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      Intestinal microbiota, probiotics and mental health: from Metchnikoff to modern advances: Part II – contemporary contextual research

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          Abstract

          In recent years there has been a renewed interest concerning the ways in which the gastrointestinal tract – its functional integrity and microbial residents – might influence human mood (e.g. depression) and behavioral disorders. Once a hotbed of scientific interest in the early 20th century, this area lay dormant for decades, in part due to its association with the controversial term ‘autointoxication’. Here we review contemporary findings related to intestinal permeability, small intestinal bacterial overgrowth, lipopolysaccharide endotoxin (LPS) exposure, D-lactic acid, propionic acid, and discuss their relevance to microbiota and mental health. In addition, we include the context of modern dietary habits as they relate to depression, anxiety and their potential interaction with intestinal microbiota.

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          Increased Gut Permeability and Microbiota Change Associate with Mesenteric Fat Inflammation and Metabolic Dysfunction in Diet-Induced Obese Mice

          Yan Lam, Connie Ha, Craig Campbell … (2012)
          We investigated the relationship between gut health, visceral fat dysfunction and metabolic disorders in diet-induced obesity. C57BL/6J mice were fed control or high saturated fat diet (HFD). Circulating glucose, insulin and inflammatory markers were measured. Proximal colon barrier function was assessed by measuring transepithelial resistance and mRNA expression of tight-junction proteins. Gut microbiota profile was determined by 16S rDNA pyrosequencing. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 mRNA levels were measured in proximal colon, adipose tissue and liver using RT-qPCR. Adipose macrophage infiltration (F4/80+) was assessed using immunohistochemical staining. HFD mice had a higher insulin/glucose ratio (P = 0.020) and serum levels of serum amyloid A3 (131%; P = 0.008) but reduced circulating adiponectin (64%; P = 0.011). In proximal colon of HFD mice compared to mice fed the control diet, transepithelial resistance and mRNA expression of zona occludens 1 were reduced by 38% (P<0.001) and 40% (P = 0.025) respectively and TNF-α mRNA level was 6.6-fold higher (P = 0.037). HFD reduced Lactobacillus (75%; P<0.001) but increased Oscillibacter (279%; P = 0.004) in fecal microbiota. Correlations were found between abundances of Lactobacillus (r = 0.52; P = 0.013) and Oscillibacter (r = −0.55; P = 0.007) with transepithelial resistance of the proximal colon. HFD increased macrophage infiltration (58%; P = 0.020), TNF-α (2.5-fold, P<0.001) and IL-6 mRNA levels (2.5-fold; P = 0.008) in mesenteric fat. Increased macrophage infiltration in epididymal fat was also observed with HFD feeding (71%; P = 0.006) but neither TNF-α nor IL-6 was altered. Perirenal and subcutaneous adipose tissue showed no signs of inflammation in HFD mice. The current results implicate gut dysfunction, and attendant inflammation of contiguous adipose, as salient features of the metabolic dysregulation of diet-induced obesity.
          Article 0 comments Cited 259 times – based on 0 reviews     Review now
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            Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study.

            Jelena Vulevic, Catherine Kwik-Uribe, Xenofon Tzounis … (2010)
            The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota. We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study. Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured. Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P < 0.01) and lactobacilli (P < 0.001) populations but significantly decreased clostridia counts (P < 0.001). These microbial changes were paralleled by significant reductions in plasma triacylglycerol (P < 0.05) and C-reactive protein (P < 0.05) concentrations. Furthermore, changes in C-reactive protein concentrations were linked to changes in lactobacilli counts (P < 0.05, R(2) = -0.33 for the model). These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments. This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods. This trial was registered at clinicaltrials.gov as NCT01091922.
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              Antibiotics protect against fructose-induced hepatic lipid accumulation in mice: role of endotoxin.

              Ina Bergheim, Synia Weber, Miriam B Vos … (2008)
              Consumption of refined carbohydrates in soft drinks has been postulated to be a key factor in the development of non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to test the effects of ad libitum access to different sugars consumed in drinking water on hepatic fat accumulation. For 8 weeks, C57BL/J6 mice had free access to solutions containing 30% glucose, fructose, sucrose, or water sweetened with artificial sweetener (AS) or plain water. Body weight, caloric intake, hepatic steatosis and lipid peroxidation were assessed. Total caloric intake and weight gain were highest in mice exposed to glucose. In contrast, hepatic lipid accumulation was significantly higher in mice consuming fructose compared to all other groups. Moreover, endotoxin levels in portal blood and lipid peroxidation as well as TNFalpha expression were significantly higher in fructose fed mice than in all other groups. Concomitant treatment of fructose fed mice with antibiotics (e.g., polymyxin B and neomycin) markedly reduced hepatic lipid accumulation in fructose fed mice. These data support the hypothesis that high fructose consumption may not only lead to liver damage through overfeeding but also may be directly pro-inflammatory by increasing intestinal translocation of endotoxin.
              Article 0 comments Cited 181 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Alison C Bested
                Alan C Logan
                Eva M Selhub
                Journal
                Journal ID (nlm-ta): Gut Pathog
                Journal ID (iso-abbrev): Gut Pathog
                Title: Gut Pathogens
                Publisher: BioMed Central
                ISSN (Electronic): 1757-4749
                Publication date Collection: 2013
                Publication date (Electronic): 14 March 2013
                Volume: 5
                Page: 3
                Affiliations
                [1 ]Complex Chronic Diseases Program, BC Women's Hospital and Health Centre, B223A-4500 Oak Street, Vancouver, BC V6H 3N1, Canada
                [2 ]CAMNR, 775 Blithedale Avenue, Suite 364, Mill Valley, CA 94941, USA
                [3 ]Harvard Medical School and Massachusetts General Hospital, 40 Crescent St., Suite 201, Waltham, MA 02453, USA
                Article
                Publisher ID: 1757-4749-5-3
                DOI: 10.1186/1757-4749-5-3
                PMC ID: 3601973
                PubMed ID: 23497633
                SO-VID: 2f3b5d5a-c90f-421b-8e78-8eaff20af6d4
                Copyright © Copyright ©2013 Bested et al; licensee BioMed Central Ltd.
                License:

                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.

                History
                Date received : 7 February 2013
                Date accepted : 10 March 2013
                Categories
                Subject: Review

                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: intestinal microbiota,autointoxication,depression,anxiety,probiotics,microbial ecology,lipopolysaccharide endotoxin,diet,intestinal permeability,microbial ecosystems
                Data availability:
                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: intestinal microbiota, autointoxication, depression, anxiety, probiotics, microbial ecology, lipopolysaccharide endotoxin, diet, intestinal permeability, microbial ecosystems

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