune homeostasis. Accordingly, several autoimmune disorders have been associated with dysbiosis in the gut microbiota. Notably, the dysbiosis associated with central nervous system (CNS) autoimmunity involves a substantial reduction of bacteria belonging to Clostridia clusters IV and XIVa, which constitute major producers of short-chain fatty acids (SCFAs). Here we addressed the role of the surface receptor-mediated effects of SCFAs on mucosal T-cells in the development of CNS autoimmunity. METHODS: To induce CNS autoimmunity, we used the mouse model of experimental autoimmune encephalomyelitis (EAE) induced by immunization with the myelin oligodendrocyte glycoprotein (MOG)-derived peptide (MOG35-55 peptide). To address the effects of GPR43 stimulation on colonic TCRαß+ T-cells upon CNS autoimmunity, mucosal lymphocytes were isolated and stimulated with a selective GPR43 agonist ex vivo and then transferred into congenic mice undergoing EAE. Several subsets of lymphocytes infiltrating the CNS or those present in the gut epithelium and gut lamina propria were analysed by flow cytometry. In vitro migration assays were conducted with mucosal T-cells using transwells. RESULTS: Our results show a sharp and selective reduction of intestinal propionate at the peak of EAE development, accompanied by increased IFN-γ and decreased IL-22 in the colonic mucosa. Further analyses indicated that GPR43 was the primary SCFAs receptor expressed on T-cells, which was downregulated on colonic TCRαß+ T-cells upon CNS autoimmunity. The pharmacologic stimulation of GPR43 increased the anti-inflammatory function and reduced the pro-inflammatory features in several TCRαß+ T-cell subsets in the colonic mucosa upon EAE development. Furthermore, GPR43 stimulation induced the arrest of CNS-autoreactive T-cells in the colonic lamina propria, thus avoiding their infiltration into the CNS and dampening the disease development. Mechanistic analyses revealed that GPR43-stimulation on mucosal TCRαß+ T-cells inhibits their CXCR3-mediated migration towards CXCL11, which is released from the CNS upon neuroinflammation. CONCLUSIONS: These findings provide a novel mechanism involved in the gut-brain axis by which bacterial-derived products secreted in the gut mucosa might control the CNS tropism of autoreactive T-cells. Moreover, this study shows GPR43 expressed on T-cells as a promising therapeutic target for CNS autoimmunity.

Gut Microbiota and Its Repercussion in Parkinson's Disease: A Systematic Review in Occidental Patients.

(1) Background: Parkinson's disease (PD) is a relatively common and complex pathology, and some of its mechanisms remain to be elucidated. Change in host microbiota is related to the pathophysiology of numerous diseases. This systematic review aims to gather existing data on the occidental hemisphere, compare it, and search for any significant association between Parkinson's disease and gut microbiota dysbiosis. (2) Methods: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) and Meta-analyses Of Observational Studies in Epidemiology (MOOSE) protocols were used for this systematic review. PubMed was used as the database search engine. Of the 166 studies found, only 10 were used, as they met our inclusion criteria: case-control studies, studies that assessed the correlation of PD and gut microbiome, studies that took place in occidental regions, and studies that were performed on humans and were written in English. The Newcastle-Ottawa Scale was used as the assessment tool for overall risk of bias in this systematic review. (3) Results: The studies analyzed were divided into three geographic areas: Region 1: United States of America and Canada; Region 2: Germany, Ireland, and Finland; and Region 3: Italy; based on geographical similarities among these populations. The following statistically significant results were described in PD patients, compared with non-PD controls. In the first region, a significant increase in the following bacteria was seen: 1. Phylum: Actinobacteriota and its Genus: Bifidobacterium; 2. Phylum: Verrucomicrobiota and its Genus: Akkermansia; 3. Genus: Enterococcus, Hungatella, Lactobacillus, and Oscillospira of the Phylum: Firmicutes; 4. Family: Ruminococcaceae of Phylum: Firmicutes; 5. Phylum: Bacteroidetes and its Genus: Bacteroides; 6. Phylum: Proteobacteria. A significant decrease was described in the Family: Lachnospiraceae and its Genus: Blautia, Coprococcus, and Roseburia, which belong to the Phylum: Firmicutes. In the second region, a raised number of: 1. Phylum: Verrucomicrobiota, its Genus: Akkermansia, and its Species: Akkermansia muciniphila; 2. Family: Verrucomicrobiaceae of the Phylum: Verrucomicrobiota; 3. Genus: Lactobacillus and Roseburia of the Phylum: Firmicutes; 4. Family: Lactobacillaceae of the Phylum: Firmicutes; 5. Family: Barnesiellaceae of the Phylum: Bacteroidetes; 6. Genus: Bifidobacterium of the Phylum: Actinobacteriota; 7. Species: Bilophila wadsworthia of the Phylum: Thermodesulfobacteriota, was identified. Only one Genus: Prevotella of the Phylum: Bacteroidetes was decreased. In the third and last region, an augmented number of these bacteria were found: 1. Phylum: Verrucomicrobiota and its Genus: Akkermansia; 2. Family: Bifidobacteriaceae and Coriobacteriaceae of the Phylum: Actinobacteriota; 3. Phylum: Firmicutes and its Family: Christensenellaceae and Lactobacillaceae; 4. Family: Enterococcaceae and its Genus: Enterococcus, of the Phylum: Firmicutes; 5. Genus: Lactococcus and Oscillospira, of the Phylum: Firmicutes; 6. Phylum: Proteobacteria, its Family: Enterobacteriaceae, and the Genus: Citrobacter, Klebsiella, Salmonella, and Shigella; 7. Genus: ParaBacteroides of the Phylum: Bacteroidetes. In contrast, a significant decrease in 1. Phylum: Firmicutes, its Family: Lachnospiraceae, and its Genus: Roseburia and 2. Genus: Ruminococcus of the Phylum: Firmicutes, was described. (4) Conclusion: A significant gut dysbiosis, involving multiple bacterial taxa, was found in PD patients compared to healthy people in the occidental regions. However, more studies are needed to find the precise pathophysiologic involvement of other groups of pathogens, such as fungi and parasites, in the development and progression of PD.

Milk kefir alters fecal microbiota impacting gut and brain health in mice.

Kefir is a fermented beverage made of a symbiotic microbial community that stands out for health benefits. Although its microbial profile is still little explored, its effects on modulation of gut microbiota and production of short-chain fatty acids (SCFAs) seems to act by improving brain health. This work aimed to analyze the microbiota profile of milk kefir and its effect on metabolism, oxidative stress, and in the microbiota-gut-brain axis in a murine model. The experimental design was carried out using C57BL-6 mice (n = 20) subdivided into groups that received 0.1 mL water or 0.1 mL (10% w/v) kefir. The kefir proceeded to maturation for 48 h, and then it was orally administered, via gavage, to the animals for 4 weeks. Physicochemical, microbiological, antioxidant analyzes, and microbial profiling of milk kefir beverage were performed as well as growth parameters, food intake, serum markers, oxidative stress, antioxidant enzymes, SCFAs, and metabarcoding were analyzed in the mice. Milk kefir had 76.64 ± 0.42% of free radical scavenging and the microbiota composed primarily by the genus Comamonas. Moreover, kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (butyrate), and in the brain (butyrate and propionate). Kefir reduced triglycerides, uric acid, and affected the microbiome of animals increasing fecal butyrate-producing bacteria (Lachnospiraceae and Lachnoclostridium). Our results on the brain and fecal SCFAs and the antioxidant effect found were associated with the change in the gut microbiota caused by kefir, which indicates that kefir positively influences the gut-microbiota-brain axis and contributes to the preservation of gut and brain health. KEY POINTS: • Milk kefir modulates fecal microbiota and SCFA production in brain and colon. • Kefir treatment increases the abundance of SCFA-producing bacteria. • Milk kefir increases antioxidant enzymes and influences the metabolism of mice.

Calorie restriction mitigates metabolic, behavioral and neurochemical effects of cafeteria diet in aged male rats.

Besides metabolic dysfunctions, elderly individuals with obesity are at special risk of developing cognitive decline and psychiatric disturbances. Restricted calorie consumption could be an efficient strategy to improve metabolic function after obesity. However, its effects on anxiety-like behaviors in aged rats submitted to an obesogenic diet are unknown. For this purpose, 42 Wistar rats (18-months old) were divided into four groups: Control (CT), calorie restriction (CR), cafeteria diet (CAF), and CAF+CR (CAF/CR). CT, CR, and CAF groups received the diets for 8 weeks. CAF/CR group was submitted to the CAF menu for 7 weeks and then switched to a standard diet on a CR regimen, receiving 30% lower calories than consumed by the CT, for another 5 weeks. CAF's menu consisted of ultra-processed foods such as cookies, chocolate, sausage, and bologna. Body weight, visceral adiposity, and biochemical blood analysis were evaluated for obesity diagnosis. The profile of gut microbiota was investigated, along with circulating levels of LPS. Neurochemical parameters, such as neurotransmitter levels, were dosed. Anxiety-like behaviors were accessed using open field (OF) and elevated plus maze (EPM) tests. As expected, CR reduced weight gain and improved glucose homeostasis. Gut microbiome disturbance was found in CAF-fed animals accompanied by increased levels of LPS. However, CR after CAF mitigated several harmful responses. The obesogenic diet triggered anxiety-like manifestations in the OF and EPM tests that were not evidenced in the CAF/CR group. These findings indicate that CR can be a promising strategy for the neurological effects of obesity in aged rats.