Cross-feeding between bifidobacteria and butyrate-producing colon bacteria explains bifdobacterial competitiveness, butyrate production, and gas production

Inulin-type fructans are not digested and reach the human colon intact, where they are selectively fermented by the colon microbiota, in particular bifidobacteria. As a result, they are converted, directly or indirectly, to short-chain fatty acids and other organic acids, as well as gases, and lead to both bifidogenic and butyrogenic health-promoting effects. Bifidobacteria display phenotypic variation on strain level as to their capacity to degrade inulin-type fructans. Also, different chain lengths of inulin-type fructans may stimulate different subgroups within the bifidobacterial population. The end-metabolites of inulin-type fructan degradation by bifidobacteria reflect their growth rates on these polymers. Other colon bacteria are also able to degrade inulin-type fructans, as is the case for lactobacilli, Bacteroides, certain enterobacteria, and butyrate producers. Bacterial cross-feeding mechanisms in the colon lay at the basis of overall butyrate production, a functional characteristic of several colon bacteria that is always accompanied by gas production. Finally, specificity of polysaccharide use by the colon microbiota may determine diet-induced alterations in the microbiota and consequent metabolic effects.     

菊粉型果聚糖在无麸质产品中应用的研究进展

由于谷蛋白相关疾病与含谷蛋白食物的摄入有关,无麸质产品在食品工业中受到广泛关注,菊粉型果聚糖已成为无麸质产品的有益成分。本文介绍了菊粉型果聚糖在无麸质产品中应用的技术背景,阐述了菊粉型果聚糖的物理化学特性及其作为组成部分对无麸质产品的技术性能和感官质量的影响,分析了菊粉型果聚糖添加到无麸质产品后与其他成分和添加剂之间的相互作用,旨在为加强无麸质产品的开发及质量提升提供技术参考。     

食品作用于肠黏膜免疫系统可能的信号途径

树突状细胞是体内最强的抗原呈递细胞,也是介导机体先天免疫和获得性免疫的桥梁。当食品中的不同生理活性成分作用于肠黏膜免疫系统时,会被肠黏膜中的树突状细胞吞噬加工呈递,也可以直接结合到DC细胞表面的模式识别受体上,如TLRs、CLRs以及NLRs等,然后启动相应的信号传递途径,从而调节肠黏膜免疫系统中细胞因子网络的变化。本文主要目的是在现有的研究结果的基础上,尽量详尽地判断和揭示食品中的生理活性成分如何与DC相互作用,激发DC可能的信号传导途径,而后如何影响肠黏膜系统中细胞因子的变化。理解这一因果关系,对食品如何发挥其生物功能具有十分重要的指导意义。     

中性大蒜果聚糖体外发酵产短链脂肪酸

大蒜果聚糖是大蒜深加工后废弃蒜渣中的主要成分,不能被人体消化利用,可选择性增殖肠道益生菌,具有开发成新型益生元的潜力。体外发酵产短链脂肪酸的分析对进一步评价大蒜果聚糖对肠道微生态的影响有重要意义。方法:本研究通过体外模拟人体肠道系统的pH、温度和营养条件,接种人体新鲜粪便悬浮液进行间歇式静态厌氧培养,采用高效液相色谱法(HPLC)分析不同聚合度(平均DP为11、16、21)的中性大蒜果聚糖为唯一碳源,培养0、4、8、12、24 h产短链脂肪酸的情况。结果:发酵12 h时短链脂肪酸浓度达到最高,之后便开始下降。其中样a(平均DP为11)的发酵液中总SCFA浓度最高,达86.38μmol/mL。总短链脂肪酸产量为样a(DP 11)>样b(DP16)>样c(DP 21)。24 h时,各发酵液的短链脂肪酸中丁酸和乳酸的比例较乙酸和丙酸高。结论:大蒜果聚糖能被人体肠道微生物发酵利用在体外产短链脂肪酸。其中丁酸和乳酸的摩尔浓度较乙酸和丙酸高。聚合度低的大蒜果聚糖产酸高于聚合度高的果聚糖。     

Significance of Inulin Fructans in the Human Diet

This paper reviews the physicochemical properties and nutritional significance of inulin fructans (oligofructose and inulin). These compounds are naturally present in a large number of food crops and serve in our diet as dietary fiber. Inulin fructans can be isolated and purified from the chicory root and used as ingredients in a large range of foods to improve structure and/or taste and to increase the intake of dietary fiber. Inulin fructans have a low caloric value, are safe, and generally well tolerated up to a level of 20 g/d. They exert a range of effects, which can be differentiated into direct effects on the gut and the intestinal flora and indirect systemic effects. Direct effects on the gut include prebiotic (bifidogenic) effects, improvement of bowel habits and bowel function in constipated subjects, increased colonic absorption of minerals (Ca and Mg), and secretion of satiety hormones. Indirect effects are on blood lipids, bone mineral content, the immune system, and energy homeostasis. These issues are discussed and it is argued that promising avenues for research are particularly in the areas of energy homeostasis and systemic low‐grade inflammation in relation to changes in the composition of the intestinal microbiota.     

Synbiotic Effects of the Dietary Fiber Long‐Chain Inulin and Probiotic Lactobacillus acidophilus W37 Can be Caused by Direct,Synergistic Stimulation of Immune Toll‐Like Receptors and Dendritic Cells

1 Scope

Synbiotic effects of dietary fibers and lactobacilli are usually explained by synergistic modulation of gut microbiota. New insight, however, has demonstrated that both dietary fibers and lactobacilli can directly stimulate immune cells and benefit consumer immunity. Here, the synergistic effects of immune active long‐chain inulin (lcITF) and Lactobacillus acidophilus W37 (LaW37) on dendritic cells (DCs) are investigated.

2 Methods and results

Effects of lcITF and LaW37 alone or combined were studied on Toll‐like receptor (TLRs) signaling and cytokine secretion by DCs in the presence and absence of media of intestinal epithelial cell (IEC) exposed to the ingredients. Also, the effects of DC responses against Salmonella Typhimurium (STM) were investigated. Synergistic effects were observed on TLR2 and 3. Synergistic effects were not always pro‐inflammatory. LaW37 was strongly pro‐inflammatory, while cytokine responses were regulatory when combined with lcITF. Exposure of DCs to IECs medium changed the DCs’ response, which revealed synergistic enhancing effects of lcITF/LaW37 on production of IL‐6 and IL‐8. DCs’ response in the presence of STM and LaW37 were so strong that lcITF had no additional effect.

3 Conclusion

It is demonstrated that synbiotic effects of dietary fibers and bacteria are not limited to the effects on gut microbiota but can also occur by synergistically directly stimulating IECs and/or immune cells.     

Dietary fibres as "prebiotics": implications for colorectal cancer

A "prebiotic" is a nondigestible food ingredient whose beneficial effects on the host result from the selective stimulation of growth and/or activity of members of the bacterial community that inhabits the human bowel (the gut microbiota). Although much of the prebiotic literature focuses on nondigestible oligosaccharides, such as oligofructose, most dietary fibres that are fermentable carbohydrates could be considered as prebiotics. Early studies suggested that colonic bacteria were risk factors for colon cancer. However, altering the composition or metabolic activity of the bowel microbiota through the use of dietary fibre might be important in reducing the prevalence of colorectal cancer. Mechanisms for beneficial effects of prebiotics might include changing the activity of exogenous carcinogens through modulating metabolic activation and/or detoxification, or stimulating the production of the short-chain fatty acid, butyrate. However, modern analytical techniques suggest that an important consequence of a modified bacterial community could be a change in the expression not only of a range of different bacterial genes in bowel contents, but also in the bowel mucosa of the host. Analogous with observations with probiotics, the stimulation of cytokines and modification of immune responses could be important in producing beneficial effects. Compared with transitory effects of probiotics, the prebiotic action of fermentable carbohydrates potentially provide the opportunity for sustainable modulation of activity of the gut microbiota. However, their mechanisms of action in humans are speculative, and research aimed at providing an integrated view of the gut microbiota and dietary fibre nutrition of humans needs to be developed.     

Dietary Amino Acids and the Gut‐Microbiome‐Immune Axis: Physiological Metabolism and Therapeutic Prospects

Dietary amino acids (AAs) are not only absorbed and metabolized by enterocytes but also available to the microbiota in the gut in mammals. In addition to serving as the materials for protein synthesis, AAs can act as precursors for numerous metabolic end products in reactions involving the intestinal mucosa and microbiota. After penetrating the epithelial barrier, microbial metabolites can enter and accumulate in the host circulatory system, where they are sensed by immune cells and then elicit a wide range of biological functions via different receptors and mechanisms. Some intestinal bacteria can also synthesize certain AAs, implying that the exchange of AAs between hosts and microorganisms is bidirectional. Changes in AA composition and abundance can affect AA‐metabolizing bacterial communities and modulate macrophages and dendritic cells via toll‐like receptors (TLRs), autoinducer‐2 (AI‐2), and NOD‐like receptors (NLRs), and also regulate the gut‐microbiome‐immune axis via aryl hydrocarbon receptor (AhR), serotonin/5‐hydroxytryptamine (5‐HT), and other signaling pathways, all of which play critical roles in regulating the intestinal mucosal immunity and microbiota directly or indirectly, contributing to intestinal homeostasis. Therefore, the current findings of the effects of certain functional AAs on the gut‐microbiome‐immune axis are reviewed, illustrating signaling pathways of tryptophan (Trp), glutamine (Gln), methionine (Met), and branched‐chain AAs (BCAAs) in the intestinal barrier and regarding immunity via crosstalk with their receptors or ligands. These findings have shed light on the clinical applications of dietary AAs in improving gut microbiota and mucosal immunity, therefore benefiting the gut as well as local and systemic health.     

Immunomodulating peptides for food allergy prevention and treatment

Among the most promising strategies currently assayed against IgE-mediated allergic diseases stands the possibility of using immunomodulating peptides to induce oral tolerance toward offending food allergens or even to prevent allergic sensitization. This review focuses on the beneficial effects of food derived immunomodulating peptides on food allergy, which can be directly exerted in the intestinal tract or once being absorbed through the intestinal epithelial barrier to interact with immune cells. Food peptides influence intestinal homeostasis by maintaining and reinforcing barrier function or affecting intestinal cell-signalling to nearby immune cells and mucus secretion. In addition, they can stimulate cells of the innate and adaptive immune system while supressing inflammatory responses. Peptides represent an attractive alternative to whole allergens to enhance the safety and efficacy of immunotherapy treatments. The conclusions drawn from curative and preventive experiments in murine models are promising, although there is a need for more pre-clinical studies to further explore the immunomodulating strategy and its mechanisms and for a deeper knowledge of the peptide sequence and structural requirements that determine the immunoregulatory function.     

益生菌活菌与死菌的保健作用研究进展

酸奶和发酵制品均强调活菌的重要性。然而,并非活菌产品才具有保健效果。就乳糖酶缺乏症、过敏性鼻炎、急性胃肠炎患者而言,活菌和死菌具有相似的临床治疗效果。在刺激免疫系统、抗肿瘤、治疗阴道炎等方面,活菌的生理功能强于死菌,而在清除黄曲霉毒素方面,死菌则强于活菌。目前益生菌功能研究多限于活菌,且在某些活菌和死菌功能研究中存在争议,提示将来的研究应对两者进行科学的对照实验。     

The degree of polymerization of inulin-like fructans affects cecal mucin and immunoglobulin A in rats

ABSTRACT:  Cecal amounts of mucin and immunoglobulin A (IgA) were examined through the cecal fermentation pattern in Wistar (WS) or Sprague–Dawley (SD) rats fed inulin-type fructans differing in their degree of polymerization (DP). The animals were fed a control diet or a diet containing one of the fructans with an average DP of 4, 8, 16, or 23, at 60 g/kg diet for 10 d. Cecal fermentation products substantially differed between WS and SD rats fed DP8 fructan, with short-chain fatty acids (SCFAs) as the major organic acids in the former but lactate predominating in the latter. Cecal fermentability of fructans in both strains generally decreased with increasing DP of fructans, and this was especially manifest in reduction of the amounts of lactate in DP16 and 23. In WS rats, cecal mucin and IgA were greater in all fructan groups than in the control group. In SD rats, cecal mucin was greater only in the DP8, 16, and 23 groups as compared to the control group, while IgA was greater in the DP4 and 8 groups. In both strains, cecal mucin correlated with the sum of cecal SCFAs, but not with lactate, succinate, or total organic acids. In contrast, only cecal lactate correlated with cecal IgA in both strains. The present study shows that the different fermentation patterns of fructans affect cecal mucin and IgA; mucin is likely to respond to cecal SCFA production, whereas IgA increases when fermentation occurs rapidly and lactate is a major fermentation product.     

Mucosal immunomodulation by the non-bacterial fraction of milk fermented by Lactobacillus helveticus R389

The health promoting effects ascribed to probiotic bacteria and fermented dairy products arise not only from bacteria themselves but also from metabolites derived from milk fermentation. Exopolysaccharides produced during milk fermentation and peptides derived from major milk proteins, when released during fermentation, are potential modulators of various regulatory processes in the body. The aim of this work was to increase the knowledge of the previously observed immunomodulating capacity of milk fermented by Lactobacillus helveticus R389 by the study of the mucosal immunomodulation exerted by the non-bacterial fraction of the milk fermented at a constant pH6 (NBFpH6). The effects on IL-6 production by small intestine epithelial cells, the profile of IgA+ and cytokine+ cells (IL-2, IL-6, IL-10, TNF-alpha and IFN-gamma) induced in the gut lamina propria, and the levels of total and specific secretory IgA in the lumen of BALB/c mice that received NBFpH6 for 2, 5 or 7 days were examined. There was an increase in the number of IgA+, IL-10+, IL-2+ and IL-6+ cells after all feeding periods. Total S-IgA in the small intestine lumen increased in mice that received NBFpH6 for 2 days. However, no specific antibodies against NBFpH6 were detected. Feeding of NBFpH6 for 7 days significantly (P<0.05) enhanced IL-6 secretion by small intestine epithelial cells. NBFpH6 induced a non-specific mucosal response that was down-regulated for protective immunity, enhancing IL-6 production by epithelial cells and IgA production in the small intestine. These events improve the immunological defenses at the intestinal level, increasing host protection against pathologies. Because mucosal immune responses induced by certain dietary antigens play a large part in the prevention of gastrointestinal diseases, the oral administration of a mucosal adjuvant such as NBFpH6 may positively affect the milieu of the intestinal lumen. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health condition of the host.     

Importance of the host specificity in the selection of probiotic bacteria

The gastrointestinal tract is a complex and dynamic ecosystem. Commensal microorganisms (C), which proliferate in the intestine from birth, are crucial for gut homeostasis while non commensal (NC) microorganisms are transient and enter the organism from the environment and foods. We studied comparatively the influence of oral administration of C and NC Lactobacillus fermentum and Lactobacilus acidophilus on the gut-associated lymphoid tissue (GALT) of conventional mice. To determine the importance of the selection of probiotic host-specificity bacteria with immunomodulating capacity, we examined the interaction with the gut by transmission electron microscopy and FITC-labelled bacteria. We compared the immunomodulation capacities of C and NC strains by studying the number of IgA secreting cells and cytokine profile. No differences were found in the number of IgA+ cells; however, the pattern of cytokine response to C and NC bacteria was different. With regard to proinflammatory cytokine (IFNgamma and TNFalpha), we found that TNFalpha was mainly produced by NC bacteria, while C bacteria were able to elicit mainly IFNgamma. The regulatory cytokines (IL-10 and IL-4) were induced with different patterns for both C and NC strains. No differences in the pathway of internalization to the gut between C and NC were found. In summary, we determined that C and NC bacteria interact with the intestine in the same way; both C and NC bacteria were able to reinforce the surveillance of the gut mucosal immune system. The cytokine profile showed that C bacteria would be involved in the regulation of intestinal homeostasis rather than in the immune activation as the NC bacteria.     

Effects of the oral administration of the products derived from milk fermentation by kefir microflora on immune stimulation

Nutritional status has a major impact on the immune system. Probiotic effects ascribed to fermented dairy products arise not only from whole microorganisms but also from metabolites (peptides, exopolysaccharides) produced during the fermentation. We recently demonstrated the immunomodulating capacity of kefir in a murine model. We now aimed at studying the immunomodulating capacity in vivo of the products derived from milk fermentation by kefir microflora (PMFKM) on the gut. BALB/c mice received the PMFKM for 2, 5 or 7 consecutive days. IgA+ and IgG+ cells were determined on histological slices of the small and large intestine. IL-4, IL-6, IL-10, IL-12, IFNgamma and TNFalpha were determined in the gut, intestinal fluid and blood serum. IL-6 was also determined in the supernatant of a primary culture of small intestine epithelial cells challenged with PMFKM. PMFKM up-regulated IL-6 secretion, necessary for B-cell terminal differentiation to IgA secreting cells in the gut lamina propria. There was an increase in the number of IgA+ cells in the small and large intestine. The increase in the number of IgA+ cells was accompanied by an increase in the number of IL-4+, IL-10+ and IL-6+ cells in the small intestine. Effects of PMFKM in the large intestine were less widely apparent than the ones observed at the small intestine lamina propria. All cytokines that increased in the small intestine lamina propria, also did so in blood serum, reflecting here the immunostimulation achieved in the gut mucosa. We observed that the PMFKM induced a mucosal response and it was able to up and down regulate it for protective immunity, maintaining the intestinal homeostasis, enhancing the IgA production at both the small and large intestine level. The opportunity exists then to manipulate the constituents of the lumen of the intestine through dietary means, thereby enhancing the health status of the host.     

Nondigestible carbohydrates,butyrate, and butyrate-producing bacteria

Abstract

Nondigestible carbohydrates (NDCs) are fermentation substrates in the colon after escaping digestion in the upper gastrointestinal tract. Among NDCs, resistant starch is not hydrolyzed by pancreatic amylases but can be degraded by enzymes produced by large intestinal bacteria, including clostridia, bacteroides, and bifidobacteria. Nonstarch polysaccharides, such as pectin, guar gum, alginate, arabinoxylan, and inulin fructans, and nondigestible oligosaccharides and their derivatives, can also be fermented by beneficial bacteria in the large intestine. Butyrate is one of the most important metabolites produced through gastrointestinal microbial fermentation and functions as a major energy source for colonocytes by directly affecting the growth and differentiation of colonocytes. Moreover, butyrate has various physiological effects, including enhancement of intestinal barrier function and mucosal immunity. In this review, several representative NDCs are introduced, and their chemical components, structures, and physiological functions, including promotion of the proliferation of butyrate-producing bacteria and enhancement of butyrate production, are discussed. We also describe the strategies for achieving directional accumulation of colonic butyrate based on endogenous generation mechanisms.     

原花青素生理功能及其与肠道微生物相互作用的研究进展

近年来,以原花青素(proanthocyanidins,PACs)为代表的一大类天然来源的多酚化合物,被证实兼有抗氧化、抗菌抗炎、抗肿瘤和防控心血管疾病及代谢综合征等生理功能,在人类健康防控中发挥重要作用。生物利用度不佳是阻碍PACs广泛应用的关键问题,亟待解决。虽然PACs与微生物相互作用的研究尚不多见,但已有研究指出肠道微生物表现出促进PACs分解代谢、提高其生物活性、改善生物利用度等积极作用,且PACs可促进肠道有益菌生长、抑制肠道有害菌而发挥出良好的肠道菌群的调节作用。二者间的双向调节作用也在各类常见代谢疾病中表现出潜在应用价值,研究前景良好。本文旨在比较PACs与花青素的异同点、归纳PACs的生理功能、综述其与肠道微生物尤其是乳酸菌、双歧杆菌等的相互作用,以期为人体健康潜在影响物质的研究提供理论参考。     

肠源性短链脂肪酸生成机制及其饮食调控

短链脂肪酸(short chain fatty acids, SCFAs)作为肠道微生物的重要代谢产物,将宿主饮食与肠道微生物之间复杂的相互作用关系有机地联系在一起。SCFAs是近年来微生物代谢产物与人体健康科研领域研究热点,SCFAs不仅作为肠道上皮细胞的重要能源物质,也是游离脂肪酸受体的天然配体,因此发挥着多种健康作用,如调节脂质代谢、免疫、炎症反应和食欲等。阐述了肠源性SCFAs前体物质的主要食物来源,详细探讨了参与SCFAs生成的肠道微生物及代谢途径,并提出了肠源性SCFAs的饮食调控策略。从化学结构上看,SCFAs是一类碳原子数小于7的挥发性有机酸,肠源性SCFAs主要包括乙酸、丙酸、丁酸,它们主要是由SCFAs前体物质在肠道菌群的酵解作用下转化生成。SCFAs前体物质的食物来源多种多样,不易消化的碳水化合物是SCFAs的主要食物前体,包含抗性淀粉、非淀粉多糖、低聚糖等。肠道中的多种微生物能够通过不同代谢途径独立或者协同利用SCFAs前体物质产生SCFAs。补充富含SCFAs前体物质的食物,不仅能够影响肠源性SCFAs的含量,还可选择性地促进肠道中有益菌的生长,从质和量上维护肠道微生态稳态、直接或者间接地调节机体多种生理功能,促进人体健康功能。希望可为预防和治疗相关代谢和免疫疾病提供新的思路。     

益生乳酸菌与肠道菌群稳态

肠道是个复杂的微生态系统,不仅包含宿主细胞和各种营养物质,还包含数以万计的微生物。这些肠道微生物与宿主健康息息相关,对宿主营养、代谢、生理和免疫均有影响,肠道菌群发生紊乱还会引起各种疾病。大量临床试验表明,益生乳酸菌可通过调节宿主肠道菌群稳态治疗或缓解多种疾病。本文作者描述了失衡指数（DI）、微生物平衡指数（MBI）和微生物失衡指数（MDI）这3种量化肠道菌群稳态的计算方法及其应用,阐述了益生乳酸菌对肥胖和健康宿主肠道菌群稳态的影响,指出益生乳酸菌可能通过与肠道中病原菌竞争结合位点或分泌物质抑制病原菌,分泌代谢物为肠道中有益共生菌提供适宜生长繁殖的环境和制造“假想敌”刺激宿主免疫系统应答等方式维持宿主肠道菌群稳态,并讨论了维持宿主肠道菌群稳态的重要性。同时还综述了益生乳酸菌研究现状,指出益生乳酸菌的研究要做到个性化,不仅要考虑研究人群个体差异,还要考虑菌株之间的差异。     

Modulation of Intestinal Epithelial Defense Responses by Probiotic Bacteria

Probiotics are live microorganisms, which when administered in food confer numerous health benefits. In previous studies about beneficial effects of probiotic bacteria to health, particularly in the fields of intestinal mucosa defense responses, specific probiotics, in a strain-dependent manner, show certain degree of potential to reinforce the integrity of intestinal epithelium and/or regulate some immune components. The mechanism of probiotic action is an area of interest. Among all possible routes of modulation by probiotics of intestinal epithelial cell-mediated defense responses, modulations of intestinal barrier function, innate, and adaptive mucosal immune responses, as well as signaling pathways are considered to play important role in the intestinal defense responses against pathogenic bacteria. This review summarizes the beneficial effects of probiotic bacteria to intestinal health together with the mechanisms affected by probiotic bacteria: barrier function, innate, and adaptive defense responses such as secretion of mucins, defensins, trefoil factors, immunoglobulin A (IgA), Toll-like receptors (TLRs), cytokines, gut associated lymphoid tissues, and signaling pathways.     

Iron bioavailability from ferric pyrophosphate in rats fed with fructan-containing yacon (Smallanthus sonchifolius) flour

The effects of inulin-type fructans (ITF)-containing yacon flour (YF) on Fe bioavailability from ferric pyrophosphate (FP) were evaluated in Fe-deficient rats using the Hb repletion efficiency (HRE) assay. Weanling male Wistar rats were fed a low-Fe diet (12 mg/kg) for 15 days followed by 2 weeks of Fe repletion with diets providing 35 mg Fe/kg as either ferrous sulphate (FS) or FP, supplemented with 7.5% ITF as either YF or Raftilose (RAF), a purified ITF. ITF increased caecal fermentation, whereas YF was more butyrogenic than RAF. ITF improved HRE in FP-fed rats, and those fed YF had a higher relative biological value compared with those fed FP and RAF. Liver Fe was increased by ITF, but only YF led to values similar to those in the FS group. It is observed that ITF increased caecal fermentation and Fe bioavailability. These effects were more pronounced when YF was the ITF source.