Skip to content

Advertisement

Immunity & Ageing

Open Access

The interaction between gut microbiota and age-related changes in immune function and inflammation

Immunity & Ageing201310:31

https://doi.org/10.1186/1742-4933-10-31

Received: 23 November 2012

Accepted: 10 May 2013

Published: 5 August 2013

Abstract

Intestinal microbiota and gut immune systems interact each other, maintaining a condition of homeostasis in the context of the intestinal habitat. However, both systems undergo modifications in elderly, thus accounting for a low grade inflammatory status which, in turn, may evolve toward more severe pathological conditions such as inflammatory bowel disease and colon rectal cancer. In addition, in western societies dietary habits may negatively influence the microbiota composition, also altering gut immune response which is per se impaired in elderly. In order to prevent the outcome of aged-related disease, supplementation of nutraceuticals able to correct abnormalities of both immune system and microbiota has become more frequent than in the past. In this respect, a better identification of components of the aged microbiota as well as a deeper analysis of gut mucosal immunity function should be pursued.

Keywords

AgeingGutImmunityMicrobiota

Introduction

The intestinal microbiota is mostly confined in the colon where resides 1.5 Kg of microbes that is equal to about 1014 microorganims [1]. Human microbiota represents a “superorganism” possessing more genes than the human genome [2]. It undergoes individual variations in its composition and, in the same individual, variations in the different segments of the bowel have been reported [3]. Moreover, the microbiota of the mucosa seems to differ from that of the lumen and not always a direct interaction between microbiota and epithelial cells does occur [4]. Actually, two major phyla have been identified in the animal and human microbiota, such as Bacteroidetes (Gram-negative bacteria) and Firmicutes (Gram-positive bacteria). However, Actinobacteria and Protobacteria can predominantly colonize the intestine in some people [5, 6].

In the context of the gut associated lymphoid tissue (GALT), enterocytes or intestinal epithelial cells (IECs) represent the first barrier against invading microorganisms either secreting mucin or defensins (a class of antimicrobial peptides) or sensing pathogens via Toll-like receptors (TLRs) [7]. Furthermore, microfolding (M) cells, specialized IEC, are able to sample microbial antigens and transfer them to lamina propria (LP) immune cells [e.g., dendritic cells (DCs)] [8]. In turn, DCs act as presenting antigen cells (APCs), thus triggering both harmful and protective responses in the host [9]. DCs in the presence of a milieu enriched in interleukin (IL)-6, IL-1β and transforming growth factor (TGF)-β are able to polarize the immune response towards T helper (h)17 cells which, in turn, release IL-17A, IL-17 F, IL-21 and IL-22, thus becoming inflammatory in the presence of IL-23 [10]. This immune pathway is mainly activated in the course of inflammatory bowel disease (IBD).

On the other hand, CD103+ cells are tolerogenic and in the presence of IL-10, TGF-β, thymic stromal lymphopoietin and vasoactive intestinal peptide induce T regulatory (Treg) cells [11]. These CD4 + CD25 + FoxP3+ cells release IL-10 in the bowel, counteracting the activity of Th17 cells [12]. This tolerogenic anti-inflammatory activity is favored by retinoic acid (RA), a metabolite of vitamin A, produced by CD103+ tolerogenic DCs [13]. Of note, RA seems to directly interfere with Th17 polarization. In the context of intestinal mucosa, secretory (s) IgA production by B cells prevents bacterial adhesion to mucosal surfaces and neutralize toxins.

Regulation of the intestinal immune homeostasis by the microbiota is illustrated in Figure 1.
Figure 1

Immune homeostatis maintained by the intestinal microbiota. The equilibrium between Bacteroidetes and Firmicutes leads to the activation of T regulatory cells with production of the anti-inflammatory cytokine IL-10. On the other hand, release of IL-17 by Th17 cells is reduced.

In aged GALT, a marked multiple impairment of the immune response has been reported as evidenced by several studies conducted in animal models [14]. Major alterations are represented by [15]:
  1. 1.

    Reduced secretion of mucus and α-defensin;

     
  2. 2.

    Easy entry of pathogens into the mucosal layers and generation of a low grade inflammatory response (the so-called “inflamm-ageing”) [16] with Th1, Th2 and Th17 cell polarization.

     

This condition of inflamm-ageing [16] is perpetuated by overgrowth of intestinal pathobionts.

Interactions between intestinal microbiota and immune system

Microbiota and immune cells actively interact within the gut [17]. Evidence has been provided that Bacteroides fragilis induces production of IL-10 by Treg cells via recognition of the polysaccharide A by TLR-2 [18]. In addition, lactobacilli and bifidobacteria play a tolerogenic role, rendering DCs less undifferentiated [19]. Conversely, segmented filamentous bacteria (SFB), component of the animal microbiota, are able to induce production of IL-17 from Th17 cells in mice [20]. Therefore, a fine balance is required in the daily interplay between microbiota and innate and adaptive immune cells to avoid noxious reactions to the host. According to the two-hit model [21] alteration of the microbiota triggers IL-6 production by lamina propria DCs, thus leading to activation of T0 cells. Differentiation of T0 cells into Th1 cells and Th17 cells creates an inflammatory milieu which culminates in colitis (Figure 2).
Figure 2

The two-hit model in experimental colitis. Alteration of the microbiota leads to the activation of DCs which produce IL-6 (first hit). In turn, IL-6 activates T0 cells which differentiate into Th1 cells and Th17 cells, respectively. This polarization of the immune response generates production of inflammatory cytokines (second hit).

Studies on the aged intestinal microbiota have led to conflicting results. A decline of bifidobacteria and lactobacilli has been reported in the elderly with an increase of Bacteroides and facultative anaerobes [22, 23]. In contrast, others reported higher levels of Ruminococcus and lower levels of Eubacterium and Bacteroides [24] with higher levels of bifidobacteria in comparison with the younger counterpart [25]. Finally, no differences between aged and younger individuals have been reported by others except for higher numbers of aerobes in elderly [26]. Also differences in aged microbiota were found depending on the country examined. In this respect, in a small population of aged Italian subjects an unchanged level of Bacteroidetes and an increase in Faecalibacterium spp. were observed [27]. Viceversa in a large cohort of Irish elderly people Bacteroidetes and Faecalibacterium spp. remarkably increased [22]. In the above mentioned group of Italian people no differences in microbiota were found when young adults (30 yrs old) and elderly (70 yrs old) were compared. Conversely, in the same group, centenarians exhibited a different composition of their microbiota. While Bacteroidetes and Firmicutes were still present with levels comparable to those of younger adults, a decrease of Clostridium cluster XIVa, an increase in bacilli and rearrangement of Clostridium cluster IV were reported [27]. In addition, in centenarians the observed increase in Proteobacteria, the so-called “pathobionts”, may explain the high frequency of infections once these bacteria have escaped from the host immune response [28].

Microbiota components account for the production of short chain fatty acids (SCFA) and, in particular butyrate, acetate and propionate. SCFA are endowed with anti-inflammatory (inhibition of NF-κB) and anti-neoplastic activities, also exerting a protective function in favor of intestinal epithelia [29]. In fact, butyrate has been shown to provide energy to the intestinal epithelium, as suggested by epithelial atrophy and inflammation in diversion colitis owing to SCFA deficiency [30]. In aged people, evidence has been provided that reduction of butyrate levels is depending on the decreased number of Faecalibacterium (F.) prausnitzii, Eubacterium hallii and Eubacterium rectal/Roseburia group [27]. Therefore, SCFA decrease may lead to an impaired secretion of mucins by the IECs and, therefore, easier entry of pathogens into the intestinal mucosa, especially Enterobacteriaceae. These Gram-negative bacteria are able to release lipopolysaccharides or endotoxins, which, in turn, aggravate the inflammatory condition [31]. In general terms, patients with IBD exhibit an abnormal microbiota with instability of dominant species which is higher than in healthy controls. In particular, F. Prausnitzii is severely reduced in Chron’s disease and in ulcerative colitis with an increased prevalence of adherent-invasive E. coli strains. However, the question is still open whether this alteration of microbiota is the cause or the consequence of IBD [32]. Moreover, evidence has been provided for a decreased content of SCFA in colon rectal cancer (CRC) with an increase of CRC in the western elderly population. A condition of chronic inflammation dependent on the change of microbiota leading to TLR-mediated NF-κB activation and colonization of the bowel by toxigenic bacterial strains, such as Helicobacter pylori, Bacteroides fragilis and Escherichia coli seems to contribute to the pathogenesis of CRC [33]. In this framework, in a recent study a comparison of aged microbiota was made between community-dwelling individuals and long-stay individuals. Actually, SCFA fecal content was more pronounced in community group than in long-stay patients [34]. In the latter, IL-6, IL-8 and C-reactive protein levels were higher than in the former group, as expression of a status of systemic inflammation. All these evidences correlated to a change in microbiota since in community individuals a higher numbers of Firmicutes and lower numbers of Bacteroidetes than those observed in long-stay patients were detected [34]. This situation is depicted in Figure 3 where the activation of Th17 cells leads to a condition of inflammation.
Figure 3

Effects of altered microbiota in the intestinal immune response in elderly people. Even if data on the aged microbiota are still controversial, in some cases increase of Firmicutes and decrease of Bacteroidetes may lead to a switch of the immune response towards an inflammatory profile with activation of Th17 cells.

In this context, one should emphasize that obesity leads to an alteration of intestinal microbiota with an increase of Firmicutes [35], thus provoking a further aggravation of inflamm-ageing.

Nutraceutical interventions in elderly

Nowadays, an arsenal of dietary products is available for the restoration of microbiota in young and elderly population [36]. Prebiotics, as non digestible components of fruits, vegetables and grain, are oligosaccharides able to accelerate the growth of gut anaerobes with production of SCFA [29, 37]. Probiotics are viable bacteria [38] which enhance intestinal epithelial functions such as production of mucus, defensins and sIgA [39]. Moreover, probiotics upregulate phagocytic and natural killer (NK) cell functions, also inducing activation of Treg cells [4042]. Probiotics and symbiotics (a mix of prebiotics and probiotics) have been proven to be beneficial when administered to aged people. For instance, supplementation of Bifidobacterium (B.) lactis HN 019 to aged individuals led to the recovery of granulocyte and NK cell activities [43]. Oral intake of Lactobacillus (L.) pentosus strain b240 (b240) has been shown to augment sIgA secretion in elderly people. Moreover, b240 was able to reduce frequency of common cold in aged individuals, likely acting via mucosal immunity [44]. In a double-blind trial B. lactis BL-01 and B. bifidum BB-02 along with inulin as a prebiotic could increase numbers of B. bifidum and total bifidobacteria and lactobacilli in the microbiota of elderly subjects [45]. Modification of microbiota seems to represent an essential event for less frequency of winter infections to occur. In a recent trial, administration for one month of fermented cow milk containing L. rhamnosus and oligofructose (a symbiotic) to free-living elderly increased serum levels of IL-1, IL-6, and IL-8, while reduced basal levels of IL-12, IL-10 and tumor necrosis factor (TNF)-α were not modified by this treatment [46]. It is likely that induction of a more vigorous acute phase response in these subjects may compensate the impaired adaptive immune response in the case of pathogen invasion.

Main functions of prebiotics and probiotics are represented in Figure 4.
Figure 4

Illustration of major activities of probiotics and prebiotics.

Polyphenols, compounds widely present in the vegetal kingdom, have been shown to influence the composition of the gut microbiota. Consumption of blueberry [47], grape juice [48] and red wine or gin [49], respectively, mainly increased Bifidobacterium spp. in fecal samples from human volunteers. In addition, our recent studies have demonstrated that polyphenols contained in red wine or in fermented grape marc exhibit an anti-inflammatory role both in vitro[50] and in vivo[51]. Particularly, in vitro induction of human Treg cells and in vitro attenuation of colitis in mice with decrease of IL-1β and TNF-α content in homogenized colon seem to sustain the anti-inflammatory activities of polyphenols. Therefore, intake of dietary polyphenols in the elderly may beneficially act either on microbiota restoration and, consequentially, on attenuation of chronic inflammatory conditions.

In this framework, deficiencies of micronutrients (e.g., zinc) as well as vitamin B12 have been reported in the elderly, thus accounting for frailty in the host [52, 53]. However, the relationship between oligoelements and vitamin B12 and intestinal microbiota deserves further investigation in elderly.

Conclusion

In conclusion, more studies are needed for a better comprehension of the interplay between human microbiota and gut immune cells in elderly. In fact, inter individual variations of microbiota composition mostly depending on the type of diet, life style as well use of different molecular techniques of bacterial identification seem to represent the major difficulties in this area of research. In this direction, in a very recent editorial Sartor [54] has pointed out the emergence of certain strains of sulphate-reducing Deltaprotobacteria, e.g., Bilophila (B.) wadsworthia, which induces colitis in mice through release of interferon-γ by Th1 cells. Quite interestingly, B. wadsworthia is increased in patients with ulcerative colitis, thus suggesting the need to identify new subsets of patients with IBD using Deltaprotobacteria as biomarkers [55]. It appears that consumption of saturated milk fat led to expansion of B. wadsworthia in mice [55]. Therefore, the possibility that also in humans changes of microbiota could be induced by milk-fat intake should be taken into consideration. On the other hand, in spite of many advances in the field of mucosal immunity, age-related changes, which occur at mucosal surface, are still not completely explored. Most of the present knowledge is related to studies in rodent models, while a few investigations have been conducted on the human aged mucosal immunity. In order to overcome this problem the use of humanized mice may help in the understanding of mucosal immunity in elderly and, for instance, constructing effective vaccines to combat infectious diseases, as well as targeting specific components of the intestinal microbiota with the supplementation of nutraceuticals seem to represent the major therapeutic intervention [56, 57].

Abbreviations

APCs: 

Antigen presenting cells

b240: 

Lactobacillus pentosus strain b240

CRC: 

Colon rectal cancer

DCs: 

Dendritic cells

GALT: 

Gut associated lymphoid tissue

IECs: 

Intestinal epithelial cells

IL: 

Interleukin

IBD: 

Inflammatory bowel disease

LP: 

Lamina propria

M: 

Microfolding cell

NK: 

Natural killer

RA: 

Retinoic acid

SCFA: 

Short chain fatty acids

SFB: 

Segmented filamentous bacteria

sIg: 

Secretory immunoglobulin

TGF: 

Transforming growth factor

Th: 

T helper

TLR: 

Toll-like receptor

Treg: 

T regulatory

TNF: 

Tumor necrosis factor.

Declarations

Acknowledgements

Paper supported in part by an intramural grant (ex 60%) from the University of Bari, Bari, (Italy).

Authors’ Affiliations

(1)
Department of Basic Medical Sciences, Neuroscience and Sensory Organs,, University of Bari,Policlinico,, Bari, Italy

References

  1. Moore WE, Holdeman LV: Human fecal flora: the normal flora of 20 Japanese-Hawaiians. Appl Microbiol. 1974, 27: 961-979.PubMed CentralPubMedGoogle Scholar
  2. Ley RE, Peterson DA, Gordon JI: Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006, 124: 837-848. 10.1016/j.cell.2006.02.017.View ArticlePubMedGoogle Scholar
  3. Ouwehand A, Vesterlund S: Health aspects of probiotics. IDrugs. 2003, 6: 573-580.PubMedGoogle Scholar
  4. Zoetendal EG, von Wright A, Vilpponen-Salmela T, Ben-Amor K, Akkermans AD, de Vos WM: Mucosa-associated bacteria in the human gastrointestinal tract are uniformly distributed along the colon and differ from the community recovered from feces. Appl Environ Microbiol. 2002, 68: 3401-3407. 10.1128/AEM.68.7.3401-3407.2002.PubMed CentralView ArticlePubMedGoogle Scholar
  5. Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA: Diversity of the human intestinal microbial flora. Science. 2005, 308: 1635-1638. 10.1126/science.1110591.PubMed CentralView ArticlePubMedGoogle Scholar
  6. Louis P, Scott KP, Duncan SH, Flint HJ: Understanding the effects of diet on bacterial metabolism in the large intestine. J Appl Microbiol. 2007, 102: 1197-1208. 10.1111/j.1365-2672.2007.03322.x.View ArticlePubMedGoogle Scholar
  7. Miron N, Cristea V: Enterocytes: active cells in tolerance to food and microbial antigens in the gut. Clin Exp Immunol. 2012, 167: 405-412. 10.1111/j.1365-2249.2011.04523.x.PubMed CentralView ArticlePubMedGoogle Scholar
  8. Kraehenbuhl JP, Neutra MR: Epithelial M cells: differentiation and function. Annu Rev Cell Dev Biol. 2000, 16: 301-332. 10.1146/annurev.cellbio.16.1.301.View ArticlePubMedGoogle Scholar
  9. Iwasaki A: Mucosal dendritic cells. Annu Rev Immunol. 2007, 25: 381-418. 10.1146/annurev.immunol.25.022106.141634.View ArticlePubMedGoogle Scholar
  10. Kanai T, Mikami Y, Sujino T, Hisamatsu T, Hibi T: RORγt-dependent IL-17A-producing cells in the pathogenesis of intestinal inflammation. Mucosal Immunol. 2012, 5: 240-247. 10.1038/mi.2012.6.View ArticlePubMedGoogle Scholar
  11. Maldonado RA, von Andrian UH: How tolerogenic dendritic cells induce regulatory T cells. Adv Immunol. 2010, 108: 111-165.PubMed CentralView ArticlePubMedGoogle Scholar
  12. Hadis U, Wahl B, Schulz O, Hardtke-Wolenski M, Schippers A, Wagner N, Müller W, Sparwasser T, Förster R, Pabst O: Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity. 2011, 34: 237-246. 10.1016/j.immuni.2011.01.016.View ArticlePubMedGoogle Scholar
  13. Agace WW, Persson EK: How vitamin A metabolizing dendritic cells are generated in the gut mucosa. Trends Immunol. 2012, 33: 42-48. 10.1016/j.it.2011.10.001.View ArticlePubMedGoogle Scholar
  14. Dicarlo AL, Fuldner R, Kaminski J, Hodes R: Aging in the context of immunological architecture, function and disease outcomes. Trends Immunol. 2009, 30: 293-294. 10.1016/j.it.2009.05.003.View ArticlePubMedGoogle Scholar
  15. Biagi E, Candela M, Turroni S, Garagnani P, Franceschi C, Brigidi P: Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2012, 10.1016/j.phrs.2012.10.005.Google Scholar
  16. Larbi A, Franceschi C, Mazzatti D, Solana R, Wikby A, Pawelec G: Aging of the immune system as a prognostic factor for human longevity. Physiology (Bethesda). 2008, 23: 64-74. 10.1152/physiol.00040.2007.View ArticleGoogle Scholar
  17. Magrone T, Jirillo E: The interplay between the gut immune system and microbiota in health and disease: nutraceutical intervention for restoring intestinal homeostasis. Curr Pharm Des. 2013, 9 (7): 1329-1342.Google Scholar
  18. Round JL, Mazmanian SK: Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A. 2010, 107: 12204-12209. 10.1073/pnas.0909122107.PubMed CentralView ArticlePubMedGoogle Scholar
  19. Davies JM, Sheil B, Shanahan F: Bacterial signalling overrides cytokine signalling and modifies dendritic cell differentiation. Immunology. 2009, 128 (Suppl 1): e805-e815.PubMed CentralView ArticlePubMedGoogle Scholar
  20. Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, Wei D, Goldfarb KC, Santee CA, Lynch SV, Tanoue T, Imaoka A, Itoh K, Takeda K, Umesaki Y, Honda K, Littman DR: Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009, 139: 485-498. 10.1016/j.cell.2009.09.033.PubMed CentralView ArticlePubMedGoogle Scholar
  21. Feng T, Wang L, Schoeb TR, Elson CO, Cong Y: Microbiota innate stimulation is a prerequisite for T cell spontaneous proliferation and induction of experimental colitis. J Exp Med. 2010, 207: 1321-1332. 10.1084/jem.20092253.PubMed CentralView ArticlePubMedGoogle Scholar
  22. Claesson MJ, Cusack S, O'Sullivan O, Greene-Diniz R, de Weerd H, Flannery E, Marchesi JR, Falush D, Dinan T, Fitzgerald G, Stanton C, van Sinderen D, O'Connor M, Harnedy N, O'Connor K, Henry C, O'Mahony D, Fitzgerald AP, Shanahan F, Twomey C, Hill C, Ross RP, O'Toole PW: Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A. 2011, 108 (Suppl 1): 4586-4591.PubMed CentralView ArticlePubMedGoogle Scholar
  23. Hopkins MJ, Sharp R, Macfarlane GT: Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles. Gut. 2001, 48: 198-205. 10.1136/gut.48.2.198.PubMed CentralView ArticlePubMedGoogle Scholar
  24. He T, Harmsen HJ, Raangs GC, Welling GW: Composition of faecal microbiota of elderly people. Microb Ecol Health Dis. 2003, 15: 153-159. 10.1080/08910600310020505.View ArticleGoogle Scholar
  25. Harmsen HJ, Wildeboer-Veloo AC, Grijpstra J, Knol J, Degener JE, Welling GW: Development of 16S rRNA-based probes for the Coriobacterium group and the Atopobium cluster and their application for enumeration of Coriobacteriaceae in human feces from volunteers of different age groups. Appl Environ Microbiol. 2000, 66: 4523-4527. 10.1128/AEM.66.10.4523-4527.2000.PubMed CentralView ArticlePubMedGoogle Scholar
  26. Tiihonen K, Ouwehand AC, Rautonen N: Human intestinal microbiota and healthy ageing. Ageing Res Rev. 2010, 9: 107-116. 10.1016/j.arr.2009.10.004.View ArticlePubMedGoogle Scholar
  27. Biagi E, Nylund L, Candela M, Ostan R, Bucci L, Pini E, Nikkïla J, Monti D, Satokari R, Franceschi C, Brigidi P, De Vos W: Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians. PLoS One. 2010, 5: e10667-10.1371/journal.pone.0010667.PubMed CentralView ArticlePubMedGoogle Scholar
  28. Pédron T, Sansonetti P: Commensals, bacterial pathogens and intestinal inflammation: an intriguing ménage à trois. Cell Host Microbe. 2008, 3: 344-347. 10.1016/j.chom.2008.05.010.View ArticlePubMedGoogle Scholar
  29. De Vuyst L, Leroy F: Cross-feeding between bifidobacteria and butyrate-producing colon bacteria explains bifdobacterial competitiveness, butyrate production, and gas production. Int J Food Microbiol. 2011, 149: 73-80. 10.1016/j.ijfoodmicro.2011.03.003.View ArticlePubMedGoogle Scholar
  30. Ioannidis O, Varnalidis I, Paraskevas G, Botsios D: Nutritional modulation of the inflammatory bowel response. Digestion. 2011, 84: 89-101. 10.1159/000323456.View ArticlePubMedGoogle Scholar
  31. Schiffrin EJ, Morley JE, Donnet-Hughes A, Guigoz Y: The inflammatory status of the elderly: the intestinal contribution. Mutat Res. 2010, 690: 50-56. 10.1016/j.mrfmmm.2009.07.011.View ArticlePubMedGoogle Scholar
  32. Manichanh C, Borruel N, Casellas F, Guarner F: The gut microbiota in IBD. Nat Rev Gastroenterol Hepatol. 2012, 9: 599-608. 10.1038/nrgastro.2012.152.View ArticlePubMedGoogle Scholar
  33. Kraus S, Arber N: Inflammation and colorectal cancer. Curr Opin Pharmacol. 2009, 9: 405-410. 10.1016/j.coph.2009.06.006.View ArticlePubMedGoogle Scholar
  34. Kinross J, Nicholson JK: Gut microbiota: dietary and social modulation of gut microbiota in the elderly. Nat Rev Gastroenterol Hepatol. 2012, 9: 563-564. 10.1038/nrgastro.2012.169.View ArticlePubMedGoogle Scholar
  35. Ley RE, Turnbaugh PJ, Klein S, Gordon JI: Microbial ecology: Human gut microbes associated with obesity. Nature. 2006, 444: 1022-1023. 10.1038/4441022a.View ArticlePubMedGoogle Scholar
  36. Candore G, Caruso C, Jirillo E, Magrone T, Vasto S: Low grade inflammation as a common pathogenetic denominator in age-related diseases: novel drug targets for anti-ageing strategies and successful ageing achievement. Curr Pharm Des. 2010, 16: 584-596. 10.2174/138161210790883868.View ArticlePubMedGoogle Scholar
  37. Roberfroid M, Gibson GR, Hoyles L, McCartney AL, Rastall R, Rowland I, Wolvers D, Watzl B, Szajewska H, Stahl B, Guarner F, Respondek F, Whelan K, Coxam V, Davicco MJ, Léotoing L, Wittrant Y, Delzenne NM, Cani PD, Neyrinck AM, Meheust A: Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010, 104 (Suppl 2): S1-S63.View ArticlePubMedGoogle Scholar
  38. Hume ME: Historic perspective: prebiotics, probiotics, and other alternatives to antibiotics. Poult Sci. 2011, 90: 2663-2669. 10.3382/ps.2010-01030.View ArticlePubMedGoogle Scholar
  39. Wallace TC, Guarner F, Madsen K, Cabana MD, Gibson G, Hentges E, Sanders ME: Human gut microbiota and its relationship to health and disease. Nutr Rev. 2011, 69: 392-403. 10.1111/j.1753-4887.2011.00402.x.View ArticlePubMedGoogle Scholar
  40. de LeBlanc AM, Castillo NA, Perdigon G: Anti-infective mechanisms induced by a probiotic Lactobacillus strain against Salmonella enterica serovar Typhimurium infection. Int J Food Microbiol. 2010, 138: 223-231. 10.1016/j.ijfoodmicro.2010.01.020.View ArticleGoogle Scholar
  41. Macpherson AJ, Slack E: The functional interactions of commensal bacteria with intestinal secretory IgA. Curr Opin Gastroenterol. 2007, 23: 673-678. 10.1097/MOG.0b013e3282f0d012.View ArticlePubMedGoogle Scholar
  42. Kwon HK, Lee CG, So JS, Chae CS, Hwang JS, Sahoo A, Nam JH, Rhee JH, Hwang KC, Im SH: Generation of regulatory dendritic cells and CD4 + Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci U S A. 2010, 107: 2159-2164. 10.1073/pnas.0904055107.PubMed CentralView ArticlePubMedGoogle Scholar
  43. Gill HS, Rutherfurd KJ, Cross ML, Gopal PK: Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr. 2001, 74: 833-839.PubMedGoogle Scholar
  44. Shinkai S, Toba M, Saito T, Sato I, Tsubouchi M, Taira K, Kakumoto K, Inamatsu T, Yoshida H, Fujiwara Y, Fukaya T, Matsumoto T, Tateda K, Yamaguchi K, Kohda N, Kohno S: Immunoprotective effects of oral intake of heat-killed Lactobacillus pentosus strain b240 in elderly adults: a randomised, double-blind, placebo-controlled trial. Br J Nutr. 2012, 1-10. http://dx.doi.org/10.1017/S0007114512003753,Google Scholar
  45. Bartosch S, Woodmansey EJ, Paterson JC, McMurdo ME, Macfarlane GT: Microbiological effects of consuming a synbiotic containing Bifidobacterium bifidum, Bifidobacterium lactis, and oligofructose in elderly persons, determined by real-time polymerase chain reaction and counting of viable bacteria. Clin Infect Dis. 2005, 40: 28-37. 10.1086/426027.View ArticlePubMedGoogle Scholar
  46. Amati L, Marzulli G, Martulli M, Pugliese V, Caruso C, Candore G, Vasto S, Jirillo E: Administration of a synbiotic to free-living elderly and evaluation of serum cytokines. A pilot study. Curr Pharm Des. 2010, 16: 854-858. 10.2174/138161210790883633.View ArticlePubMedGoogle Scholar
  47. Vendrame S, Guglielmetti S, Riso P, Arioli S, Klimis-Zacas D, Porrini M: Six-week consumption of a wild blueberry powder drink increases bifidobacteria in the human gut. J Agric Food Chem. 2011, 59: 12815-12820. 10.1021/jf2028686.View ArticlePubMedGoogle Scholar
  48. Jacobs DM, Deltimple N, van Velzen E, van Dorsten FA, Bingham M, Vaughan EE, van Duynhoven J: (1)H NMR metabolite profiling of feces as a tool to assess the impact of nutrition on the human microbiome. NMR Biomed. 2008, 21: 615-626. 10.1002/nbm.1233.View ArticlePubMedGoogle Scholar
  49. Queipo-Ortuño MI, Boto-Ordóñez M, Murri M, Gomez-Zumaquero JM, Clemente-Postigo M, Estruch R, Cardona Diaz F, Andrés-Lacueva C, Tinahones FJ: Influence of red wine polyphenols and ethanol on the gut microbiota ecology and biochemical biomarkers. Am J Clin Nutr. 2012, 95: 1323-1334. 10.3945/ajcn.111.027847.View ArticlePubMedGoogle Scholar
  50. Magrone T, Marzulli G, Jirillo E: Immunopathogenesis of neurodegenerative diseases: current therapeutic models of neuroprotection with special reference to natural products. Curr Pharm Des. 2012, 18: 34-42. 10.2174/138161212798919057.View ArticlePubMedGoogle Scholar
  51. Kawaguchi K, Matsumoto T, Kumazawa Y: Effects of antioxidant polyphenols on TNF-alpha-related diseases. Curr Top Med Chem. 2011, 11: 1767-1779. 10.2174/156802611796235152.View ArticlePubMedGoogle Scholar
  52. Mocchegiani E, Costarelli L, Giacconi R, Piacenza F, Basso A, Malavolta M: Micronutrient (Zn, Cu, Fe)-gene interactions in ageing and inflammatory age-related diseases: implications for treatments. Ageing Res Rev. 2012, 11: 297-319. 10.1016/j.arr.2012.01.004.View ArticlePubMedGoogle Scholar
  53. Dhonukshe-Rutten RA, Lips M, de Jong N, Chin A, Paw MJ, Hiddink GJ, van Dusseldorp M, De Groot LC, van Staveren WA: Vitamin B-12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men. J Nutr. 2003, 133: 801-807.PubMedGoogle Scholar
  54. Sartor RB: Gut microbiota: Diet promotes dysbiosis and colitis in susceptible hosts. Nat Rev Gastroenterol Hepatol. 2012, 9: 561-562. 10.1038/nrgastro.2012.157.View ArticlePubMedGoogle Scholar
  55. Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, Antonopoulos DA, Jabri B, Chang EB: Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature. 2012, 487: 104-108.PubMed CentralPubMedGoogle Scholar
  56. Fujihashi K, Kiyono H: Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol. 2009, 30: 334-343. 10.1016/j.it.2009.04.004.View ArticlePubMedGoogle Scholar
  57. Rehman T: Role of the gut microbiota in age-related chronic inflammation. Endocr Metab Immune Disord Drug Targets. 2012, 12 (4): 361-367. 10.2174/187153012803832620.View ArticlePubMedGoogle Scholar

Copyright

© Magrone and Jirillo; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement