Representative histology of the ileum and colon with HE stain in T2D model rats. (A) Histology of the ileum in the DM group, (B) histology of the ileum in the DM+ST group, (C) histology of the colon in the DM group, and (D) histology of the colon in the DM+ST group. The image acquisition phase was performed with a 50Â objective. Scale bar = 200 mm. In the diabetic rats, the intestinal mucosal layer was characterized by disturbed mucosal architecture, shortened villi, blunted villus tips, and inflammatory cell infiltration. In the DM+ST group, oral administration of S. thermophilus restored the normal structure of the intestinal mucosal layer. Full-size  DOI: 10.7717/peerj.7117/fig-5

Representative histology of the ileum and colon with HE stain in T2D model rats. (A) Histology of the ileum in the DM group, (B) histology of the ileum in the DM+ST group, (C) histology of the colon in the DM group, and (D) histology of the colon in the DM+ST group. The image acquisition phase was performed with a 50Â objective. Scale bar = 200 mm. In the diabetic rats, the intestinal mucosal layer was characterized by disturbed mucosal architecture, shortened villi, blunted villus tips, and inflammatory cell infiltration. In the DM+ST group, oral administration of S. thermophilus restored the normal structure of the intestinal mucosal layer. Full-size  DOI: 10.7717/peerj.7117/fig-5

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Background and aims: The link between gut microbiota and type 2 diabetes (T2D) has been addressed by numerous studies. Streptococcus thermophilus from fermented milk products, has been used as a probiotic in previous research. However, whether heat-killed S. thermophilus can improve the glycemic parameters of diabetic rats remains unanswered. In t...

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... the DM+ST group, oral administration of S. thermophilus restored the normal structure of the intestinal mucosal layer (Fig. 5). The length of villi and depth of crypts in the DM+ST group were significantly increased compared to those in DM group (Fig. ...

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... When there is a sufficient amount of SCFAs in postbiotic formulations, it can improve epithelial barrier function and protect the body from damage induced by lipopolysaccharides (Feng et al., 2018). In a T2DM rat model treated with postbiotics, heat-inactivated Streptococcus thermophilus reduced fasting blood glucose levels, glucose tolerance, and insulin resistance, and increased the abundance of beneficial bacteria such as Ruminococcaceae and Veillonella (Gao X. et al., 2019). In a randomized double-blind parallel clinical trial, compared with the placebo group, oral pasteurization of Lactobacillus griffii CP2305 significantly increased the content of bifidobacteria in the intestines of the experimental group (Sugawara et al., 2016). ...
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Diabetic nephropathy (DN) is one of the main complications of diabetes and a major cause of end-stage renal disease, which has a severe impact on the quality of life of patients. Strict control of blood sugar and blood pressure, including the use of renin–angiotensin–aldosterone system inhibitors, can delay the progression of diabetic nephropathy but cannot prevent it from eventually developing into end-stage renal disease. In recent years, many studies have shown a close relationship between gut microbiota imbalance and the occurrence and development of DN. This review discusses the latest research findings on the correlation between gut microbiota and microbial metabolites in DN, including the manifestations of the gut microbiota and microbial metabolites in DN patients, the application of the gut microbiota and microbial metabolites in the diagnosis of DN, their role in disease progression, and so on, to elucidate the role of the gut microbiota and microbial metabolites in the occurrence and prevention of DN and provide a theoretical basis and methods for clinical diagnosis and treatment.
... Another probiotic strain, Lactobacillus gasseri BNR17, can reduce obesity by upregulating the expression of genes related to fatty acid oxidation-related genes [47]. Probiotics containing Streptococcus thermophilus increase the release of SCFAs which stimulate the release of GLP-1 from intestinal cells, resulting in reduced food intake and improved glucose tolerance [105]. ...
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Functional foods with probiotics are safe and effective dietary supplements to improve overweight and obesity. Thus, altering the intestinal microflora may be an effective approach for controlling or preventing obesity. This review aims to summarize the experimental method used to study probiotics and obesity, and recent advances in probiotics against obesity. In particular, we focused on studies (in vitro and in vivo) that used probiotics to treat obesity and its associated comorbidities. Several in vitro and in vivo (animal and human clinical) studies conducted with different bacterial species/strains have reported that probiotics promote anti-obesity effects by suppressing the differentiation of pre-adipocytes through immune cell activation, maintaining the Th1/Th2 cytokine balance, altering the intestinal microbiota composition, reducing the lipid profile, and regulating energy metabolism. Most studies on probiotics and obesity have shown that probiotics are responsible for a notable reduction in weight gain and body mass index. It also increases the levels of anti-inflammatory adipokines and decreases those of pro-inflammatory adipokines in the blood, which are responsible for the regulation of glucose and fatty acid breakdown. Furthermore, probiotics effectively increase insulin sensitivity and decrease systemic inflammation. Taken together, the intestinal microbiota profile found in overweight individuals can be modified by probiotic supplementation which can create a promising environment for weight loss along enhancing levels of adiponectin and decreasing leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, and transforming growth factor (TGF)-β on human health.
... The current findings indicated an increase in the abundance of these bacteria in GD patients. Heat-killed Streptococcus thermophilus reinforces the immunity of the intestinal mucosa, inhibits inflammation, and improves glycaemic parameters in diabetic rats [26]. Conversely, intraperitoneal injection of Streptococcus dysgalactiae subsp. ...
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Aim To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. Methods A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. Results (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). Conclusions Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. Trial registration The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455).
... As for the studies conducted to date addressing the effects of parabiotics in glycaemic control, reductions in blood glucose and insulin levels have also been described in a recent study carried out in Zucker fatty diabetic rats that were treated with a different parabiotic (heat-killed Streptococcus thermophilus) and for a longer experimental period (12 weeks) 44 . Thus, the results obtained in the current research along with those reported by other authors, suggest that the viability of probiotic bacteria is not essential to preventing glycaemic impairments at least in rodent experimental models. ...
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Insulin resistance and type 2 diabetes are obesity-related health alterations, featuring an ever-increasing prevalence. Besides inadequate feeding patterns, gut microbiota alterations stand out as potential contributors to these metabolic disturbances. The aim of this study was to investigate whether the administration of a probiotic (Lactobacillus rhamnosus GG) effectively prevents diet-induced insulin resistance in rats and to compare these potential effects with those exerted by its heat-inactivated parabiotic. For this purpose, 34 male Wistar rats were fed a standard or a high-fat high-fructose diet, alone or supplemented with viable or heat-inactivated Lactobacillus rhamnosus GG. The body and white adipose tissue weight increases, induced by the obesogenic diet, were prevented by probiotic and parabiotic administration. The trend towards higher basal glucose levels and significantly higher serum insulin concentration observed in the non-treated animals fed with the obesogenic diet were effectively reverted by both treatments. Similar results were also found for serum adiponectin and leptin, whose levels were brought back by the probiotic and parabiotic administration to values similar to those of the control animals. Noteworthily, parabiotic administration significantly reduced skeletal muscle triglyceride content and activated CPT-1b compared to the non-treated animals. Finally, both treatments enhanced Akt and AS160 phosphorylation in the skeletal muscle compared to the non-treated animals; however, only parabiotic administration increased GLUT-4 protein expression in this tissue. These results suggest that heat-inactivated Lactobacillus rhamnosus GG seem to be more effective than its probiotic of origin in preventing high-fat high-fructose diet-induced insulin resistance in rats.
... The anti-diabetic properties of L. paracasei strain NL41 were found to prevent T2DM in rats through a decrease in IR and oxidative stress and to protect beta-cell function by inhibiting beta-cell loss and alpha-cell expansion (Zeng et al. 2019). The effect of heat-killed Streptococcus thermophilus on the Zucker diabetic fatty (ZDF) rat model of T2DM and its possible mechanisms of action suggest that probiotic intake lowers FBG levels and improves glucose intolerance and total cholesterol (improvement in glycemic parameters) (Gao et al. 2019). The outcomes of a ZDF rat model study showed amelioration of glucose homeostasis and protection from T2DM (Cabello-Olmo et al. 2019). ...
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Type 2 diabetes mellitus (T2DM) is a serious endocrine and metabolic disease that is highly prevalent and causes high mortality and morbidity rates worldwide. This review aims to focus on the potential of probiotics in the management of T2DM and its complications and to summarise the various mechanisms of action of probiotics with respect to T2DM. In this review, experimental studies conducted between 2016 and 2022 were explored. The possible mechanisms of action are based on their ability to modulate the gut microbiota, boost the production of short-chain fatty acids (SCFAs) and glucagon-like peptides, inhibit α-glucosidase, elevate sirtuin 1 (SIRT1) levels while reducing fetuin-A levels, and regulate the level of inflammatory cytokines. This review recommends carrying out further studies, especially human trials, to provide robust evidence-based knowledge on the use of probiotics for the treatment of T2DM. • IMPACT STATEMENT • T2DM is prevalent worldwide causing high rates of morbidity and mortality. • Gut microbiota play a significant role in the pathogenesis of T2DM. • Probiotics can be used as possible therapeutic tools for the management of T2DM. • The possible mechanisms of action of probiotics include modulation of the gut microbiota, production of SCFAs and glucagon-like peptides, inhibition of α-glucosidase, raising SIRT1, reducing fetuin-A levels, and regulating the level of inflammatory cytokines.
... Hence, this bacterium is regularly consumed as a part of dairy products worldwide. In vitro and in vivo studies revealed that several strains of S. thermophilus, even non-living, displayed anti-inflammatory properties [17,19,29]. However, there is little evidence that its surface proteins could contribute to the modulation of inflammation. ...
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Streptococcus thermophilus, a food grade bacterium, is extensively used in the manufacture of fermented products such as yogurt and cheeses. It has been shown that S. thermophilus strains exhibited varying anti-inflammatory activities in vitro. Our previous study displayed that this activity could be partially due to peptide(s) generated by trypsin hydrolysis of the surface proteins of S. thermophilus LMD-9. Surface protease PrtS could be the source of these peptides during gastrointestinal digestion. Therefore, peptide hydrolysates were obtained by shaving two phenotypically distinct strains of S. thermophilus (LMD-9 PrtS+ and CNRZ-21N PrtS−) with pepsin, a gastric protease, followed or not by trypsinolysis. The peptide hydrolysates of both strains exhibited anti-inflammatory action through the modulation of pro-inflammatory mediators in LPS-stimulated THP-1 macrophages (COX-2, Pro-IL-1β, IL-1β, and IL-8) and LPS-stimulated HT-29 cells (IL-8). Therefore, peptides released from either PrtS+ or PrtS− strains in the gastrointestinal tract during digestion of a product containing this bacterium may display anti-inflammatory effects and reduce the risk of inflammation-related chronic diseases.
... Mouse HFD STZ-induced diabetes [77] Heat-inactivated Streptococcus thermophilus Rat HFD ZDF diabetes [84] Bacillus licheniformis Zhengchangsheng ® Mouse HFD-induced obesity [87] Probioglu TM Rat STZ-induced diabetes [89] Bacillus toyonensis SAU-19 Mouse HFD ZDF-induced diabetes [90] Lactobacillus ↑ IL-10 ...
... Heat-inactivated Streptococcus thermophilus Rat HFD ZDF-induced diabetes [84] Lactobacillus casei LC89 Mouse STZ-induced diabetes [91] Bifidobacterium animalis 01 Rat High-fat chow diet STZ-induced diabetes [81] Lactobacillus plantarum CCFM0236 Mouse HFD STZ-induced diabetes [78] T2D: type 2 diabetes; FPG: fasting plasma glucose; HbA1c: glycohemoglobin; HOMA-IR: homeostasis model assessment-estimated insulin resistance; HOMA-B: index reflecting pancreatic beta-cell function; ISI: insulin sensitivity index; QUICKI: quantitative insulin sensitivity check index; OGTT: oral glucose tolerance test; IL-6: interleukin-6; IL-10: interleukin 10; IL-1β: interleukin 1 beta; TNFα: tumour necrosis factor alpha; ZDF: Zucker diabetic fatty; HFD: high-fat diet; STZ: streptozotocin; Db/db: genetically mutated model for type 2 diabetes with improper leptin receptor function; AD: Alzheimer's disease; ↓: decrease; ↑: increase. ...
... Oral intake of probiotic preparations of the strains Lactobacillus casei and Bifidobacterium bifidum (alone or both simultaneously) reduced the incidence of hyperglycaemia (increased blood glucose concentration) and dyslipidaemia (imbalance of blood lipid concentration) in rats with induced diabetes [79]. Similar antidiabetic effects in rats were obtained by administration of probiotic strains Lactobacillus plantarum TN627 [80], Bifidobacterium animalis 01 [81], Lactobacillus paracasei HII01 [82], 9 strains of Lactobacillus rhamnosus, Bifidobacterium adolescentis and Bifidobacterium bifidum [77], Lactobacillus rhamnosus BSL and R23 [83], heat-inactivated Streptococcus thermophilus [84], Lactiplantibacillus plantarum IMC 510 [85] and Lactobacillus fermentum RS-2 [86]. In the latter case, in addition to reduced glucose levels in fasting state, a low oxidative stress was observed [86]. ...
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The maintenance of a healthy status depends on the coexistence between the host organism and the microbiota. Early studies have already focused on the nutritional properties of probiotics, which may also contribute to the structural changes in the gut microbiota, thereby affecting host metabolism and homeostasis. Maintaining homeostasis in the body is therefore crucial and is reflected at all levels, including that of glucose, a simple sugar molecule that is an essential fuel for normal cellular function. Despite numerous clinical studies that have shown the effect of various probiotics on glucose and its homeostasis, knowledge about the exact function of their mechanism is still scarce. The aim of our review was to select in vivo and in vitro studies in English published in the last eleven years dealing with the effects of probiotics on glucose metabolism and its homeostasis. In this context, diverse probiotic effects at different organ levels were highlighted, summarizing their potential mechanisms to influence glucose metabolism and its homeostasis. Variations in results due to different methodological approaches were discussed, as well as limitations, especially in in vivo studies. Further studies on the interactions between probiotics, host microorganisms and their immunity are needed.
... Thereby, LAB isolated from kimchi showed an anti-inflammatory effect on acid-induced acute colitis in model mice [12]. Gao et al. (2019) showed that the heat-killed S. thermophilus decreased the inflammatory markers such as LPS, IL-6 and TNF-α and increased the anti-inflammatory interleukin IL-10 in Zucker diabetic fatty rats [34]. Junjua et al. 2016 reported in vitro an anti-inflammatory activity of various live S. thermophilus strains [28]. ...
... Thereby, LAB isolated from kimchi showed an anti-inflammatory effect on acid-induced acute colitis in model mice [12]. Gao et al. (2019) showed that the heat-killed S. thermophilus decreased the inflammatory markers such as LPS, IL-6 and TNF-α and increased the anti-inflammatory interleukin IL-10 in Zucker diabetic fatty rats [34]. Junjua et al. 2016 reported in vitro an anti-inflammatory activity of various live S. thermophilus strains [28]. ...
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Streptococcus thermophilus, a lactic acid bacterium widely used in the dairy industry, is consumed regularly by a significant proportion of the population. Some strains show in vitro anti-inflammatory activity which is not fully understood. We hypothesized that peptides released from the surface proteins of this bacterium during digestion could be implied in this activity. Consequently, we prepared a peptide hydrolysate by shaving and hydrolysis of surface proteins using trypsin, and the origin of peptides was checked by liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis. Most of the identified peptides originated from bacterial cell surface proteins. The anti-inflammatory activity of peptide hydrolysate was investigated under inflammatory conditions in two cell models. Peptide hydrolysate significantly decreased secretion of pro-inflammatory cytokine IL-8 in lipopolysaccharide (LPS)-stimulated human colon epithelial HT-29 cells. It also reduced the production of pro-inflammatory cytokines IL-8, IL-1β and the protein expression levels of Pro-IL-1β and COX-2 in LPS-stimulated THP-1 macrophages. The results showed that peptides released from bacterial surface proteins by a pancreatic protease could therefore participate in an anti-inflammatory activity of S. thermophilus LMD-9 and could prevent low-grade inflammation.
... Many commercial probiotic products available on the market all over the world contain STH [26], although its ability to survive the stomach environment can be questionable for a probiotic [25,27]. The presence of STH in fermented products has been linked to various beneficial effects on human health, including alleviation of lactose intolerance [28], inhibition of pathogens [29], prevention of diarrhea [30,31], modulation of inflammation and cytokine production [32][33][34][35][36], reduction of uremia [37], decrease of total cholesterol and low-density lipoprotein cholesterol [38,39], prevention of the development of insulin resistance and improvement of glycemic parameters [40,41], reduced risk of developing certain cancers [42][43][44], prevention or treatment of inflammatory gut diseases [14,[45][46][47] and maintain gut homeostasis [48]. Although most of the bacterial factors and mechanisms behind these beneficial effects remain unknown, some, however, are being elucidated. ...
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Background Streptococcus thermophilus is a Gram-positive bacterium widely used as starter in the dairy industry as well as in many traditional fermented products. In addition to its technological importance, it has also gained interest in recent years as beneficial bacterium due to human health-promoting functionalities. The objective of this study was to inventory the main health-promoting properties of S. thermophilus and to study their intra-species diversity at the genomic and genetic level within a collection of representative strains. Results In this study various health-related functions were analyzed at the genome level from 79 genome sequences of strains isolated over a long time period from diverse products and different geographic locations. While some functions are widely conserved among isolates (e.g., degradation of lactose, folate production) suggesting their central physiological and ecological role for the species, others including the tagatose-6-phosphate pathway involved in the catabolism of galactose, and the production of bioactive peptides and gamma-aminobutyric acid are strain-specific. Most of these strain-specific health-promoting properties seems to have been acquired via horizontal gene transfer events. The genetic basis for the phenotypic diversity between strains for some health related traits have also been investigated. For instance, substitutions in the galK promoter region correlate with the ability of some strains to catabolize galactose via the Leloir pathway. Finally, the low occurrence in S. thermophilus genomes of genes coding for biogenic amine production and antibiotic resistance is also a contributing factor to its safety status. Conclusions The natural intra-species diversity of S. thermophilus , therefore, represents an interesting source for innovation in the field of fermented products enriched for healthy components that can be exploited to improve human health. A better knowledge of the health-promoting properties and their genomic and genetic diversity within the species may facilitate the selection and application of strains for specific biotechnological and human health-promoting purpose. Moreover, by pointing out that a substantial part of its functional potential still defies us, our work opens the way to uncover additional health-related functions through the intra-species diversity exploration of S. thermophilus by comparative genomics approaches.
... Streptococcus and Granulicatella were observed to be related to glycosylation process (66). Moreover, Streptococcus can improve glycemic parameters in T2D mice (67) and has been used as probiotics to help prevent insulin resistance (68). Also, Paraprevotella is related to glucose tolerance, which shows the higher Paraprevotella, the worse in tolerance (69). ...
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White kidney beans contain α-amylase inhibitors that can be used in diet for weight reduction. In this study, we investigated the potential of white kidney bean (phaseolus vulgaris L.) extract enriched in α-amylase inhibitor as a food additive in yogurt to regulate blood glucose in hyperglycemic animals. Five groups of C57BL/6J mice were fed for 8 weeks with standard chow diets, high-fat diets (HFD), or high-fat diets with supplement of α-amylase inhibitor in white kidney beans (P. vulgaris extract, PVE), yogurt (Y), and PVE added yogurt (YPVE), respectively. The HFD weakened glucose tolerance and caused insulin resistance in mice, and changed the characteristics of intestinal flora. The intervention of Y, PVE, and YPVE decreased blood glucose, insulin, hyperlipidemia, and inflammatory cytokine levels in mice fed with HFD. Moreover, the YPVE could regulate the components of host intestinal microbiota toward a healthy pattern, significantly increased the metabolic-related flora Corynebacterium, Granulicatella, and Streptococcus, while it decreased Paraprevotella and Allobaculum. Thus, YPVE markedly increased functions of “Amino Acid Metabolism,” “Energy Metabolism,” “Nucleotide Metabolism,” and declined functions of “Glycan Biosynthesis and Metabolism.” Consequently, YPVE could be developed as a new functional food because of its beneficial prebiotic properties in the metabolic syndrome.