Kefir and Intestinal Microbiota Modulation: Implications in Human Health

In the last decades changes in the pattern of health and disease in Latin America and in the world has been observed, with an increase in cases of chronic non-communicable diseases. Changes in intestinal microbiota composition can contribute to the development of these diseases and be useful in their management. In this context, the consumption of fermented foods with probiotic properties, such as kefir, stands out due to its gut microbiota-modulating capacity. There is an increasing interest in the commercial use of kefir since it can be marketed as a natural beverage containing health-promoting bacteria and has been gaining international popularity in Latin America. Also the consumption of these drinks in Latin America seems to be even more relevant, given the socioeconomic situation of this population, which highlights the need for disease prevention at the expense of its treatment. In this narrative review, we discuss how kefir may work against obesity, diabetes mellitus, liver disease, cardiovascular disorders, immunity, and neurological disorders. Peptides, bioactive compounds and strains occurring in kefir, can modulate gut microbiota composition, low-grade inflammation and intestinal permeability, which consequently may generate health benefits. Kefir can also impact on the regulation of organism homeostasis, with a direct effect on the gut-brain axis, being a possible strategy for the prevention of metabolic diseases. Further studies are needed to standardize these bioactive compounds and better elucidate the mechanisms linking kefir and intestinal microbiota modulation. However, due to the benefits reported, low cost and ease of preparation, kefir seems to be a promising approach to prevent and manage microbiota-related diseases in Latin America and the rest of the world.

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Fructose-Induced Intestinal Microbiota Shift Following Two Types of Short-Term High-Fructose Dietary Phases

Nutrients ◽

10.3390/nu12113444 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3444

Author(s):

Julia Beisner ◽

Anita Gonzalez-Granda ◽

Maryam Basrai ◽

Antje Damms-Machado ◽

Stephan C. Bischoff

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Metabolic Diseases ◽

Plasma Cholesterol ◽

Fecal Microbiota ◽

Adult Women ◽

Microbiota Composition ◽

Short Term ◽

High Consumption ◽

High Fructose

High consumption of fructose and high-fructose corn syrup is related to the development of obesity-associated metabolic diseases, which have become the most relevant diet-induced diseases. However, the influences of a high-fructose diet on gut microbiota are still largely unknown. We therefore examined the effect of short-term high-fructose consumption on the human intestinal microbiota. Twelve healthy adult women were enrolled in a pilot intervention study. All study participants consecutively followed four different diets, first a low fructose diet (< 10 g/day fructose), then a fruit-rich diet (100 g/day fructose) followed by a low fructose diet (10 g/day fructose) and at last a high-fructose syrup (HFS) supplemented diet (100 g/day fructose). Fecal microbiota was analyzed by 16S rRNA sequencing. A high-fructose fruit diet significantly shifted the human gut microbiota by increasing the abundance of the phylum Firmicutes, in which beneficial butyrate producing bacteria such as Faecalibacterium, Anareostipes and Erysipelatoclostridium were elevated, and decreasing the abundance of the phylum Bacteroidetes including the genus Parabacteroides. An HFS diet induced substantial differences in microbiota composition compared to the fruit-rich diet leading to a lower Firmicutes and a higher Bacteroidetes abundance as well as reduced abundance of the genus Ruminococcus. Compared to a low-fructose diet we observed a decrease of Faecalibacterium and Erysipelatoclostridium after the HFS diet. Abundance of Bacteroidetes positively correlated with plasma cholesterol and LDL level, whereas abundance of Firmicutes was negatively correlated. Different formulations of high-fructose diets induce distinct alterations in gut microbiota composition. High-fructose intake by HFS causes a reduction of beneficial butyrate producing bacteria and a gut microbiota profile that may affect unfavorably host lipid metabolism whereas high consumption of fructose from fruit seems to modulate the composition of the gut microbiota in a beneficial way supporting digestive health and counteracting harmful effects of excessive fructose.

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Combined effects of Scutellaria baicalensis with metformin on glucose tolerance of patients with type 2 diabetes via gut microbiota modulation

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00221.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. E52-E61

Author(s):

Na Rae Shin ◽

Namyi Gu ◽

Han Seok Choi ◽

Hojun Kim

Keyword(s):

Type 2 Diabetes ◽

Placebo Group ◽

Glucose Tolerance ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Metabolic Diseases ◽

Scutellaria Baicalensis ◽

Rrna Gene ◽

Microbiota Composition

Metformin is a widely prescribed antidiabetic agent, whereas Scutellaria baicalensis (SB) is a commonly used medicinal herb for treatment of type 2 diabetes (T2D). Gut microbiota is involved in pathophysiology of metabolic diseases including T2D, and intestinal microbiota may be one of the important therapeutic targets for the ailment. This study was conducted to investigate the effects of SB combined with metformin on treatment of T2D while evaluating changes in the gut microbiota composition. Patients with T2D were randomized into control and treatment groups. Subjects who had already been prescribed metformin were allotted to additional SB (3.52 g/day) group or placebo group. The initial treatment session was 8 wk, and after washout period for 4 wk they were crossed over to the opposite treatment for another 8 wk. The influence of SB and placebo on the intestinal microbiota was analyzed by MiSeq system based on 16S rRNA gene. Glucose tolerance was lower in the SB group than the placebo group. Similarly, the relative RNA expression of TNF-α was significantly reduced after SB treatment. SB treatment influenced the gut microbiota, especially Lactobacillus and Akkermansia, which showed remarkable increases after SB treatment. Some subjects showed high liver enzyme levels after SB treatment, and their microbiota composition at baseline differed with subjects whose liver enzymes were not affected. We also predicted that selenocompound metabolism was increased and naphthalene degradation was decreased after SB treatment. These results suggest that SB with metformin treatment may improve the glucose tolerance and inflammation and influence the gut microbiota community in T2D.

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Gut microbiota composition and arterial stiffness measured by pulse wave velocity: case–control study protocol (MIVAS study)

BMJ Open ◽

10.1136/bmjopen-2020-038933 ◽

2021 ◽

Vol 11 (2) ◽

pp. e038933

Author(s):

Rita Salvado ◽

Sandra Santos-Minguez ◽

Cristina Agudo-Conde ◽

Cristina Lugones-Sanchez ◽

Angela Cabo-Laso ◽

...

Keyword(s):

Arterial Stiffness ◽

Gut Microbiota ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Intestinal Microbiota ◽

Pulse Wave ◽

Case Control Study ◽

Case Control ◽

Microbiota Composition ◽

Control Study

IntroductionIntestinal microbiota is arising as a new element in the physiopathology of cardiovascular diseases. A healthy microbiota includes a balanced representation of bacteria with health promotion functions (symbiotes). The aim of this study is to analyse the relationship between intestinal microbiota composition and arterial stiffness.Methods and analysisAn observational case—control study will be developed. Cases will be defined by the presence of at least one of the following: carotid-femoral pulse wave velocity (cf-PWV), Cardio-Ankle Vascular Index (CAVI), brachial ankle pulse wave velocity (ba or ba-PWV) above the 90th percentile, for age and sex, of the reference population. Controls will be selected from the same population as cases. The study will be developed in Primary Healthcare Centres. We will select 500 subjects (250 cases and 250 controls), between 45 and 74 years of age. Cases will be selected from a database that combines data from EVA study (Spain) and Guimarães/Vizela study (Portugal). Measurements: cf-PWV will be measured using the SphygmoCor system, CAVI, ba-PWV and Ankle-Brachial Index will be determined using VaSera device. Gut microbiome composition in faecal samples will be determined by 16S ribosomal RNA sequencing. Lifestyle will be assessed by food frequency questionnaire, adherence to the Mediterranean diet and IPAQ (International Physical Activity Questionnaire). Body composition will be evaluated by bioimpedance.Ethics and disseminationThe study has been approved by ‘Committee of ethics of research with medicines of the health area of Salamanca’ on 14 December 2018 (cod. 2018-11-136) and the ’Ethics committee for health of Guimaraes’ (Portugal) on 15 October 2019 (ref: 67/2019). All study participants will sign an informed consent form agreeing to participate in the study, in compliance with the Declaration of Helsinki and the WHO standards for observational studies. The results of this study will allow a better description of gut microbiota in patients with arterial stiffness.Trial registration detailsClinicalTrials.gov, identifier NCT03900338

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Particle Radiation Side-Effects: Intestinal Microbiota Composition Shapes Interferon-γ-Induced Osteo-Immunogenicity

Radiation Research ◽

10.1667/rade-21-00068.1 ◽

2021 ◽

Author(s):

Irene Maier ◽

Paul M Ruegger ◽

Julia Deutschmann ◽

Thomas H. Helbich ◽

Peter Pietschmann ◽

...

Keyword(s):

Bone Marrow ◽

Small Intestine ◽

Side Effects ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Interferon Γ ◽

Microbiota Composition ◽

Particle Radiation ◽

Bacterial Indicator ◽

Radiation Induced

Microbiota can both negatively and positively impact radiation-induced bone loss. Our prior research showed that compared to mice with conventional gut microbiota (CM), mice with restricted gut microbiota (RM) reduced inflammatory tumor necrosis factor (TNF) in bone marrow, interleukin (IL)-17 in blood, and chemokine (C-C motif) ligand 20 (CCL20) in bone marrow under anti-IL-17 treatment. We showed that Muribaculum intestinale was more abundant in intestinal epithelial cells (IECs) from the small intestine of female RM mice and positively associated with augmented skeletal bone structure. Female C57BL/6J pun RM mice, which were injected with anti-IL-17 antibody one day before exposure to 1.5 Gy 28Si ions of 850 MeV/u, showed high trabecular numbers in tibiae at 6 weeks postirradiation. Irradiated CM mice were investigated for lower interferon-γ and IL-17 levels in the small intestine than RM mice. IL-17 blockage resulted in bacterial indicator phylotypes being different between both microbiota groups before and after irradiation. Analysis of the fecal bacteria were performed in relation to bone quality and body weight, showing reduced tibia cortical thickness in irradiated CM mice (–15%) vs. irradiated RM mice (–9.2%). Correlation analyses identified relationships among trabecular bone parameters (TRI-BV/TV, Tb.N, Tb.Th, Tb.Sp) and Bacteroides massiliensis, Muribaculum sp. and Prevotella denticola. Turicibacter sp. was found directly correlated with trabecular separation in anti-IL-17 treated mice, whereas an unidentified Bacteroidetes correlated with trabecular thickness in anti-IL-17 neutralized and radiation-exposed mice. We demonstrated radiation-induced osteolytic damage to correlate with bacterial indicator phylotypes of the intestinal microbiota composition, and these relationships were determined from the previously discovered dose-dependent particle radiation effects on cell proliferation in bone tissue. New translational approaches were designed to investigate dynamic changes of gut microbiota in correlation with conditions of treatment and disease as well as mechanisms of systemic side-effects in radiotherapy.

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Influence of the Intestinal Microbiota on Colonization Resistance to Salmonella and the Shedding Pattern of Naturally Exposed Pigs

mSystems ◽

10.1128/msystems.00021-19 ◽

2019 ◽

Vol 4 (2) ◽

Cited By ~ 9

Author(s):

Héctor Argüello ◽

Jordi Estellé ◽

Finola C. Leonard ◽

Fiona Crispie ◽

Paul D. Cotter ◽

...

Keyword(s):

Public Health ◽

16S Rrna ◽

Gut Microbiota ◽

Intestinal Microbiota ◽

Current Control ◽

Growing Pigs ◽

Microbiota Composition ◽

Core Microbiome ◽

The Core ◽

The Impact

ABSTRACT Salmonella colonization and infection in production animals such as pigs are a cause for concern from a public health perspective. Variations in susceptibility to natural infection may be influenced by the intestinal microbiota. Using 16S rRNA compositional sequencing, we characterized the fecal microbiome of 15 weaned pigs naturally infected with Salmonella at 18, 33, and 45 days postweaning. Dissimilarities in microbiota composition were analyzed in relation to Salmonella infection status (infected, not infected), serological status, and shedding pattern (nonshedders, single-point shedders, intermittent-persistent shedders). Global microbiota composition was associated with the infection outcome based on serological analysis. Greater richness within the microbiota postweaning was linked to pigs being seronegative at the end of the study at 11 weeks of age. Members of the Clostridia, such as Blautia, Roseburia, and Anaerovibrio, were more abundant and part of the core microbiome in nonshedder pigs. Cellulolytic microbiota (Ruminococcus and Prevotella) were also more abundant in noninfected pigs during the weaning and growing stages. Microbial profiling also revealed that infected pigs had a higher abundance of Lactobacillus and Oscillospira, the latter also being part of the core microbiome of intermittent-persistent shedders. These findings suggest that a lack of microbiome maturation and greater proportions of microorganisms associated with suckling increase susceptibility to infection. In addition, the persistence of Salmonella shedding may be associated with an enrichment of pathobionts such as Anaerobiospirillum. Overall, these results suggest that there may be merit in manipulating certain taxa within the porcine intestinal microbial community to increase disease resistance against Salmonella in pigs. IMPORTANCE Salmonella is a global threat for public health, and pork is one of the main sources of human salmonellosis. However, the complex epidemiology of the infection limits current control strategies aimed at reducing the prevalence of this infection in pigs. The present study analyzes for the first time the impact of the gut microbiota in Salmonella infection in pigs and its shedding pattern in naturally infected growing pigs. Microbiome (16S rRNA amplicon) analysis reveals that maturation of the gut microbiome could be a key consideration with respect to limiting the infection and shedding of Salmonella in pigs. Indeed, seronegative animals had higher richness of the gut microbiota early after weaning, and uninfected pigs had higher abundance of strict anaerobes from the class Clostridia, results which demonstrate that a fast transition from the suckling microbiota to a postweaning microbiota could be crucial with respect to protecting the animals.

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Nuciferine modulates the gut microbiota and prevents obesity in high-fat diet-fed rats

Experimental & Molecular Medicine ◽

10.1038/s12276-020-00534-2 ◽

2020 ◽

Vol 52 (12) ◽

pp. 1959-1975

Author(s):

Yu Wang ◽

Weifan Yao ◽

Bo Li ◽

Shiyun Qian ◽

Binbin Wei ◽

...

Keyword(s):

Lipid Metabolism ◽

Gut Microbiota ◽

Relative Abundance ◽

Metabolic Diseases ◽

Intestinal Barrier ◽

16S Rrna Gene Sequencing ◽

Fecal Microbiota ◽

Rrna Gene ◽

Low Grade ◽

Rrna Gene Sequencing

AbstractGut microbiota dysbiosis has a significant role in the pathogenesis of metabolic diseases, including obesity. Nuciferine (NUC) is a main bioactive component in the lotus leaf that has been used as food in China since ancient times. Here, we examined whether the anti-obesity effects of NUC are related to modulations in the gut microbiota. Using an obese rat model fed a HFD for 8 weeks, we show that NUC supplementation of HFD rats prevents weight gain, reduces fat accumulation, and ameliorates lipid metabolic disorders. Furthermore, 16S rRNA gene sequencing of the fecal microbiota suggested that NUC changed the diversity and composition of the gut microbiota in HFD-fed rats. In particular, NUC decreased the ratio of the phyla Firmicutes/Bacteroidetes, the relative abundance of the LPS-producing genus Desulfovibrio and bacteria involved in lipid metabolism, whereas it increased the relative abundance of SCFA-producing bacteria in HFD-fed rats. Predicted functional analysis of microbial communities showed that NUC modified genes involved in LPS biosynthesis and lipid metabolism. In addition, serum metabolomics analysis revealed that NUC effectively improved HFD-induced disorders of endogenous metabolism, especially lipid metabolism. Notably, NUC promoted SCFA production and enhanced intestinal integrity, leading to lower blood endotoxemia to reduce inflammation in HFD-fed rats. Together, the anti-obesity effects of NUC may be related to modulations in the composition and potential function of gut microbiota, improvement in intestinal barrier integrity and prevention of chronic low-grade inflammation. This research may provide support for the application of NUC in the prevention and treatment of obesity.

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MECHANISMS IN ENDOCRINOLOGY: Gut microbiota in patients with type 2 diabetes mellitus

Acta Endocrinologica ◽

10.1530/eje-14-0874 ◽

2015 ◽

Vol 172 (4) ◽

pp. R167-R177 ◽

Cited By ~ 77

Author(s):

Kristine H Allin ◽

Trine Nielsen ◽

Oluf Pedersen

Keyword(s):

Type 2 Diabetes ◽

Gut Microbiota ◽

Metabolic Diseases ◽

Short Chain Fatty Acids ◽

Intestinal Content ◽

Low Grade ◽

Bacterial Fermentation ◽

Underlying Mechanisms

Perturbations of the composition and function of the gut microbiota have been associated with metabolic disorders including obesity, insulin resistance and type 2 diabetes. Studies on mice have demonstrated several underlying mechanisms including host signalling through bacterial lipopolysaccharides derived from the outer membranes of Gram-negative bacteria, bacterial fermentation of dietary fibres to short-chain fatty acids and bacterial modulation of bile acids. On top of this, an increased permeability of the intestinal epithelium may lead to increased absorption of macromolecules from the intestinal content resulting in systemic immune responses, low-grade inflammation and altered signalling pathways influencing lipid and glucose metabolism. While mechanistic studies on mice collectively support a causal role of the gut microbiota in metabolic diseases, the majority of studies in humans are correlative of nature and thus hinder causal inferences. Importantly, several factors known to influence the risk of type 2 diabetes, e.g. diet and age, have also been linked to alterations in the gut microbiota complicating the interpretation of correlative studies. However, based upon the available evidence, it is hypothesised that the gut microbiota may mediate or modulate the influence of lifestyle factors triggering development of type 2 diabetes. Thus, the aim of this review is to critically discuss the potential role of the gut microbiota in the pathophysiology and pathogenesis of type 2 diabetes.

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Gut microbiota and energy balance: role in obesity

Proceedings of The Nutrition Society ◽

10.1017/s0029665114001700 ◽

2014 ◽

Vol 74 (3) ◽

pp. 227-234 ◽

Cited By ~ 86

Author(s):

Michael Blaut

Keyword(s):

Energy Balance ◽

Gut Microbiota ◽

Dietary Fibre ◽

Metabolic Diseases ◽

De Novo ◽

Peptide Yy ◽

Intestinal Microbiome ◽

Molar Ratio ◽

Low Grade ◽

Dietary Fibres

The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long- and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.

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Role of Dietary Lipids in Modulating Inflammation through the Gut Microbiota

Nutrients ◽

10.3390/nu11010117 ◽

2019 ◽

Vol 11 (1) ◽

pp. 117 ◽

Cited By ~ 16

Author(s):

Paul J. Wisniewski ◽

Robert A. Dowden ◽

Sara C. Campbell

Keyword(s):

Gut Microbiota ◽

Metabolic Diseases ◽

Current Knowledge ◽

Endocannabinoid System ◽

Dietary Lipids ◽

Taxonomic Resolution ◽

Low Grade ◽

Energy Regulation ◽

Microbial Dysbiosis

Inflammation and its resolution is a tenuous balance that is under constant contest. Though several regulatory mechanisms are employed to maintain homeostasis, disruptions in the regulation of inflammation can lead to detrimental effects for the host. Of note, the gut and microbial dysbiosis are implicated in the pathology of systemic chronic low-grade inflammation which has been linked to several metabolic diseases. What remains to be described is the extent to which dietary fat and concomitant changes in the gut microbiota contribute to, or arise from, the onset of metabolic disorders. The present review will highlight the role of microorganisms in host energy regulation and several mechanisms that contribute to inflammatory pathways. This review will also discuss the immunomodulatory effects of the endocannabinoid system and its link with the gut microbiota. Finally, a brief discussion arguing for improved taxonomic resolution (at the species and strain level) is needed to deepen our current knowledge of the microbiota and host inflammatory state.

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Novel Interactions Between Circulating microRNAs and Gut Microbiota Composition in Human Obesity.

10.21203/rs.3.rs-66883/v1 ◽

2020 ◽

Author(s):

Taís Silveira Assmann ◽

Amanda Cuevas-Sierra ◽

José Ignacio Riezu-Boj ◽

Fermin Milagro ◽

J Alfredo Martínez

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Target Genes ◽

Metabolic Diseases ◽

Bacterial Species ◽

Microbiota Composition ◽

Circulating Mirnas ◽

Clinical Trial Registration ◽

Body Adiposity ◽

Gut Microbiota Composition

Abstract Background: Unbalances in microRNAs (miRNA) and gut microbiota patterns have been proposed as putative factors concerning onset and development of obesity and other metabolic diseases. However, the determinants that mediate the interactions between miRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this article was to investigate possible interactions between circulating miRNAs and gut microbiota composition in obesity. Method: The analyzed sample comprised 78 subjects with obesity [cases, body mass index (BMI): 30 – 40 kg/m2] and 25 eutrophic individuals (controls, BMI £ 25 kg/m2). The expression of 96 miRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels (Exiqon). Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR (Benjamini-Hochberg test, q-value) correction was used for multiple comparison analyses.Results: A total of 26 circulating miRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p, and miR-21-5p) with Bacteroides eggerthi, and BMI levels was evidenced (r2= 0.148, P= 0.004). Those miRNAs that correlated with obesity-associated gut bacteria abundance are known to regulate target genes that participate in metabolism-related pathways, such as fatty acid degradation, carbohydrate digestion and absorption, insulin signaling, and glycerolipid metabolism. Conclusion: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating miRNAs in relation to body adiposity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts. Clinical trial registration: clinicaltrials.gov (reg. no. NCT02737267).

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