Article

Probiotics and immunosenescence: Cheese as a carrier

Authors:
  • Faculty of Medicine, University of Turku
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Abstract

Oral intake of specific probiotics has been reported to enhance the immunity of the elderly. Earlier studies have used milk or yoghurt as a probiotic carrier. We chose a commercial probiotic cheese to evaluate its potential as a probiotic food. Thirty-one healthy elderly volunteers (21 female, 10 male) aged from 72 to 103 (median 86) consumed a commercial probiotic cheese containing approximately 10(9) CFU day(-1) of Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM. The 4-week probiotic intervention was preceded by a 2-week consumption of probiotic-free cheese (run-in) and followed by a 4-week wash-out period with the same control cheese. The cytotoxicity of peripheral blood mononuclear cells (PBMCs), the relative numbers of natural killer (NK) and NKT cells in the total PBMCs, and phagocytic activity were assessed. Consumption of the probiotic cheese significantly increased the cytotoxicity of NK cells. A significant increase in phagocytosis was observed for both the control and the probiotic cheese. Cheese was found to be an effective carrier for the study of probiotics, and daily consumption of the probiotic enhanced parameters of innate immunity in elderly volunteers. It remains to be determined whether this enhancement correlates with a beneficial effect on the health of the elderly population.

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... The gut microbiota appears to play role in chronic inflammatory disease, through several mechanisms. Colonic microbiota could stimulate infiltration of macrophages in the adipose tissue by providing inflammatory stimuli such as Lipopolysaccarides (LPS) and enhancing energy intake from the food that leads to adipocyte hypertrophy (25)(26)(27) . ...
... Although the gut flora contributes to a healthy environment, acute and chronic mucosal inflammation can arise as a result of both commensal and pathogenic bacteria that influence the innate and adaptive immune-systems. Intestinal microbes can alter host defense mechanisms, leading to the activation of cytokines and the stimulation of adaptive T-cell and B-cell response (26)(27)(28)(29)(30)(31) . ...
Article
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The tear film consists of a set of heterogeneous substances (lipids, proteins, mucin and water) combined in order to form a highly organic tropism structure specialized in the defense of the ocular surface. Dry Eye Disease (DED) is characterized by discomfort, visual disturbance, constant irritation, foreign body sensation, and blurred vision. We evaluate in this preliminary report the effect of supplementation with symbiotic Maxiflor on tear film in DED patients. We recruited 40 patients (27 females and 13 males, age 51.5 +/- 11. 1) showing signs of discomfort and / or dry eyes (burning, foreign body sensation, dryness or itching). Following the run-in period subjects were randomized in two groups: group A (N degrees 20 subjects) and group B (N degrees 20 subjects). Group A (control) treated only with substitute tear and group B treated with substitute tear + mixture (symbiotic). The data obtained in the two study groups A and B were, respectively the following: Schirmer 10.1 +/- 0.2 vs 12.7 +/- 0.4 (p < 0.001); Schirmer II 3.6 +/- 0.1 VS 4.6 +/- 0.2 (p<0.001); Fluorescein in break-up time (TF BUT) 4.1 +/- 0.3 vs 6.5 +/- 0.2 (p<0.001). Culture test showed initial bacterial growth in 18 out of 40 samples tested in group "A" (control), corresponding to 45.0%; whereas bacterial culture was found positive after treatment in 14 out of 40 tests, equal to 35.0%, in group "B" (symbiotic). A reduction of 16 to 12 strains of aerobic and anaerobic isolates from 10 to 6 has been found. The present study shows that the administration of Bifidobacteria and Lactobacillus may represent a successful treatment in ameliorating DED.
... As we grow older, epithelial barriers of the skin, lung and gastrointestinal tract degrade enabling increased invasion of delicate mucosal tissues by pathogens [6]. A significant reduction in humoral response (immune response that is mediated by B cells) is therefore observed following vaccination or infections [7]. The immune system itself may be divided into various parts: the innate part, consisting of cytokines, neutrophils, macrophages, natural killer (NK) cells and dendritic cells and the adaptive part, represented by T and B-cells [8]. ...
... Effect of probiotics on gut microbiota in elderly humans -epidemiological evidence improved of phagocytic ability in older volunteers (>70 years old)[7]. This supports the findings noted by Gill et al. who reported elevated INF-␣, lymphocyte counts, circulating counts of T cells (CD4 + , CD25 + cells) and increased tumoricidal activity of NK cells in elderly subjects consuming milk containing Bifidobacterium lactis HN019 for 9 weeks ...
Article
The global population is becoming increasingly older presenting medical and economic challenges to society. One factor associated with the aging process is immunosenescence, which may be defined as the decline in immunity with age, and represents a potential causative factor for many age related illnesses. The profile of the gut microbiota is also known to alter with aging and these changes have been linked the declines in the immunity observed in immunosenescence. For example, above the age of 60 years populations of bifidobacteria have been observed to decrease markedly, leading to a reduction in the inhibition of the growth of some pathogens and potentially an increase in the susceptibility to infections. As such, an interest exists in attempting to reverse their decline in elderly individuals, through the use of both probiotics and prebiotics. Both approaches have shown to be encouraging in altering microbiota profiles beneficially and in reducing immunosenescence by reducing the colonisation potential of pathogens and counteracting chronic inflammation. The current review will give an overview of the process of immunosenescence and its role in disease, detail how the microbiota are involved in its progression and highlight data suggesting that pre- and probiotics may counteract these age-related events.
... The activity was correlated to production of metabolites such as lactic and acetic acid and that reduced the pH. In the same context, Reis et al. (2012), Ibrahim et al. (2010) explained the activity of Probiotic cell free supernatant by presence of acetic acid, lactic acid, organic acids, hydrogen peroxide, diacetyl, phenols and bacteriocins using GC-Mass. ...
... Subsequently, the immunocompromised patients develop fibroses followed by cirrhosis and end up by HCC. Throughout all these stages several biochemical changes have been noticed including decreasing of albumin, increasing of liver enzymes, liver dysfunction, immune dysfunction, diarrhea, respiration and digestion difficulties (Ibrahim et al., 2010). Due to these dysfunction several other side effects emerge which are related to secondary bacterial infection. ...
... Studies were included if they were written in English and analysed the relationship between inflammageing and gut microbiota either in humans or in animals. The definition of "older adults" age-range varies among authors (Ibrahim et al., 2010;Cleary and Skornyakov, 2017;Eckardt, 2016;Birimoglu Okuyan and Bilgili, 2019). Therefore, to avoid missing our target population of elderly individuals, we also included this as a search term. ...
... Aged individuals who consumed milk containing Bifidobacterium lactis for 6 weeks produced significantly enhanced levels of interferon-alpha upon stimulation of their peripheral blood mononuclear cells in culture (Arunachalam et al., 2000). Likewise, administration of a commercial probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NSFM to healthy elderly volunteers increased the cytotoxicity of their natural killer cells (Ibrahim et al., 2010). However, these intervention studies were not included as part of this systematic review. ...
Article
Ageing is characterized by a low-grade chronic inflammation marked by elevated circulating levels of inflammatory mediators. This chronic inflammation occurring in the absence of obvious infection has been coined as inflammageing and represents a risk factor for morbidity and mortality in the geriatric population. Also, with ageing, important perturbations in the gut microbiota have been underlined and a growing body of literature has implicated age-related gut dysbiosis as contributing to a global inflammatory state in the elderly. Notwithstanding, very little attention has been given to how gut microbiota impact inflammageing. Here, we investigate the available evidence regarding the association between inflammageing and gut microbiota during ageing. PubMed, Web of Science and Scopus were systematically screened, and seven relevant articles in animals or humans were retrieved. The animal studies reported that Parabacteroides, Mucispirillum, Clostridium and Sarcina positively associate with the pro-inflammatory MCP-1 while Akkermansia, Oscillospira, Blautia and Lactobacillus negatively correlate with MCP-1. Furthermore, “aged”-type microbiota were associated with increased levels of IL6, IL-10, Th1, Th2, Treg, TNF-α, TGF-β, p16, SAMHD1, Eotaxin, and RANTES; activation of TLR2, NF-κB and mTOR; and with decreased levels of cyclin E and CDK2. On the other hand, the study on humans demonstrated that bacteria of the phylum Proteobacteria exhibited a positive correlation with IL-6 and IL-8, while Ruminococcus lactaris et rel. portrayed a negative correlation with IL-8. We conclude that changes in “aged”-type gut microbiota are associated with inflammageing.
... Unsurprisingly, the deficiency of some of these micronutrients compromises the proper immune response, increasing susceptibility to infections. Moreover, several other compounds, such as omega 3 fatty acids, specific amino acids, phytochemicals (e.g., resveratrol and astaxanthin), and natural-derived drugs such as rapamycin and metformin, are known to exert antiaging, antiviral, and immunomodulatory effects and maintain a healthy immune system [2,[50][51][52][53]. In particular, polyphenols such as curcumin, flavanols, and resveratrol interact with the gut microbiota where they undergo extensive metabolism to produce small molecules active on transcription factors (Nrf2, PGC1-α, FoXO3, AMPK, Sirt1) involved in several cellular functions, including mitochondrial biogenesis, antioxidant systems, glucose and lipid homeostasis, DNA repair, and immune homeostasis [54][55][56][57]. ...
Article
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Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one of the meaningful aspects of aging. Unsurprisingly, nutraceutical and pharmacological interventions could help maintain an optimal biological response by providing essential bioactive micronutrients required for the development, maintenance, and the expression of the immune response at all stages of life. In this regard, many studies have provided evidence of potential antiaging properties of resveratrol, as well as rapamycin and metformin. Indeed, in vitro and in vivo models have demonstrated for these molecules a number of positive effects associated with healthy aging. The current review focuses on the mechanisms of action of these three important compounds and their suggested use for the clinical treatment of immunosenescence and aging.
... Sufficient administration of probiotics, as live microorganisms, offer various health benefits, including an improved immune system functions, a better rearrangement in the intestinal microflora and an induction of antagonistic/inhibitory effects on the growth of harmful bacteria (Asoudeh-Fard et al., 2017;Ibrahim et al., 2010). Lactobacillus species as the most important probiotic bacteria are compatible with the human gastrointestinal system because of their innate resistance to acid, bile, and interfering enzymes such as pepsin and pepsinogen (Liong & Shah, 2005;Vamanu & Vamanu, 2010). ...
... Another meta-analysis analyzed the preventive effect of probiotics on the occurrence of infection and concluded to an absence of effect on infection occurrence, duration and mortality (Wachholz et al. 2018) in elderly. When PBMC cytotoxicity was assessed in vitro, results were more consistent with a maintenance or increase of these parameters following pro or symbiotic supplementation (Ibrahim et al. 2010;Spaiser et al. 2015). Overall, pro or symbiotics, even if generally proven efficient to limit inflammation or gut leaking in animal models (Morita et al. 2018;Vemuri et al. 2019;Wang et al. 2020), fail to clearly improve immune status in elderly population. ...
Article
Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.
... The activity was correlated to production of metabolites such as lactic and acetic acid and that reduced the pH. In the same context, Reis [41], Ibrahim [42] explained activity of Probiotic cell free supernatant by presence of acetic acid, lactic acid, organic acids, hydrogen peroxide, diacetyl, phenols and bacteriocins using GC-Mass. ...
Article
Full-text available
Abstract- Hepatitis C virus is a major leading cause of Liver pathogenesis. Probiotics showed a natural therapeutic activity against liver disorders. The antiviral and the antibacterial responses to L. acidophilus and Bifidobacteria spp in patients with chronic hepatitis C virus is a recommended study. Patients with chronic hepatitis C were treated with probiotics capsule that contains L. acidophilus and Bifidobacterium spp. They administered one capsule per day for a month before HCV treatment, blood and urine samples were collected before and after the given treatment and they were processed for a quantitative estimation of HCV by PCR, identification of bacteria by VITEK2 system and 16S r RNA gene sequencing assay, moreover, the estimation of antibacterial activity of probiotics, as well as counts of leukocytes, CD3+ T cells and CD56+ natural killer cells. Administration of Probiotics capsule enhanced the treatment response rate to HCV treatments as IFN-α and ribavirin by 25%. It had antibacterial activity against five species of the most common bacterial infections also It increased CD3+ cells counts and CD56+ natural killer cells in chronic HCV patients. Administration of probiotics as a capsule before HCV treatment can act as a supportive supplement with antiviral and antibacterial activities. Index Terms - CD3+; CD56+; Hepatitis C virus; Lactobacillus acidophilus; Bifidobacterium bifidum.
... Aged subjects fed milk containing L. rhamnosus HN001 or B. lactis HN019 for 3-6 weeks exhibited significantly higher phagocytic activity than subjects fed milk without probiotics (Arunachalam et al. 2000;Gill et al. 2001aGill et al. , 2001bGill and Rutherfurd 2001;Sheih et al. 2001). A recent study (Ibrahim et al. 2010) involving elderly subjects (median age 86 years) given probiotic cheese (10 9 colony-forming units [CFU]/day of L. rhamnosus HN001 and L. acidophilus NCFM for 4 weeks) also reported significantly enhanced granulocyte and monocyte phagocytic activity (p < .001) as well as the ex vivo cytotoxicity of natural killer (NK) cells (p = .05). Importantly, subjects with relatively poor preintervention immunity status consistently showed greater improvement in phagocytic cell function than subjects with adequate preintervention immune function (Gill et al. 2001c). ...
Chapter
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The human gastrointestinal tract (GIT) represents the largest body surface area exposed to the external environment. It is continuously challenged by a diverse array of environmental, dietary, and microbial antigens (derived from the enteric flora). In addition to facilitating digestion and allowing absorption of nutrients, the GIT performs a very complex and delicate function of exhibiting tolerance to innocuous environmental antigens and enteric flora, but at the same time mounting an aggressive immune response toward pathogenic organisms. Failure to tightly regulate these responses leads to enhanced susceptibility to infectious diseases and immunoinflammatory disorders. To perform these functions efficiently, the GIT is endowed with the largest immune system in the body.
... (Table 5). [22] No No Before-after X X Costabile, 2017 [23] Yes Yes Crossover X Dong, 2013 [24] Yes Yes Crossover X X Gill, 2001a [25] No No Before-after X X Gill, 2001b [26] No Yes Before-after X Gill, 2001c [27] No Yes Before-after X Gill, 2001d [28] No Yes Before-after X X Ibrahim, 2010 [29] No Yes Before-after X X Lee, 2017 [30] Yes No Parallel group X Makino, 2010 [18] Yes No Parallel group X Maneerat, 2013 [31] Yes Yes Crossover X Miyazawa, 2015 [32] Yes Yes Parallel group X Nyangale, 2015 [33] Yes Yes Crossover X Sheih, 2001 [34] No Yes Before-after X X Takeda, 2006 [35] Yes Yes Crossover X Upadhyaya, 2011 [36] Yes Yes Parallel group X ...
Article
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Immune function declines with advancing age. Probiotic supplementation has been proposed to slow or reverse these age-related changes. The primary objective of this study was to evaluate the effect of probiotic supplementation on cellular innate immune activity in healthy elderly subjects. We hypothesized that probiotic supplementation would enhance immune function. We performed a systematic review and meta-analysis of controlled trials that reported polymorphonuclear cell phagocytic capacity or natural killer (NK) cell tumoricidal activity following short-term probiotic supplementation in the elderly. Effect size was reported as the standardized mean difference (SMD) between probiotic and control groups, where values of 0.2, 0.5, 0.8, and 1.0 corresponded to small, medium, large, and very large effect sizes, respectively. A total of 17 prospective controlled studies (18 comparisons) of 733 subjects were included. Probiotic supplementation duration ranged from 3 to 12 weeks. Probiotic supplementation increased polymorphonuclear phagocytic capacity (SMD = 1.37, 95% confidence interval: 0.86-1.88, P <.001) and NK cell tumoricidal activity (SMD = 0.55, 95% confidence interval: 0.37-0.73, P <.001) relative to controls. In a subgroup analysis of NK cell activity, heterogeneity among studies was not explained by variability in study design or probiotic characteristics. Main limitations of this research were short-term supplementation durations and unclear clinical benefit of the immune changes. In conclusion, short-term probiotic supplementation enhances cellular immune function in healthy elderly adults.
... The gut microbiota plays a critical role in the immune system, and aging has been reported to alter gut bacterial flora composition [35]. Previous studies have reported that some prebiotics and probiotics can alter gut bacterial flora composition and improve immune defects [44,45]. Therefore, to investigate whether intake of L. paracasei KW3110 affected the gut microbiota composition in aged mice, 16-month-old mice were fed a diet with or without L. paracasei KW3110 for 6 months. ...
Article
Age-related chronic inflammation is a major risk factor for the incidence and prevalence of age-related diseases, including infectious and neurodegenerative diseases. We previously reported that a lactic acid bacteria, Lactobacillus paracasei KW3110, activated macrophages and suppressed inflammation in mice and humans. In this study, we investigated whether long-term intake of heat-killed L. paracasei KW3110 modulated age-related inflammation and altered the gut microbiota in physiologically aged mice. Compared with age-matched control mice, fecal analyses of gut microbiota revealed that intake of L. paracasei KW3110 mitigated age-related changes of beneficial bacterial composition, including the Bifidobacteriaceae family. L. paracasei KW3110 intake also mitigated age-related immune defects by reducing the prevalence of interferon-gamma (IFN-γ) -producing inflammatory CD4-positive T cells in the lamina propia of the small intestine, and reduced serum levels of proinflammatory cytokines. Furthermore, L. paracasei KW3110 intake suppressed retinal inflammation by reducing proinflammatory cytokine-producing macrophage, and age-related retinal cell loss. Taken together, these findings suggested that L. paracasei KW3110 mitigated age-related chronic inflammation through modulation of gut microbiota composition and immune system functions in aged mice, and also reduced age-related retinal ganglion cell (RGC) loss. Further studies are needed to evaluate the effect in age-related senescent changes of the retina.
... About 500 probiotic food products have been introduced in the market during the last years (Tripathi & Giri, 2014). Products available commercially are, for example, traditional yoghurt and other fermented dairy products, such as cheese, ice cream, and fermented baby formula (Cruz, Antunes, Sousa, Faria, & Saad, 2009;Gueimonde et al., 2004;Ibrahim et al., 2010;Lourens-Hattingh & Viljoen, 2001;Young, 1998). ...
Article
Edible films and coatings have been extensively studied in recent years due to their unique properties and advantages over more traditional conservation techniques. Edible films and coatings improve shelf life and food quality, by providing a protective barrier against physical and mechanical damage, and by creating a controlled atmosphere and acting as a semipermeable barrier for gases, vapor, and water. Edible films and coatings are produced using naturally derived materials, such as polysaccharides, proteins, and lipids, or a mixture of these materials. These films and coatings also offer the possibility of incorporating different functional ingredients such as nutraceuticals, antioxidants, antimicrobials, flavoring, and coloring agents. Films and coatings are also able to incorporate living microorganisms. In the last decade, several works reported the incorporation of bacteria to confer probiotic or antimicrobial properties to these films and coatings. The incorporation of probiotic bacteria in films and coatings allows them to reach the consumers’ gut in adequate amounts to confer health benefits to the host, thus creating an added value to the food product. Also, other microorganisms, either bacteria or yeast, can be incorporated into edible films in a biocontrol approach to extend the shelf life of food products. The incorporation of yeasts in films and coatings has been suggested primarily for the control of the postharvest disease. This work provides a comprehensive review of the use of edible films and coatings for the incorporation of living microorganisms, aiming at the biopreservation and probiotic ability of food products.
... Conjugated linoleic acid (CLA) is found in cheese, and recent scientific research supports potential roles for CLA isomers in reducing the risk of certain cancers and heart disease, enhancing immune function and regulating body weight/ body fat distribution [132]. Cheese with L. rhamnosus HN001 and L. acidophilus NCFM found to be beneficial in improving the immune response of healthy elderly subjects [133]. Probiotic fresh cheese allows B. bifidum, L. acidophilus and L. paracasei to exert significant immunomodulating effects in the gut [134]. ...
... Conjugated linoleic acid (CLA) is found in cheese, and recent scientific research supports potential roles for CLA isomers in reducing the risk of certain cancers and heart disease, enhancing immune function and regulating body weight/ body fat distribution [132]. Cheese with L. rhamnosus HN001 and L. acidophilus NCFM found to be beneficial in improving the immune response of healthy elderly subjects [133]. Probiotic fresh cheese allows B. bifidum, L. acidophilus and L. paracasei to exert significant immunomodulating effects in the gut [134]. ...
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... NPLN-agar and MRS-LP media have been prepared by the supplementation of lithium chloride and sodium propionate or by the supplementation of lithium chloride, sodium propionate, and l-cysteine. HCl (Ashraf and Shah, 2011;Ibrahim et al., 2010). Neomycin sulfate and nalidixic acid are included as growth inhibitors of Gram-positive and Gram- negative rods, respectively, and also lithium chloride is commonly used as a selective agent in bifidobacterial enumeration (Roy, 2001). ...
Chapter
Probiotic bacteria are increasingly applied in the food industry, such as milk, vegetables, or meat products. According to FAO/WHO (2002) recommendation, to exert their positive effect on the host, they must be ingested in adequate amount, that is, probiotic bacteria should be 10⁶-10⁹CFU/g in the product at the time of ingestion. Moreover, the positive effect on the host is connected with the specific strain of bacteria, not the genus or species. The correct species identification of bacteria is of paramount importance from the technological, ecological, and safety point of view. So far there is no standard method for the identification of probiotics. Therefore, the need to develop fast and efficient methods of probiotic identification in food matrices occurs. The aim of the work is to provide different methods of enumeration and identification of probiotic bacteria in food according to the culture-dependent and culture-independent techniques, such as phenotyping, biochemical, physical, immunological, and molecular biology methods. In particular, the direct identification potential of molecular tools, such as DNA, RNA, and peptide analysis will be highlighted.
... Supplementation of cheeses with probiotic LAB adds value and provides potential health benefits (Gomes et al., 2011;Minervini et al., 2012). Intake of cheese supplemented with probiotic bacteria has been associated with a variety of health-promoting benefits, such as immune system improvement, oral and gut health effects in the elderly, prevention of food allergies, and strengthening of intestinal immunity (Albenzio et al., 2013a;Albenzio et al., 2013b;Hatakka et al., 2007;Ibrahim et al., 2010;Lollo et al., 2012;McFarland, 2000;Medici et al., 2004;Modzelewska-Kapituła et al., 2010). In a previous study, we isolated probiotics from fecal samples of healthy Korean neonates. ...
Article
The effect of addition of the probiotic Bifidobacterium longum KACC 91563 on the chemical and sensory properties of Kwark cheese produced using CHN-11 as a cheese starter were investigated. The addition of B. longum KACC 91563 to Kwark cheese did not change the composition or pH value of the cheese, compared with control. B. longum KACC 91563 survived at a level of 7.58 Log CFU/g and did not have any negative effect on survival of the cheese starter. A sensory panel commented that the addition of B. longum KACC 91563 made Kwark cheese more desirable to consumers, and that the probiotic supplementation had no effect on perceived taste. Thus, B. longum KACC 91563 can be used for inclusion of probiotic bacteria in cheese.
... Bifidobacterium lactis HN019 enhanced phagocytic activity and number of NK cells in elderly subjects [51,58,59]. A probiotic cheese containing Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NSFM increased the cytotoxicity of NK cells in elderly volunteers [60]. Administration of yogurt containing the probiotic strain Lactobacillus casei DN-114001 to elderly people reduced the length of winter infections compared to the control group [61]. ...
Article
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Age-related degeneration gives rise to a number of pathologies, many of them associated with imbalances of the microbiota and the gut-associated immune system. Thus, the intestine is considered a key target organ to improve the quality of life in senescence. Gut microbiota can have a powerful impact in the deterioration linked to aging by its nutritional and immunomodulatory activity. Reduced numbers of beneficial species and low microbial biodiversity in the elderly have been linked with pathogenesis of many diseases. A healthy lifestyle with an elderly customized diet including probiotics can contribute to reducing the chronic proinflammatory status and other age-related pathologies. Beneficial effects of probiotic lactic acid bacteria and bifidobacteria to alleviate some of these disorders based on their immunomodulatory properties as well as their capacity to produce bioactive metabolites from dietary phytoestrogens are summarized. On one hand, the preservation of gut barrier integrity and an increased ability to fight infections are the main reported immune benefits of probiotics. On the other hand, the intake of a diet rich in phytoestrogens along with the presence of selected probiotic bacteria may lead to the production of equol, enterolignans, and urolithins, which are considered protective against chronic diseases related to aging.
... These autochthonous bacteria interact with the diet and the host, contributing to protection against intestinal pathogens through colonization resistance and providing nutritional and colonic health benefits via their metabolic activities (Guarner and Malagelada, 2003;Sleator and Hill, 2008;Sleator, 2010). It has become clear that these bacteria also interact with the host's immune system and are essential for the maturation and homeostasis of a healthy immune system (Isolauri et al., 2001;Mishra et al., 2008;Ibrahim et al., 2010). Recognition of the importance of the intestinal microbiota to health has led to increasing interest in manipulating the composition and/or activity of the microbiota to improve both human and animal health (Corr et al., 2007;Raoult, 2009;Allen et al., 2010). ...
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Investigation on the microbial safety and probiotic potentials of different yoghurt brands sold in Owerri, Imo State Nigeria, was carried out using standard microbiological procedures. Ten each, of five different brands of commercially available yoghurt packaged in plastic containers were purchased from the street vendors and shopping malls in Owerri metropolis. The mean total count of samples on Brain Heart Infusion (BHI) and De Mann Rogosa Sharpe (MRS) agar media ranged from 2.0×10 7 to 6.0×10 8 and 1.0×10 8 to 5.4 × 10 8 cfu/ml respectively. The yoghurt isolates were identified as Streptococcus and Lactobacillus species; these isolates were resistant to commonly used antibiotics and inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa from clinical samples. No viable growth of isolates was observed in simulated gastric fluid of pH 1.5 to 2.5. Slight decrease in viable count of Lactobacillus spp. from 4.0×10 7 to 3.0×10 7 cfu/ml and Streptococcus spp. from 3.0×10 8 to 2.0×10 8 cfu/ml was observed in bile of pH 8.28 to 8.30. The isolates were recovered from faecal samples two weeks after ingestion with mean count ranging from no growth (zero) to 5.8×10 8 cfu/ml on MRS agar media. The isolates were found to exhibit some probiotic potentials and no pathogen was isolated from samples. It is recommended that strains of microorganisms that can deliver full probiotic potentials to consumers be used in commercial yoghurt production.
... Effect of other probiotics than HN019 studies have also been investigated on NK cell activity. A combination of L. rhamnosus HN001 and L. acidophilus NCFM resulted in a significantly increased cytotoxicity of the NK cells [39]. In contrast, B. longum BB536 intake for 12 weeks had no effect on NK cell activity in elderly patients fed by enteral tube feeding [40] and L. gasseri TMC0356 supplementation for 4 weeks had no significant impact on NK cell counts or NK cell activity [41]. ...
Article
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Elderly people have increased susceptibility to infections and cancer that are associated with decline in cellular immune function. The objective of this work was to determine the efficacy of Bifidobacterium (B.) animalis ssp. lactis HN019 (HN019) supplementation on cellular immune activity in healthy elderly subjects. We conducted a systematic review of Medline and Embase for controlled trials that reported polymorphonuclear (PMN) cell phagocytic capacity or natural killer (NK) cell tumoricidal activity following B. lactis HN019 consumption in the elderly. A random effects meta-analysis was performed with standardized mean difference (SMD) and 95% confidence interval between probiotic and control groups for each outcome. A total of four clinical trials were included in this analysis. B. lactis HN019 supplementation was highly efficacious in increasing PMN phagocytic capacity with an SMD of 0.74 (95% confidence interval: 0.38 to 1.11, p < 0.001) and moderately efficacious in increasing NK cell tumoricidal activity with an SMD of 0.43 (95% confidence interval: 0.08 to 0.78, p = 0.02). The main limitations of this research were the small number of included studies, short-term follow-up, and assessment of a single probiotic strain. In conclusion, daily consumption of B. lactis HN019 enhances NK cell and PMN function in healthy elderly adults.
... It is also important for maintaining gastrointestinal health. As a naturally occurring probiotic, Bifidobacteria and Lactobacilli can modify the metabolic activities in the body by modulating immune system [1], producing antimicrobial agents such as hydrogen peroxide, antimicrobial peptides (bacteriocins), and organic acids such as acetic and lactic acids [2]. When used in adequate amounts in diet, they can synthesis vitamins (such as K and B), stabilize barrier functions and enhance the calcium and other mineral absorption on the gut. ...
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Background In this study, in vitro prebiotic effects of Jerusalem artichoke poly-fructans on the survivability and activity of Bifidobacterium bifidum, Escherichia coli were investigated and compared with HP-Inulin (a high molecular-weight fraction of chicory-derived inulin). Objectives The prebiotic potential of poly-fructans extracted from native Jerusalem artichoke tubers on the survivability of B. bifidum and E. coli was evaluated in this study. Methods In this experimental study, 24 treatments divided to 2 groups (Extracted poly-fructose from Jerusalem artichoke tubers and standard inulin) randomly. The turbidity and pH variations during 48 hours incubation were determined using final concentrations of each group (0.5%, 1%, 2% and 3% (w/v)). The data were analyzed by MINITAB 14 and MSTATC statistical software, one way ANOVA and Duncan’s test. Results This study suggests that Jerusalem artichoke tuber fructooligosaccharides (JA-Fr) had the potential to be used as a prebiotic component. The growth of B. bifidum improved significantly in the presence of Jerusalem artichoke fructans compared to the control. There was no significant differences (P < 0.05) in Bifidobacterium population in different concentrations of Jerusalem artichoke poly-fructans, but the population was significantly higher than the count in the presence of HP-inulin. The pH decreased in both media during 48 hours incubation time. Specific rate of growth and doubling time determined for E. coli demonstrated that the efficacy of various carbon sources in stimulating bacterial growth were influenced by the concentration and DP (degree of polymerization) of fructan chains in the media. Conclusions Jerusalem artichoke fructooligosaccharides can provide the greater stability of probiotics and acid production, so it can be considered as a potential source of high-yielding oligosaccharide for commercial prebiotic production to develop food industry and improve host health.
... The activity was correlated to production of metabolites such as lactic and acetic acid and that reduced the pH. In the same context, Reis [41], Ibrahim [42] explained activity of Probiotic cell free supernatant by presence of acetic acid, lactic acid, organic acids, hydrogen peroxide, diacetyl, phenols and bacteriocins using GC-Mass. ...
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Hepatitis C virus is a major leading cause of Liver pathogenesis. Probiotics showed a natural therapeutic activity against liver disorders. The antiviral and the antibacterial responses to L. acidophilus and Bifidobacteria spp in patients with chronic hepatitis C virus is a recommended study. Patients with chronic hepatitis C were treated with probiotics capsule that contains L. acidophilus and Bifidobacterium spp. They administered one capsule per day for a month before HCV treatment, blood and urine samples were collected before and after the given treatment and they were processed for a quantitative estimation of HCV by PCR, identification of bacteria by VITEK2 system and 16S r RNA gene sequencing assay, moreover, the estimation of antibacterial activity of probiotics, as well as counts of leukocytes, CD3 + T cells and CD56 + natural killer cells. Administration of Probiotics capsule enhanced the treatment response rate to HCV treatments as IFN-α and ribavirin by 25%. It had antibacterial activity against five species of the most common bacterial infections also It increased CD3 + cells counts and CD56 + natural killer cells in chronic HCV patients. Administration of probiotics as a capsule before HCV treatment can act as a supportive supplement with antiviral and antibacterial activities.
... Production of specific and/or nonspecific metabolites, like organic acids, diacetyl or bacteriocins, strengthens its antimicrobial effect and helps to prevent bacterial infection. Some research reported on immunomodulatory and tumour-suppressing activity of the NCFM strain [4][5][6]. The ability to strengthen the human immune system was confirmed by Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies [7]. ...
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A strain Lactobacillus acidophilus NCFM Howaru Dophilus (NCFM strain) is a probiotic bacterium with positive health effects proven by extensive research. This work deals with examination of media composition and CO2 concentration effects on the growth and metabolism of Lactobacillus strains. Growth rate (Gr) of NCFM strain in non-supplemented de Man-Rogosa-Sharpe (MRS) broth was 0.348 log CFU·ml⁻¹·h⁻¹, lactic acid production rate (rLA) was 2.07 g·l⁻¹·h⁻¹ and the concentration of produced lactic acid (ΔcLA) reached 12.5 g·l⁻¹. Activity of NCFM strain in milk was significantly lower (Gr = 0.297 log CFU·ml⁻¹·h⁻¹, rLA = 0.16 g·l⁻¹·h⁻¹, ΔcLA = 12.1 g·l⁻¹). Depending on the added substrate, Gr of NCFM strain was 0.295-0.398 log CFU·ml⁻¹·h⁻¹ and 0.260-0.341 log CFU·ml⁻¹·h⁻¹, and the yield of lactic acid ΔcLA was 1.12-14.39 g·l⁻¹ and 1.13-11.57 g·l⁻¹, in MRS broth and milk respectively. Results showed that the most significant stimulation was achieved in medium containing tryptone and the growth limiting factors were mainly free amino acids.
... Based on recent evidence, fermented foods can improve some clinical features including inflammatory biomarkers, including CRP, IL-6, TNF-a [3,45], and play a role in anti-inflammatory processes. However, in some studies it was observed that fermented foods increase some inflammatory markers [33]. As there is inconsistency in results of previous publications, this study aimed to determine the effect of fermented foods on inflammation using randomized clinical trials. ...
Article
Objective: The effect of fermented foods consumption on inflammation has been investigated in several studies, but findings are inconsistent. Therefore we conducted a meta-analysis to examine the effect of fermented foods on inflammatory biomarkers including C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the general adult population. Design: systematic review and meta-analysis. Methods: In this systematic review and meta-analysis, randomized controlled trials in the general adult population comparing fermented foods with a control product were searched from two literature databases (PubMed and Scopus) up to June 4, 2019. Trials with mean difference (MD) of 95% confidence interval (CI) were pooled using random effect model. Heterogeneity was assessed using Cochran's Q and I2 tests. Subgroup analysis was applied to define possible sources of heterogeneity. Results: The search strategy identified 3293 documents. Overall, 26 publications with 1461 people met the inclusion criteria. Our results indicated that intake of fermented foods could reduce serum TNF-α levels ((WMD = -8.26, 95% CI: -14.61, -1.91, p = 0.01; I2 = 99.9%, p < 0.001)). However, no change was observed in serum levels of CRP ((WMD = -0.21, 95% CI: -0.47, 0.05, p = 0.11), I2 = 93.8%, p < 0.001) and IL-6 ((WMD = 0.31, 95% CI:-3.79, 4.43, p = 0.88), I2 = 99.3%, p < 0.001). Conclusion: Our findings showed that intake of fermented foods did not improve serum CRP and IL-6. We observed a reduction in pooled effect of TNF-α following intake of fermented foods.
... 94,S35 The main effects were a slight increase in gut comfort and reduction in constipation, 95 but not always. S36 A few studies reported slight positive effects on increased innate immunity (increased cytotoxicity of NK cells 96 and improvement cytokine profile 97 ). Taken together, the overall small effects observed or the inconsistency of the results observed in health parameters measured in the elderly population can lie on the large heterogeneity of this population in terms of health status, dependency (frail concept 9 ), and life habits (community dwellers vs. residential care), all these 'basal' parameters affecting the response of the host to the probiotic supplementation and finally the validity of parameters used to evaluate immune or health state. ...
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Evidence suggests that gut microbiota composition and diversity can be a determinant of skeletal muscle metabolism and functionality. This is true in catabolic (sarcopenia and cachexia) or anabolic (exercise or in athletes) situations. As gut microbiota is known to be causal in the development and worsening of metabolic dysregulation phenotypes such as obesity or insulin resistance, it can regulate, at least partially, skeletal muscle mass and function. Skeletal muscles are physiologically far from the gut. Signals generated by the gut due to its interaction with the gut microbiome (microbial metabolites, gut peptides, lipopolysaccharides, and interleukins) constitute links between gut microbiota activity and skeletal muscle and regulate muscle functionality via modulation of systemic/tissue inflammation as well as insulin sensitivity. The probiotics able to limit sarcopenia and cachexia or promote health performances in rodents are mainly lactic acid bacteria and bifidobacteria. In humans, the same bacteria have been tested, but the scarcity of the studies, the variability of the populations, and the difficulty to measure accurately and with high reproducibility muscle mass and function have not allowed to highlight specific strains able to optimize muscle mass and function. Further studies are required on more defined population, in order to design personalized nutrition. For elderly, testing the efficiency of probiotics according to the degree of frailty, nutritional state, or degree of sarcopenia before supplementation is essential. For exercise, selection of probiotics capable to be efficient in recreational and/or elite athletes, resistance, and/or endurance exercise would also require further attention. Ultimately, a combination of strategies capable to optimize muscle functionality, including bacteria (new microbes, bacterial ecosystems, or mix, more prone to colonize a specific gut ecosystem) associated with prebiotics and other ‘traditional’ supplements known to stimulate muscle anabolism (e.g. proteins), could be the best way to preserve muscle functionality in healthy individuals at all ages or patients.
... An improvement in the nutritional and immunological status of enterally-fed elderly subjects was observed by the administration of fermented milk containing Lactobacillus johnsonii La1 (Fukushima et al. 2007). A probiotic cheese containing L. acidophilus NCFM increased the cytotoxicity of NK cells in elderly volunteers (Ibrahim et al. 2010). In a study conducted by Lollo et al. (2013), on the effect of probiotic yoghurt and a probiotic whey beverage comprising S. thermophilus TA040, L. bulgaricus LB340, L. acidophilus LA14, and B. longum BL05 on immunomodulation after exhaustive treadmill exercise in Wistar rats, results demonstrated that the probiotic yoghurt outperformed the probiotic whey beverage in blood cell indicators (neutrophils and lymphocytes), cytokines (TNF-α and IL-1β), and various standard parameters. ...
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Probiotic species can beneficially influence human health by modulating and maintaining immune function in the gut. While prebiotics promote the growth of probiotics, their combinations with probiotics in synergistic way impart multifarious advantages to the host. Owing to their physiological benefits, demand for dairy and non‐dairy food products supplemented with probiotics and prebiotics is ever increasing. However, their incorporation in food products not only alters techno‐functional properties of food but also affects viability and bioactivity of these molecules. Hence, a careful selection of probiotics, prebiotics and food matrix besides optimizing food processing conditions is paramount for successful production of probiotic food.
... Cheese consumption has been demonstrated to reduce the risk factors associated with metabolic syndrome and body mass index. Consumption of probiotic cheese by elderly individuals promotes natural killer cell cytotoxicity and phagocytosis, thus proliferating immunomodulation (Ibrahim et al., 2010). Many health-promoting effects need to be validated with animal studies using specific models followed by clinical trials. ...
Article
Cheese is a product of ancient biotechnological practices, which has been revolutionized as a functional food product in many parts of the world. Bioactive compounds, such as peptides, polysaccharides, and fatty acids, have been identified in traditional cheese products, which demonstrate functional properties such as antihypertensive, antioxidant, immunomodulation, antidiabetic, and anticancer activities. Besides, cheese‐making probiotic lactic acid bacteria (LAB) exert a positive impact on gut health, aiding in digestion, and improved nutrient absorption. Advancement in biotechnological research revealed the potential of metabolite production with prebiotics and bioactive functions in several strains of LAB, yeast, and filamentous fungi. The application of specific biocatalyst producing microbial strains enhances nutraceutical value, resulting in designer cheese products with multifarious health beneficial effects. This review summarizes the biotechnological approaches applied in designing cheese products with improved functional properties.
... Fermented foods of many types are produced from animal and plant materials, some of which have the potential to provide additional health benefits through fermentation as functional foods [23,24]. Some fermented foods have beneficial immune, glycemic, and anti-inflammatory activities [25][26][27][28], whereas other fermented foods increase some inflammation markers [29]. These results indicate the necessity for assessment of each fermented food to assess its health-promoting activities because of differences in the materials and microbes used for fermentation. ...
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Although results of recent studies suggest that fermented foods strongly affect the gut microbiota composition and that they relieve inflammatory bowel disease symptoms, some reports have described that fermented foods increase some inflammation markers based on differences in fermented food materials. This study evaluated the effects of fermented plant extract (FPE) on dextran sulfate sodium (DSS)-induced colitis in mice and the effects on fecal microbiota composition in humans. Mice fed 5% FPE with 3% DSS (FPE group) showed no body weight loss, atrophy of colonic length, or bloody stool, similar to mice fed a basal diet (negative group), whereas mice fed 3% DSS (positive group) exhibited those effects. Concentrations of inflammation markers IL-6 and TNF-α were not significantly different between FPE and negative groups; however, those concentrations became higher in the positive group. 16S ribosomal RNA gene sequencing was used to characterize fecal microbiota in healthy women before and after 3-month FPE supplementation. The FPE supplementation induced increases in Firmicutes phyla and in Clostridiales order, which play a central role in inflammation suppression. These results suggest that FPE enhances Clostridiales growth in the gut and that it has an anti-inflammatory effect.
... Similarly, it was reported that the activity of phagocytes was significantly enhanced after the volunteers were given BB12 in the human trial (Schiffrin et al., 1997). Furthermore, Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus NCFM could significantly enhance NK cell activity in healthy elderly, while B. longum BB536 had no significant effect (Ibrahim et al., 2010;Akatsu et al., 2013). Therefore, not all strains have the ability to stimulate the activity of immune cells and the characteristics may reflect the strain-specific immune regulation. ...
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The microbiota is directly involved in the development and modulation of the intestinal immune system. In particular, members of the genus Bifidobacterium play a primary role in immune regulation. In the present study, Bifidobacterium bifidum H3-R2 was screened from 15 bifidobacterium strains by in vitro experiment, showing a positive tolerance to digestive tract conditions, adhesion ability to intestinal epithelial cells and a regulatory effect on immune cell activity. Immunostimulatory activity of B. bifidum H3-R2 was also elucidated in vivo in cytoxan (CTX)-treated mice. The results showed that the administration of B. bifidum H3-R2 ameliorated the CTX-induced bodyweight loss and imbalanced expression of inflammatory cytokines, enhanced the production of secretory immunoglobulin A (SIgA), and promoted splenic lymphocyte proliferation, natural killer (NK) cell activity and phagocytosis of macrophages in immunosuppressed mice. In addition, B. bifidum H3-R2 restored injured intestinal mucosal, and increased the villus length and crypt depth in CTX-treated mice. The results could be helpful for understanding the functions of B. bifidum H3-R2, supporting its potential as a novel probiotic for immunoregulation.
... Further, probiotic bacteria transformed more toxic forms to less toxic. For example, lactobacillus bacteria converts methylated mercury to inorganic mercury (Hg2+) then to Hg0, which is too poorly absorbed in gastrointestinal tract [ 61]. Meanwhile, ingestion of probiotics, including Bifidobacteria and Lactobacillus, increases neuron function and improves cognition via the gut-brain axis [62]. ...
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Different environmental toxins especially heavy metals exist in soil, water, and air recording toxic effect on human, animal, and plant. These toxicant elements are widespread in environment causing various disturbances in biological systems. Numerous strategies have been applied recently to alleviate heavy metal contamination; however, most of these strategies were costly and seemed unfriendly to our environment. Probiotics are living cell bacteria with beneficial characteristics for human health. Lactobacillus and Bifidobacterium are the major probiotic groups; however, Pediococcus, Lactococcus, Bacillus, and yeasts are recorded as probiotic. The vital role of the probiotics on maintenance of body health was previously investigated. Probiotics were previously recorded to its powerful capacity to bind numerous targets and eliminate them with feces. These targets may be aluminum, cadmium, lead, or arsenic. The current review discusses the history of probiotics, detoxification role of probiotics caused by heavy metals, and mechanism of their action that modulate different signaling pathway disturbance associated with heavy metal accumulation in biological system.
... Consumption of cheese prepared with L. rhamnosus HN001 and L. acidophilus NCFM having 10 9 CFU/day significantly enhanced the innate immunity in the elderly population with increased cytotoxicity of natural killer cells to kill the tumor cells. Moreover, increased phagocytic activity in addition to immune-stimulation was also observed in cheese fed to elders due to presence of starter culture (L. rhamnosus HN001 and L. acidophilus NCFM) (Ibrahim et al. 2010). Sharafedtinov et al. (2013) found in clinical study that protein rich full fat probiotic cheese (L. ...
... In a study on autistic children [10], probiotic supplementation was shown to lower the gastrointestinal distress in children with autism. Several studies reported the beneficial effect of probiotics in elderly people such as improvement in the immunological status [11][12][13], consumption of synbiotic shake (shake containing both probiotic and prebiotic) showed improvement in the glycemic status and cholesterol levels in elderly people with type 2 DM [14]. ...
Article
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Recent evidence indicates the use of probiotics in the prevention and treatment of diseases. Probiotics are capable of changing the gut microbiota composition and bile acid synthesis to elicit health benefits such as cholesterol-lowering, weight reduction, and improving insulin sensitivity. The aging population is prone to develop diseases because of their decreased physiological and biological systems. Probiotics are one of the promising supplements that may potentially counteract these detrimental effects. This review will discuss the influence of probiotics on bile acids in different populations-the elderly, obese individuals, and those with hypercholesterolemia, type 2 diabetes, hypertension, and non-alcoholic fatty liver disease.
... Several studies have documented probiotic effects on a variety of gastrointestinal and extra intestinal disorders, including prevention and alleviation symptoms of traveler's diarrhea and antibiotic associated diarrhea, inflammatory bowel disease (Marteau et al., 2002), lactose intolerance (de Vrese et al., 2001), protection against intestinal infections (Reid et al., 2001), and irritable bowel syndrome. Some probiotics have also been investigated in relation to reducing prevalence of atopic eczema later in life (Gueimonde et al., 2006), vaginal infections, and immune enhancement (Isolauri et al., 2001), contributing to the inactivation of pathogens in the gut, rheumatoid arthritis, improving the immune response of in healthy elderly people (Ibrahim et al., 2010), and liver cirrhosis. ...
... The processes of fermentation are different but most times this is done by using suitable condition for fermentation to occur for several days. In animals you can get (suya, kilishi) from beef, in Lactic acid bacteria, yeast 1-5 days Uzogara et al. (1990) Most commercial probiotic yogurt contain species of Lactobacillus rhamnosus as well as the yeast Saccharomyces boulardii have been demonstrated to possess in vitro affinity for toxic metals such as lead, mercury, arsenic and cadmium (Bisanz et al. 2014;Ibrahim et al. 2010). In recent times, probiotic foods have provided a nutritious and affordable means for people in developing nations to counter adverse effects accruing from toxic metal exposures. ...
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Probiotics are functional foods with a wide armamentarium of health benefits in man including metal chelation. Given the unacceptable blood lead levels and the near ignorance or negligence of heavy metals in both diagnoses and management of diseases in Nigeria, it is feared that these metals are involved in the aetiogenesis of several ailments from preeclampsia, metabolic syndrome, cancer, etc. This is an insight on Nigerian fermented foods and their possible role as metal chelators in the management of the chronic heavy metal exposure in Nigeria. One hundred and five articles fulfilled the inclusion criteria. Google scholar, PubMed and SCOPUS were searched for articles reporting fermented foods and probiotics in Nigeria. Only studies published in English Language were included, but there was no limitation in year of study. One hundred and five articles fulfilled the inclusion criteria. Studies from some African countries suggest that fermented foods of probiotics relevance have effectively shown metal chelation properties. Consumption of Nigerian fermented foods may hold a promise in checking the high body burden of heavy metals in Nigeria. Graphic abstract
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Functional foods are defined as foods that have health benefits beyond their inherent nutritional value. The incorporation of probiotics in food products is one of the most popular forms of such products and acceptable to most consumers. In this chapter, various industrial probiotic products are discussed, including the type of microorganisms used and the production process. Details of processing conditions and choice of probiotics for retaining the viability of the microorganism through production are included. Advanced non-food application of probiotics and the potential for such products are also presented.
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Age-associated immunological dysfunction (immunosenescence) is closely linked to perturbation of the gut microbiota. Here, we investigated whether syringaresinol (SYR), a polyphenolic lignan, modulates immune aging and the gut microbiota associated with this effect in middle-aged mice. Compared with age-matched control mice, SYR treatment delayed immunosenescence by enhancing the numbers of total CD3⁺ T cells and naïve T cells. SYR treatment induced the expression of Bim as well as activation of FOXO3 in Foxp3⁺ regulatory T cells (Tregs). Furthermore, SYR treatment significantly enhanced the Firmicutes/Bacteroidetes ratio compared with that in age-matched controls by increasing beneficial bacteria, Lactobacillus and Bifidobacterium, while reducing the opportunistic pathogenic genus, Akkermansia. In addition, SYR treatment reduced the serum level of lipopolysaccharide-binding protein, an inflammatory marker, and enhanced humoral immunity against influenza vaccination to the level of young control mice. Taken together, these findings suggest that SYR may rejuvenate the immune system through modulation of gut integrity and microbiota diversity as well as composition in middle-aged mice, which may delay the immunosenescence associated with aging.
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Scientific Reports 6 : Article number: 39026; 10.1038/srep39026 published online: 15 December 2016 ; updated: 31 January 2017 . The original version of this Article contained an error in the spelling of Sin-Hyeog Im, which was incorrectly given as Sin-Hyeog Lm.
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Milk and its derivatives are important food matrices when looking for the development of functional foods. Identifying the presence of autochthonous lactic acid bacteria with probiotic properties opens the way for the prospect of new isolates that are candidates for probiotics. Cheeses, fermented dairy products, ice cream, and infant formulas have been extensively explored in proposing new functional foods. Industry and consumers benefit from these studies, since probiotic food has the property of restoring the intestinal microbiota, which has been increasingly studied as responsible for the balance between the health-disease processes. Studies have advanced in the discovery of antiviral properties in probiotic bacteria, as well as in the development of recombinant probiotic bacteria. In this sense, this chapter aimed to explore the theme of probiotics considering the milk food matrix. The study of new microorganisms, products, and processes that assist in the development of new innocuous functional foods is also be presented.
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The intestinal microbiota changes in response to aging. The intestinal microbiota has a profound effect on the functioning of the intestine in health and disease. There are hormonal, immunological and neurological connections between the intestine and other organs systems in the body, and potentially vice versa. The intestinal microbiota may therefore have effects beyond the gut through so-called gut-microbiota-axes. Modulating, the intestinal microbiota with probiotics and/or prebiotics has been shown to have potential health benefits in the intestine and beyond. Especially in elderly, normal bodily functions such as bowel function, metabolic health and immune response have been observed to be beneficially influenced. However, many findings related to these gut-axes are emerging and not fully understood and especially the role in aging remains to be further investigated.
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Based on the probiotics ability, the genus Lactobacillus is frequently isolated from various fermented foods worldwide. Also, they have been used in novel foods preparation and fermented foods in pharmaceutical industries. In recent years, the more probiotic nature of novel indigenous microorganisms Lactobacillus is selected on the basis of its techno-functional characteristics nature. Among these, lactic acid bacteria (LAB) are usually considered as important and safe microbes for consumption as well as employed for detecting the rich probiotic characteristic microbes. Generally, LAB have more probiotic nature, including carbohydrate intolerance, and followed by digestion, maintaining the cholesterol level in blood, decrease the cancer cell formation, and enhance the antibiotic production in gastrointestinal and urogenital tracts. The current chapter has focused on industrial requirements, various probiotic microbes in fermented foods, and other techno-functional traits of probiotics that are used to human health benefit.
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Currently, functional foods with probiotics are very popular and there is an increasing interest in society to include them in diet. Until now, scientific research was focused on testing the beneficial effects of certain bacterial strains, regardless of origin, in humans. However, studies that describe the functional importance of species that are naturally present in food are not as abundant. Therefore, this work aims to analyse the microbiota of one of the most prominent microbial food ecosystems, that is cheese; and relate it to its functional properties. After analysing the microbial composition of different cheeses, such as Cheddar, Emmental, Gruyere, Camembert etc., it has been observed that many predominant species (for example, Lactobacillus acidophilus, Bifidobacterium infantis or Streptococcus thermophilus) are related to the treatment of health problems. Among others, they are effective in relieving lactose intolerance, preventing allergies, lowering cholesterol, inhibiting intestinal pathogens, treating inflammatory diseases or reducing the risk associated to mutagenicity and carcinogenicity. In addition, it has been proven that most strains maintain viability during cheese making and after the digestive process. In short, we would be faced with a functional food that is very beneficial for health.
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The stability of probiotic cultures has been seen as an issue for dairy manufacturers and consumers and this chapter reviews the technical and scientific aspects of probiotic dairy products. Probiotic micro-organisms are shown together with their main metabolic products. This provides some information on their possible role in flavour production, but it should be noted that the traditional lactic acid bacteria (LAB) (i.e. starter cultures) are mainly responsible for much of the flavour and aroma. For probiotic products, micro-organisms are selected for their various health benefits. A wide range of fermented milk products is made in many different countries. The classical example is yoghurt. Frozen yoghurt technology may be adopted for the inclusion of probiotic cultures into ice cream and frozen desserts. The viability of probiotic bacteria in yoghurt depends on the strains used, interaction between species present, production of hydrogen peroxide due to bacterial metabolism, and the final acidity of the product.
Article
Lactobacillus can effectively enhance the immune function of the body. The aim of this study was to evaluate the immunomodulatory effect of Lactobacillus rhamnosus 1.0320 on cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that CTX can successfully induce immunosuppression in mice. Compared with the CTX-induced immunosuppressed mice, Lactobacillus rhamnosus 1.0320 alleviated the body weight loss of mice and increased the spleen index and the thymus index. Lactobacillus rhamnosus 1.0320 significantly increased splenic lymphocyte proliferation, phagocytosis of neutral red by macrophages, NK cell activity, the carbon particle clearance index, delayed type hypersensitivity (DTH) and serum half-hemolysis concentration (HC50) in immunosuppressed mice. In addition, Lactobacillus rhamnosus 1.0320 could upregulate the serum levels of IL-6, IL-10, IL-12, TNF-α and IgG, restore the damage to the small intestine and liver tissue in immunosuppressed mice. Taken together, Lactobacillus rhamnosus 1.0320 can significantly enhance the immune function of immunosuppressed mice.
Article
Functional food is a relatively new concept, once there is not a worldwide definition, however, this term is increasingly widespread. The consumption of functional products is a new trend for the next years given the health improvement and well-being of its consumers. The dairy market has a great potential to be inserted in this trend due to the composition and the large variety of potentially functional dairy products. The non-thermal emerging technologies appeared as promising ways to improve product's benefits, and high intensity ultrasound and supercritical carbon dioxide seem to be great alternatives for dairy processing, improving some functional properties of its products.
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The immune system is the most effective barrier for the host to defend against the invasion of external pathogens. The system consists of a series of immune organs, immune cells, and immune active substances (immune molecules), which can detect and eliminate non-autologous substances, such as foreign pathogens and foreign bodies, and its own mutant cells. Among them, immune organs include bone marrow, spleen, lymph nodes, tonsils, small intestine collecting lymph nodes, appendix, thymus, etc.; immune cells include lymphocytes, mononuclear phagocytic cells, neutrophils, basophils, eosinophils, hypertrophy cells, platelets, etc.; immune molecules include the complement, immunoglobulin, interferon, interleukin, tumor necrosis factor, etc. Different types of immune tissues, immune cells, and immune molecules have different roles, and they coordinate the functions of various parts through lymphocyte recycling and various immune molecules.
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Elderly people are an important part of the global population who suffer from the natural processes of senescence, which lead to changes in the gut microbiota composition. These modifications have a great impact on their quality of life, bringing a general putrefactive and inflammatory status as a consequence. Some of the most frequent conditions related to this status are constipation, undernutrition, neurodegenerative diseases, susceptibility to opportunistic pathogens, and metabolic disbalance, among others. For these reasons, there is an increasing interest in improving their quality of life by non-invasive treatments such as the consumption of probiotics, prebiotics, and synbiotics. The aim of the present mini-review is to describe the benefits of these functional supplements/food according to the most recent clinical and pre-clinical studies published during the last decade. In addition, insights into several aspects we consider relevant to improve the quality of future studies are provided.
Article
In this study, the survival of the probiotics Lactobacillus acidophilus (LA-5), Lactobacillus casei subsp. paracasei (L. casei 01) and Bifidobacterium lactis (BB12) incorporated in a Brazilian semi-hard goat cheese (coalho) when exposed to in vitro simulated conditions of digestion was assessed. The inhibitory effects of these probiotic bacteria were also evaluated against Listeria monocytogenes and Staphylococcus aureus in the goat coalho cheese during refrigerated storage. At the end of the in vitro digestion, all of the probiotic tested strains presented decreased (p<0.05) viable cell counts (5.5-6.0logcfu/g) with respect to those determined before exposure to the mouth conditions (7-8logcfu/g). L. casei subsp. paracasei presented inhibition rate of 7.87% and 23.63% against S. aureus on the 14th and 21st day of storage at 10°C, respectively; against L. monocytogenes these values were 12.96 and 32.99%. Positive inhibition rates of B. lactis toward S. aureus were found on the 1st, 14th and 21st days of storage (16.32%, 10.12% and 3.67%, respectively); and against L. monocytogenes only on the 1st day of storage (3.28%). From these results, goat coalho cheese could be an interesting carrier of probiotic strains of L. acidophilus, L. casei subsp. paracasei and B. lactis. Moreover, L. casei subsp. paracasei, could be used as protective culture for delaying the growth of S. aureus and L. monocytogenes in goat coalho cheese.
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The aim of the study was to determine the effect of Saccharomyces cerevisiae, multienzyme composition supplementation on milk yield, quality, blood biochemical parameters of Lithuanian-Black-and-White cows. For this reason 28 cows were divided into four groups (three experimental and one control) each with seven cows fed balanced ration (control group) and following experimental groups: addition of 40g supplement of live yeast with organic selenium (group A); 40g supplement of live yeast with aromatic additives (group B); and 0.2g supplement of multienzyme composition (group C) during a 90 days period. The study showed that milk yield was 2.64%, 1.75%, 1.4% higher in groups A, B, C respectively, comparing with the control group. The milk SCC in experimental groups were lower comparing to the control group. The percentage of milk fat was significantly higher in group A - 0.33%, B - 0.31% and C - 0.16% comparing with the control group. All used additives ensure positive dynamics of investigated biochemical parameters in cattle blood. The results indicated that probiotic additives and multienzyme composition supplementation to dairy cows increased cows productivity and milk fat as well. Probiotic additives supplementation decreased SCC values in milk.
Article
Background Probiotics are microorganisms that promote beneficial health effects. To do this, they must survive passage through the gastrointestinal tract, adhere and colonize in the intestinal epithelium. Foods are vehicles that protect these strains during this passage, in particular cheese, which has advantages such as availability of nutrients, high pH, higher buffering capacity and low oxygen content. Thus, several studies have elaborated different types of probiotic cheeses and for evaluation of these products in vitro evaluations are performed of the viability of the microorganisms during processing, maturation, shelf life of the product, under simulated gastrointestinal conditions, modifications of the physical-chemical sensory properties of food matrixes, as well as extending the shelf life, among others, in addition to in vivo tests to verify the functional properties and mechanisms of action of strains in animals, and clinical trials in humans to prove the previous analyses. Scope and approach This review aims to approach probiotic characteristics by emphasizing research related to the use of cheeses as matrixes to carry these strains and in vitro or in vivo evaluations of these products. Key findings and conclusion The application of different probiotics in the most varied types of cheeses has been expanded due to the favorable characteristics of cheeses as carriers of these microorganisms, as well as the sensory effects of these strains in food matrixes. Well-conducted in vitro and in vivo tests are mandatory for validating these products according to regulatory institutions in order for the development of new probiotic cheeses to be efficient.
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Consumption of lactic acid bacteria (LAB) has been suggested to confer a range of health benefits including stimulation of the immune system and increased resistance to malignancy and infectious illness. In the present study, the effects of feeding Lactobacillus rhamnosus(HN001, DR20(TM)),Lactobacillus acidophilus(HN017)and Bifidobacterium lactis(HN019, DR10(TM))on in vivo and in vitro indices of natural and acquired immunity in healthy mice were examined. Mice were fed daily with L. rhamnosus, L. acidophilusor B. lactis(10(9) colony forming units) and their immune function was assessed on day 10 or day 28. Supplementation with L. rhamnosus, L. acidophilusor B. lactis resulted in a significant increase in the phagocytic activity of peripheral blood leucocytes and peritoneal macrophages compared with the control mice. The proliferative responses of spleen cells to concanavalin A (a T-cell mitogen) and lipopolysaccharide (a B-cell mitogen) were also significantly enhanced in mice given different LAB. Spleen cells from mice given L. rhamnosus, L. acidophilusor B. lactis also produced significantly higher amounts of interferon-gamma in response to stimulation with concanavalin A than cells from the control mice. LAB feeding had no significant effect on interleukin-4 production by spleen cells or on the percentages of CD4(+), CD8(+) and CD40(+) cells in the blood. The serum antibody responses to orally and systemically administered antigens were also significantly enhanced by supplementation with L. rhamnosus, L. acidophilusor B. lactis. Together, these results suggest that supplementation of the diet with L. rhamnosus(HN001),L. acidophilus(HN017)or B. lactis(HN019)is able to enhance several indices of natural and acquired immunity in healthy mice.
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Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, including the gastrointestinal tract. While this beneficial effect was originally thought to stem from improvements in the intestinal microbial balance, there is now substantial evidence that probiotics can also provide benefits by modulating immune functions. In animal models, probiotic supplementation is able to provide protection from spontaneous and chemically induced colitis by downregulating inflammatory cytokines or inducing regulatory mechanisms in a strain-specific manner. In animal models of allergen sensitization and murine models of asthma and allergic rhinitis, orally administered probiotics can strain-dependently decrease allergen-specific IgE production, in part by modulating systemic cytokine production. Certain probiotics have been shown to decrease airway hyperresponsiveness and inflammation by inducing regulatory mechanisms. Promising results have been obtained with probiotics in the treatment of human inflammatory diseases of the intestine and in the prevention and treatment of atopic eczema in neonates and infants. However, the findings are too variable to allow firm conclusions as to the effectiveness of specific probiotics in these conditions.
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Consumption of lactic acid bacteria (LAB) has been suggested to confer a range of health benefits including stimulation of the immune system and increased resistance to malignancy and infectious illness. In the present study, the effects of feeding Lactobacillus rhamnosus (HN001, DR20), Lactobacillus acidophilus (HN017) and Bifidobacterium lactis (HN019, DR10) on in vivo and in vitro indices of natural and acquired immunity in healthy mice were examined. Mice were fed daily with L. rhamnosus, L. acidophilus or B. lactis (10(9) colony forming units) and their immune function was assessed on day 10 or day 28. Supplementation with L. rhamnosus, L. acidophilus or B. lactis resulted in a significant increase in the phagocytic activity of peripheral blood leucocytes and peritoneal macrophages compared with the control mice. The proliferative responses of spleen cells to concanavalin A (a T-cell mitogen) and lipopolysaccharide (a B-cell mitogen) were also significantly enhanced in mice given different LAB. Spleen cells from mice given L. rhamnosus, L. acidophilus or B. lactis also produced significantly higher amounts of interferon-gamma in response to stimulation with concanavalin A than cells from the control mice. LAB feeding had no significant effect on interleukin-4 production by spleen cells or on the percentages of CD4+, CD8+ and CD40+ cells in the blood. The serum antibody responses to orally and systemically administered antigens were also significantly enhanced by supplementation with L. rhamnosus, L. acidophilus or B. lactis. Together, these results suggest that supplementation of the diet with L. rhamnosus (HN001), L. acidophilus (HN017) or B. lactis (HN019) is able to enhance several indices of natural and acquired immunity in healthy mice.
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NK cells are instrumental in innate immune responses, in particular for the early production of gamma interferon (IFN-γ) and other cytokines necessary to control certain bacterial, parasitic, and viral infections. NK cell-mediated effector functions are controlled by a fine balance between distinct receptors mediating activating and inhibitory signals; however, little is known about activating receptors on NK cells and their corresponding ligands. Several studies have shown that commensal lactobacilli isolated from the human gastrointestinal tract activate human mononuclear cells and are potent inducers of IFN-γ and monocyte-derived interleukin 12 (IL-12). NK cell activation was shown for Lactobacillus johnsonii La1. In this study the cellular mechanisms of in vitro NK cell activation by gram-positive bacteria were analyzed. Staphylococcus aureus- and L. johnsonii La1-mediated activation of CD3− CD16+ CD56+ human peripheral blood NK cells, including expression of the activation antigen CD69 and secretion of IFN-γ, required cell contact-dependent costimulation by autologous monocytes. S. aureus- and L. johnsonii-preactivated monocytes retained their capacity to induce NK cell activation. In contrast, cytokine-primed monocytes completely failed to induce NK cell activation unless bacteria were present. This suggests that phagocytosis of bacteria provided additional coactivation signals on accessory cells that may differ from those induced by tumor necrosis factor and IFN-γ. Blocking of costimulatory molecules by B7.1, B7.2, and IL-12 but not CD14 monoclonal antibodies inhibited S. aureus- and L. johnsonii-induced effector function of NK cells. Our data suggest an important role for accessory cell-derived signals in the process of NK cell activation by gram-positive bacteria.
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The immunomodulatory properties of lactic acid bacteria (LAB) and foods containing them (e.g., fermented milks) is a topic currently under investigation. Individuals could potentially benefit from the inclusion of LAB in the diet at different times during the life cycle. One of the most accepted specific uses of probiotic bacteria is the prevention of atopic eczema in infants with family history of the disease who receive the probiotic bacteria early, through supplementation of the gestating mother and orally after birth. Immune enhancing effects have also been suggested to be beneficial in diarrhoea treatment, especially in children infected with rotavirus and in malnourished patients, infants and adolescents, whose capacity to produce IFN-gamma can be increased after LAB-containing yoghurt intake. Regarding young people and adults, investigations have been conducted exploring the immunomodulation by LAB in subjects under stressful situations, in the prevention of urinary tract infections in fertile women and in the treatment of allergy. However, the beneficial effects of probiotics in these conditions remain controversial and the scientific evidence provided so far is not considered to be conclusive. The elderly population has been the focus of investigations aimed at identifying the capacity of probiotics to counteract the immunosenescence process by increasing phagocytic and natural killer (NK) cell activities and to protect against infection. The mechanisms involved in the different effects attributed to LAB remain to be clarified. Moreover, considering that the immunomodulatory properties are strain-specific, defining the optimal dose of a certain bacteria or combination of bacteria strains and the duration of treatment for a desired effect in a target population group is essential in order to substantiate health claims.
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Advanced age is associated with defects in all of the cells of the innate immune system, including numbers, function, and early stages of activation. This review, presents the current state of the field on the impact of age on the innate immune system. The analysis of the literature suggests that a dysfunctional innate immune system is a contributing factor to aberrant outcomes after injury or infection and to the development of many of the diseases observed in the elderly. Gaining an understanding of the nature of the defects in innate immune cells may allow the development of therapeutic strategies aimed to restore innate immune function in aged individuals.
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Consumption of some species and strains of lactic acid bacteria (LAB) has been shown to enhance immunity in humans. In this study, the effect of dietary supplementation with Lactobacillus rhamnosus HN001 (DR20™), a newly characterized LAB strain, on immune cell function in healthy elderly subjects was investigated. The study comprised three stages, each lasting 3 weeks. In stages 1 (run-in) and 3 (washout), subjects (n = 13) received low fat milk (LFM, 200 mL twice daily) as a base diet. In Stage 2 (supplement intervention), subjects received LFM supplemented with L. rhamnosus HN001 (1.25 × 108 CFU/mL). Assessment of immune function was made at the beginning, and the end of each stage. Consumption of milk supplemented with L. rhamnosus HN001 for three weeks resulted in a significant increase in the phagocytic activity of peripheral blood polymorphonuclear cells and monocytes. These responses returned to baseline following 3 weeks washout with un-supplemented milk. This suggests that L. rhamnosus HN001 is able to enhance aspects of natural immunity in humans, and could be used as a dietary adjunct for optimizing immune responsiveness in the elderly.
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In this study, probiotics Lactobacillus acidophilus NCFM and Lactobacillus rhamnosus HN001 in cheese were studied using models simulating the human gastrointestinal tract with the aim of investigating whether the cheese matrix affected the survival and metabolic properties of these probiotic strains. Probiotics in cheese survived in the simulated upper gastrointestinal tract model, and numbers of L. acidophilus, L. rhamnosus and total lactobacilli were increased in the colonic fermentation simulations of the probiotic cheese when compared with the non-probiotic cheese used as a control. The cheese matrix also beneficially affected cyclooxygenase-gene expression of colonocytes in a cell culture model. Freeze-dried probiotics, which were also analysed in the colonic simulator, showed similar changes in Lactobacillus numbers, although gave a stronger increase and also affected other microbial groups. These results indicate that the probiotic microbes in cheese survive in the gastrointestinal tract and that the cheese matrix does not seem to affect the probiotic survival.
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The safety of the probiotic lactic acid bacteria Lactobacillus acidophilus (HN017), Lactobacillus rhamnosus (HN001, DR20™), and Bifidobacterium lactis (HN019, DR10™), was studied in BALB/c mice fed with different doses (5×107, 109 or 5×1010 cfu/mouse/day) of the bacteria for 7 days. No abnormal clinical signs were observed in any of the groups during the period of the experiment. There were no significant differences in feed intake, water intake, or liveweight gain among mice fed the different probiotics, in comparison to a control group which was not fed with LAB. No bacteria were detected in the spleen of any animals. Although one mouse from each of the groups fed with Lb. rhamnosus HN001 or B. lactis HN019 had lactic acid bacteria detected in their kidney, DNA finger-printing analysis showed that the isolates were different from the test probiotic strains. Histological and haematological parameters also indicated that the lactic acid bacterial strains did not adversely affect the health of the mice.
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A flow cytometry based method has been developed to assess natural killer (NK) cell activity in both short-term (4 h) and long-term (18 h) NK assays. Target cells were either labeled with PKH-2, c′FDA or D275. Simultaneously, dead cells were identified by counter-staining with the nuclear dye propidium iodide. Using flow cytometry, only D275 in combination with propidium iodide permits the differentiation of four cell populations: live target cells, dead target cells, live effector cells, and dead effector cells. Even after the extended incubation periods (18 h) necessary for the determination of NK activity in some domestic animals these four populations remain clearly distinguishable. Comparison of results with cells of normal human individuals obtained using this D27S/propidium iodide flow cytometry assay with data derived from fluorescence microscopy or an endogenous lactate dehydrogenase release assay shows a strong correlation. Since in long-term NK assays a high proportion of dead effector cells is constantly observed this cell population frequently limits the use of the lactate dehydrogenase release assay but does not interfere with the flow cytometry assay presented here. Using this novel assay, we have demonstrated the suppressive effects of defined glycosaminoglycans on long-term porcine NK activity.
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Introduction: During aging, dysregulated immune functions occur contributing to increased susceptibility to morbidity and mortality. However, these dysregulations are normally counterbalanced by continuous adaptation of the body to the deteriorative changes occurring over time. These adaptive changes well occur in healthy centenarians. Discussion: Both innate (natural) and adaptive (acquired) immune responses decline with advancing age. Natural killer (NK) and natural killer T (NKT) cell cytotoxicity, representing one of best models of innate immune response, decreases in aging as well as interferon-gamma (IFN-gamma) production by both activated types of cells. Both NK and NKT cell cytotoxicity and IFN-gamma production increase in very old age with respect to normal aging, especially by NKT cells bearing TCRgammadelta. The role played by zinc and metallothioneins (MT) is crucial because this affects NK and NKT cell development, maturation, and functions. In particular, some MT polymorphisms are involved in maintaining innate immune response and intracellular zinc ion availability in aging with thus a role of MT genetic background to escape some age-related diseases with subsequent healthy aging and longevity.
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Experimental and clinical data demonstrate that ageing is associated with the gradual deterioration of the immune system, generally referred to as immunosenescence. Age-related immune dysfunction may have an impact not only on the incidence of cancer, but also on the preventive and therapeutic approaches, which are based on immune system activation. Over the last few years the use of immunological measures to prevent cancer in experimental mouse models involving preimmunization with new vaccines against even a poor or apparently non-immunogenic tumour has yielded worse outcomes in older age than in young adults. Different mechanisms, which may be due to age-related numerical or functional dysfunction of immune cells and/or to tumour microenvironmental changes, could be responsible for this defect. This review summarises the impact of immunosenescence on the effectiveness of cancer vaccines, knowledge of cancer immunisation in old age and the potential mechanisms implicated in the poorer effectiveness of anticancer immune-based approaches in advanced age. Several approaches to, and possibilities of correcting the low effectiveness of immunisation procedures in old age are described.
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A recently developed simple and rapid fluorescence assay of phagocytosis by polymorphonuclear leucocytes (PMNs) was used to compare the phagocytic activity of PMNs from diabetic patients and healthy people. Differences in phagocytosis have been described in these systems. Different bacterial strains were used to challenge the phagocytic capabilities of bacterial ingestion and killing for both patient and control groups. Staphylococcus epidermidis derived from clinical isolates was prone to faster ingestion and more rapid killing once the bacteria were intracellular, compared with S. epidermidis derived from normal skin. The pathogen, S. aureus, though ingested rapidly, was not so easily killed. PMNs from diabetics appeared to ingest S. aureus and kill ingested pathogenic bacteria not as effectively as PMNs from healthy volunteers. These difference were not found for non-pathogenic skin isolates of S. epidermidis.
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A whole blood assay for assessment of spontaneous or NK-cell activity has been proposed in order to avoid many of the problems encountered with the conventional methods involving cell separation procedures. Normal subjects and patients with cancer of the kidney or bladder were investigated with the new method. Cancer patients were found to exhibit significantly lower levels of reactivity when compared to normal subjects; furthermore, the results were consistent with the common belief that tumor burden and NK activity were inversely related. The whole blood assay appears useful in monitoring cancer patients, particularly those treated with immune modulators.
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The general safety of immune-enhancing lactic acid bacteria (LAB) strains Lactobacillus rhamnosus HN001 (DR20), Lb. acidophilus HN017, and Bifidobacterium lactis HN019 (DR10) was investigated in a feeding trial. Groups of BALB/c mice were orally administered test LAB strains or the commercial reference strain Lb. acidophilus LA-1 at 2.5 x 10(9), 5 x 10(10) or 2.5 x 10(12) colony forming units (CFU)/kg body weight/day for 4 weeks. Throughout this time, their feed intake, water intake, and live body weight were monitored. At the end of the 4 week observation period, samples of blood, liver, spleen, kidney, mesenteric lymph nodes, and gut tissues (ileum, caecum, and colon) were collected to determine: haematological parameters (red blood cell and platelet counts, haemoglobin concentration, mean corpuscular volume, mean corpuscular haemoglobin, and mean corpuscular haemoglobin concentration); differential leukocyte counts; blood biochemistry (plasma total protein, albumin, cholesterol, and glucose); mucosal histology (epithelial cell height, mucosal thickness, and villus height); and bacterial translocation to extra-gut tissues (blood, liver, spleen, kidney and mesenteric lymph nodes). DNA finger printing techniques were used to identify any viable bacterial strains recovered from these tissues. The results demonstrated that 4 weeks consumption of these LAB strains had no adverse effects on animals' general health status, haematology, blood biochemistry, gut mucosal histology parameters, or the incidence of bacterial translocation. A few viable LAB cells were recovered from the tissues of animals in both control and test groups, but DNA fingerprinting did not identify any of these as the inoculated strains. The results obtained in this study suggest that the potentially probiotic LAB strains HN001, HN017, and HN019 are non-toxic for mice and are therefore likely to be safe for human use.
Article
Background: One of the most critical questions in immunosurveillance is whether differences between individuals with regards to natural immunological host defence can predict future development of cancer. Although this question has so far remained open, there are clear indications of significant roles of several naturally cytotoxic lymphocytes in preventing the development of cancer. We began a prospective cohort study among a Japanese general population in 1986, using various immunological and biochemical markers. Methods: Natural cytotoxic activity of peripheral-blood mononuclear cells was assessed by isotope-release assay in 3625 residents of a Japanese population mostly older than 40 years of age, between 1986 and 1990. Immunological and biochemical markers were also measured, and participants were given a questionnaire on lifestyle. We did an 11-year follow-up survey of the cohort members looking at cancer incidence and death from all causes, and analysed the association between cytotoxic activity of peripheral-blood lymphocytes assessed at baseline and cancer incidence found in the subsequent follow-up. Findings: 154 cancer cases were used in the analysis. When we categorised the cytotoxic activity of peripheral-blood lymphocytes by tertiles, age-adjusted relative risk of cancer incidence (all sites) was 0.72 (95% CI 0.45-1.16) for men with high cytotoxic activity, and 0.62 (0.38-1.03) for men with medium cytotoxic activity, taking the risk of those with low cytotoxic activity as reference. For women with high cytotoxic activity relative risk was 0.52 (0.28-0.95), and for those with medium cytotoxic activity 0.56 (0.31-1.01). For both sexes with high and medium cytotoxic activity risk was 0.63 (0.43-0.92) and 0.59 (0.40-0.87), respectively. Interpretation: Our results indicate that medium and high cytotoxic activity of peripheral-blood lymphocytes is associated with reduced cancer risk, whereas low activity is associated with increased cancer risk suggesting a role for natural immunological host defence mechanisms against cancer.
Article
To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). A three stage, pre-post intervention trial, spanning nine weeks. Taipei Medical College Hospital, Taipei, Taiwan. Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.
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Congenital patients who lack natural killer (NK) cell activity experience repeated polymicrobial infections. NK cell activity varies significantly among normal people, but it is unknown whether this variation influences their ability to fight infections. This study examined this concern. NK cell activity and other variables, i.e. age, sex, performance status (PS), serum albumin value, lymphocyte and neutrophil counts, various lymphocyte subsets, etc. were determined for 108 immunologically normal elderly subjects who were in nursing homes due to an impaired PS. We analysed for correlations between these variables and the follow-up results of the subjects. Forty-eight subjects developed infection(s) during the first year of follow-up. A low NK cell activity was associated with the development of infection (P = 0.0105, multivariate logistic regression analysis). The relative risk for the development of infection increased in accordance with the decrease in the NK cell activity. Eleven subjects died of infection during the study period. A low NK cell activity was associated with short survival due to infection (P = 0.0056, multivariate Cox's proportional-hazards regression analysis). Our data indicate that low NK cell activity is associated with development of infections and death due to infection in immunologically normal elderly subjects with an impaired PS.
Article
Many elderly subjects are at increased risk of infectious and noninfectious diseases due to an age-related decline in lymphoid cell activity (immunosenescence). Noninvasive means of enhancing cellular immunity are therefore desirable in the elderly. Previous reports have suggested that dietary supplementation could represent an effective means of enhancing the activity of circulating natural killer (NK) cells in the elderly. In the present study, we have conducted a pre-post intervention trial to determine the impact of dietary supplementation with probiotic lactic acid bacteria (LAB) on peripheral blood NK cell activity in healthy elderly subjects. Twenty-seven volunteers consumed low-fat/low-lactose milk supplemented with known immunostimulatory LAB strains (Lactobacillus rhamnosus HN001 or Bifidobacterium lactis HN019) for a period of 3 weeks. A dietary run-in of milk alone was shown to have no significant effect on NK cells. In contrast, the proportion of CD56-positive lymphocytes in peripheral circulation was higher following consumption of either LAB strain, and ex vivo PBMC tumoricidal activity against K562 cells was also increased. Supplementation with HN001 or HN019 increased tumoricidal activity by an average of 101 and 62%, respectively; these increases were significantly correlated with age, with subjects older than 70 years experiencing significantly greater improvements than those under 70 years. These results demonstrate that dietary consumption of probiotic LAB in a milk-based diet may offer benefit to elderly consumers to combat some of the deleterious effects of immunosenescence on cellular immunity.
Article
Habitual smoking significantly reduces natural killer (NK) cell activity. To clarify whether the intake of fermented milk containing lactic acid bacteria restores NK cell activity in habitual smokers, we conducted a placebo-controlled double-blind test. Ninety-nine subjects with smoking habits were randomly divided into two groups and daily for 3 weeks were given fermented milk containing Lactobacillus casei or placebo. NK cell activity in the peripheral blood mononuclear cells (PBMNC) was determined before and after the intake. Average number of cigarettes smoked and number of cigarettes that the subjects smoked before giving blood after getting up on the inspection day were asked, and these data were used to adjust the influence of smoking on NK cell activity. NK cell activity in individuals was inversely correlated to numbers of cigarettes smoked. Averaged NK cell activity adjusted by the numbers of cigarettes was significantly higher in individuals drinking fermented milk containing L. casei than those drinking a placebo. However, the proportion of NK cells was not different between individuals drinking either fermented milk containing L. casei or the placebo. Intake of fermented milk containing lactic acid bacteria was considered effective for restoring the NK cell activity of habitual smokers.
Article
We have reported previously that Lactobacillus casei ssp. casei, together with specific substrate dextran, exhibited an adjuvant effect of stimulating humoral immune responses against bovine serum albumin (BSA) as a model antigen in BALB/c mice. In the present study, among the Lactobacillus species tested, L. casei ssp. casei with dextran significantly elevated the natural killer (NK) cell activities in spleen mononuclear cells from BALB/c mice in comparison to L. casei ssp. casei alone or other Lactobacillus species with or without dextran. Oral administration of L. casei ssp. casei together with dextran also resulted in a significant increase of NK cell activities in healthy human volunteers. Further, L. casei ssp. casei induced significant production of interleukin (IL)-12 in human peripheral blood mononuclear cells and IL-15 mRNA expression in the human intestinal epithelial cell line Caco-2. L. casei ssp. casei with dextran in food also significantly elevated the survival rate of BALB/c mice bearing Meth-A cells. Taken together, these results demonstrate that dietary synbiotic supplementation which is a combination of the L. casei ssp. casei used as a probiotic together with the dextran, a specific substrate as a prebiotic, efficiently elicits murine and human NK cell activities.
Article
Nine healthy middle-aged and 10 elderly volunteers drank fermented milk containing 4 x 10(10) live cells of Lactobacillus casei strain Shirota daily for 3 wk, and their natural killer (NK) activity and other immunological functions were examined. In the experiments with middle-aged volunteers, NK activity significantly increased (P<0.01) 3 wk after the start of intake, elevated NK cell activity remained for the next 3 wk, and this effect was particularly prominent in the low-NK-activity individuals. In the experiments with elderly volunteers, NK activity significantly decreased (P<0.01) in the control group 3 wk after the start of intake; however, the intake of Lactobacillus casei strain Shirota maintained the NK activity. These results suggest that daily intake of Lactobacillus casei strain Shirota provides a positive effect on NK-cell activity.
Article
It is now becoming apparent that the immune system undergoes age-associated alterations, which accumulate to produce a progressive deterioration in the ability to respond to infections and to develop immunity after vaccination, both of which are associated with a higher mortality rate in the elderly. Immunosenescence, defined as the changes in the immune system associated with age, has been gathering interest in the scientific and health-care sectors alike. The rise in its recognition is both pertinent and timely given the increasing average age and the corresponding failure to increase healthy life expectancy. This review attempts to highlight the age-dependent defects in the innate and adaptive immune systems. While discussing the mechanisms that contribute to immunosenescence, with emphasis on the extrinsic factors, particular attention will be focused on thymic involution. Finally, we illuminate potential therapies that could be employed to help us live a longer, fuller and healthier life.
Article
Aging is associated clinically with increases in the frequency and severity of infectious diseases and an increased incidence of cancer, chronic inflammatory disorders and autoimmunity. These age-associated immune dysfunctions are the consequence of declines in both the generation of new naïve T and B lymphocytes and the functional competence of memory populations. These alterations collectively are termed immunosenescence.
Article
Aging is a complex process that negatively impacts the development of the immune system and its ability to function. Progressive changes in the T and B cell systems over the life span have a major impact on the capacity to respond to immune challenge. These cumulative age-associated changes in immune competence are termed immunosenescence. This process is mostly characterized by: (1) shrinkage of the T cell repertoire and accumulation of oligoclonal expansions of memory/effector cells directed toward ubiquitary infectious agents; (2) involution of the thymus and the exhaustion of naive T cells; and (3) chronic inflammatory status. Here we discuss possible strategies to counteract these main aspects of immunosenescence, in particular the role of the normalization of intestinal microflora by probiotics. A better understanding of immunosenescence and the development of new strategies to counteract it are essential for improving the quality of life of the elderly population.
Probiotic supplementation to enhance natural immunity in the elderly
  • Gill HS
  • Rutherfurd KJ
  • Gill HS
  • Rutherfurd KJ
NK and NKT cells in aging and longevity
  • Mocchegiani E
  • Giacconi R
  • Cipriano C
  • Malavolta M
  • Mocchegiani E
  • Giacconi R
  • Cipriano C
  • Malavolta M
Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, World Population Prospects: The
World Population Prospects (2008) Population Division of the Department of Economic and Social Affairs of the United Nations Secretariat, World Population Prospects: The 2008 Revision. Available at http://esa.un.org/unpp. Accessed on 24 June 2009.