Human Large Bowel Research Articles

Haustral rhythmic motor patterns of the human large bowel revealed by ultrasound.

Effective and widely available strategies are needed to diagnose colonic motility dysfunction. We investigated whether ultrasonography could generate spatiotemporal maps combined with motor pattern frequency analysis, to become a noninvasive method to characterize human colon motor patterns. Abdominal colonic ultrasonography was performed on healthy subjects (N = 7), focusing on the detailed recording of spontaneous haustral activities. We developed image segmentation and frequency analysis software to analyze the motor patterns captured. Ultrasonography recordings of the ascending, transverse, and descending colon identified three distinct rhythmic motor patterns: the 1 cycle/min and the 3 cycles/min cyclic motor pattern were seen throughout the whole colon, whereas the 12 cycles/min cyclic motor pattern was identified in the ascending colon. The rhythmic motor patterns of the human colon that are associated with interstitial cells of Cajal-associated pacemaking activity can be accurately identified and quantified using ultrasound.NEW & NOTEWORTHY Ultrasonography in the clinical field is an underutilized tool for assessing colonic motility; however, with the addition of frequency analysis techniques, it provides a method to identify human colonic motor patterns. Here we report on the 1, 3, and 12 cpm rhythmic motor patterns. Ultrasound has the potential to become a bedside assessment for colonic dysmotility and may reveal the health of interstitial cells of Cajal (ICC) pacemaker activities.

Characterisation of parasympathetic ascending nerves in human colon.

In the human large bowel, sacral parasympathetic nerves arise from S2 to S4, project to the pelvic plexus ("hypogastric plexus") and have post-ganglionic axons entering the large bowel near the rectosigmoid junction. They then run long distances orally or aborally within the bowel wall forming "ascending nerves" or "shunt fascicles" running in the plane of the myenteric plexus. They form bundles of nerve fibres that can be distinguished from the myenteric plexus by their straight orientation, tendency not to merge with myenteric ganglia and greater width. To identify reliable marker(s) to distinguish these bundles of ascending nerves from other extrinsic and intrinsic nerves in human colon. Human colonic segments were obtained with informed consent, from adult patients undergoing elective surgery (n = 21). Multi-layer immunohistochemical labelling with neurofilament-H (NF200), myelin basic protein (MBP), von Willebrand factor (vWF), and glucose transporter 1 (GLUT1), and rapid anterograde tracing with biotinamide, were used to compare ascending nerves and lumbar colonic nerves. The rectosigmoid and rectal specimens had 6-11 ascending nerves spaced around their circumference. Distal colon specimens typically had 1-3 ascending nerves, with one located near the mesenteric taenia coli. No ascending nerves were observed in ascending colon specimens. GLUT1 antisera labelled both sympathetic lumbar colonic nerves and ascending nerves in the gut wall. Lumbar colonic nerves joined the myenteric plexus and quickly lost GLUT1 labelling, whereas GLUT1 staining labelled parasympathetic ascending nerves over many centimetres. Ascending nerves can be distinguished in the colorectum of humans using GLUT1 labelling combined with NF200.

Natural Merosesquiterpenes Activate the DNA Damage Response via DNA Strand Break Formation and Trigger Apoptotic Cell Death in p53-Wild-type and Mutant Colorectal Cancer.

Simple SummaryBowel cancer is a serious disease, which affects many people worldwide. Unfortunately, the disease is often diagnosed in an advanced stage, which impairs the chance of survival. Furthermore, resistance to therapy occurs frequently. Thus, novel therapeutic approaches are required to improve cancer therapy. Here, we studied whether merosesquiterpenes might be useful for cancer treatment. These compounds occur in marine sponges and were isolated by our group. We were able to identify three compounds with potent cytotoxic activity in different cell lines established from human large bowel cancer. Our experiments provided evidence that the compounds cause DNA damage and trigger cell death, so-called mitochondrial apoptosis, which was attested in cancer cells with expression of wild-type and mutated p53 tumor suppressor. Finally, we show that merosesquiterpenes also kill intestinal tumor organoids, an ex vivo model of large bowel cancer.Colorectal cancer (CRC) is a frequently occurring malignant disease with still low survival rates, highlighting the need for novel therapeutics. Merosesquiterpenes are secondary metabolites from marine sponges, which might be useful as antitumor agents. To address this issue, we made use of a compound library comprising 11 isolated merosesquiterpenes. The most cytotoxic compounds were smenospongine > ilimaquinone ≈ dactylospontriol, as shown in different human CRC cell lines. Alkaline Comet assays and γH2AX immunofluorescence microscopy demonstrated DNA strand break formation in CRC cells. Western blot analysis revealed an activation of the DNA damage response with CHK1 phosphorylation, stabilization of p53 and p21, which occurred both in CRC cells with p53 knockout and in p53-mutated CRC cells. This resulted in cell cycle arrest followed by a strong increase in the subG1 population, indicative of apoptosis, and typical morphological alterations. In consistency, cell death measurements showed apoptosis following exposure to merosesquiterpenes. Gene expression studies and analysis of caspase cleavage revealed mitochondrial apoptosis via BAX, BIM, and caspase-9 as the main cell death pathway. Interestingly, the compounds were equally effective in p53-wild-type and p53-mutant CRC cells. Finally, the cytotoxic activity of the merosesquiterpenes was corroborated in intestinal tumor organoids, emphasizing their potential for CRC chemotherapy.

NADPH oxidase 1 is highly expressed in human large and small bowel cancers.

To facilitate functional investigation of the role of NADPH oxidase 1 (NOX1) and associated reactive oxygen species in cancer cell signaling, we report herein the development and characterization of a novel mouse monoclonal antibody that specifically recognizes the C-terminal region of the NOX1 protein. The antibody was validated in stable NOX1 overexpression and knockout systems, and demonstrates wide applicability for Western blot analysis, confocal microscopy, flow cytometry, and immunohistochemistry. We employed our NOX1 antibody to characterize NOX1 expression in a panel of 30 human colorectal cancer cell lines, and correlated protein expression with NOX1 mRNA expression and superoxide production in a subset of these cells. Although a significant correlation between oncogenic RAS status and NOX1 mRNA levels could not be demonstrated in colon cancer cell lines, RAS mutational status did correlate with NOX1 expression in human colon cancer surgical specimens. Immunohistochemical analysis of a comprehensive set of tissue microarrays comprising over 1,200 formalin-fixed, paraffin-embedded tissue cores from human epithelial tumors and inflammatory disease confirmed that NOX1 is overexpressed in human colon and small intestinal adenocarcinomas, as well as adenomatous polyps, compared to adjacent, uninvolved intestinal mucosae. In contradistinction to prior studies, we did not find evidence of NOX1 overexpression at the protein level in tumors versus histologically normal tissues in prostate, lung, ovarian, or breast carcinomas. This study constitutes the most comprehensive histopathological characterization of NOX1 to date in cellular models of colon cancer and in normal and malignant human tissues using a thoroughly evaluated monoclonal antibody. It also further establishes NOX1 as a clinically relevant therapeutic target in colorectal and small intestinal cancer.

Seaweed and seaweed-derived metabolites as prebiotics.

Seaweeds and their bioactive compounds, particularly polysaccharides and phenolics can be regarded as great dietary supplements with gut health benefits and prebiotics. These components are resistant to digestion by enzymes present in the human gastrointestinal tract, also selectively stimulate the growth of beneficial gut bacteria and the production of fermentation products such as short chain fatty acids. Commonly, the health benefits of seaweed components are assessed by including them in an in vitro anaerobic fermentation system containing human fecal inocula that mimics the environment of the human large bowel. Regarding to the complex interactions between dietary components, gastrointestinal physiological processes, and gut microbiota are difficult to model in vitro. Consequently it is important to follow up the promising in vitro results with in vivo animal or human testing. The aim of this chapter is to have a comprehensive review on the application of seaweeds and seaweed-derived metabolites as prebiotics, and understand the trends, gaps and future directions of both scientific and industrial developments. This work contributes to develop and expand new platform of seaweed utilization for higher-value products, particularly to functional food and nutraceutical industries in order to serve the social demand for health awareness and support economic development.

Artificial simulation of salivary and gastrointestinal digestion, and fermentation by human fecal microbiota, of polysaccharides from Dendrobium aphyllum.

In vitro salivary and gastrointestinal (GI) digestion and fermentation of polysaccharides extracted from Dendrobium aphyllum were investigated in this study. Salivary amylase showed no influence on D. aphyllum polysaccharides (DAP). The molecular weight of DAP decreased dramatically during the first 0.5 h of gastric digestion, and then reduced steadily during the subsequent GI tract consumption. The content of reducing sugars increased steadily during GI digestion. Only released free mannose of DAP was detectable by gas chromatography-mass spectrometry analysis during the first 12 h of fermentation, which was contributed by fecal microbiota metabolism. In terms of the fermentation pattern, the pH dropped significantly due to the formation of six types of short-chain fatty acids (SCFAs). This study demonstrates that polysaccharides extracted from D. aphyllum can be digested by the GI tract and are physiologically active in the human large bowel by lowering the pH of the large intestinal environment and promoting the production of SCFAs.

Targeted delivery of short-chain fatty acids to the human large bowel

Targeted delivery of short-chain fatty acids to the human large bowel

Human Gut Bacteroidetes

The human large bowel is colonized by a community of microbes, the microbiota, which has a significant impact on human health and nutrition through the production of short chain fatty acids (SCFAs), and by interaction with the host immune system. The major nutrients available to these organisms are dietary glycans, also known as complex carbohydrates. Thus, dietary and nutraceutical strategies, based on complex carbohydrates, can, potentially, be deployed to encourage the dominance of beneficial microbes in the microbiota, particularly those producing health promoting SCFAs such as propionate and butyrate, and bacteria that have an anti‐inflammatory impact through its interaction with the human immune system, ensuring that this microbial ecosystem has a positive influence on human health. This approach, however, is greatly restricted by a critical lack of understanding of the mechanisms by which complex glycans are metabolized by the microbiota. Significantly, the wealth of genomic and metagenomic microbiota sequence presents an exciting, but so far unfulfilled, opportunity to make decisive advances in our understanding of glycan metabolism in the human large bowel. This seminar will review our biochemical, genetic and microbiological strategies, in harness with metagenomic and genomic data, to understand the mechanisms of complex glycans utilization by the human microbiota1,2,3. The models established, will trigger the development of novel dietary strategies that are designed to maximize human health through manipulation of microbiota structure.

Heat shock protein 60 levels in tissue and circulating exosomes in human large bowel cancer before and after ablative surgery.

Heat shock protein 60 (Hsp60) is a chaperonin involved in tumorigenesis, but its participation in tumor development and progression is not well understood and its value as a tumor biomarker has not been fully elucidated. In the current study, the authors presented evidence supporting the theory that Hsp60 has potential as a biomarker as well as a therapeutic target in patients with large bowel cancer. The authors studied a population of 97 subjects, including patients and controls. Immunomorphology, Western blot analysis, and quantitative real-time polymerase chain reaction were performed on tissue specimens. Exosomes were isolated from blood and characterized by electron microscopy, biochemical tests, and Western blot analysis. Hsp60 was found to be increased in cancerous tissue, in which it was localized in the tumor cell plasma membrane, and in the interstitium associated with cells of the immune system, in which it was associated with exosomes liberated by tumor cells and, as such, circulated in the blood. An interesting finding was that these parameters returned to normal shortly after tumor removal. The data from the current study suggested that Hsp60 is a good candidate for theranostics applied to patients with large bowel carcinoma and encourage similar research among patients with other tumors in which Hsp60 has been implicated.

Endocuff-assisted colonoscopy increases polyp detection rate: a simulated randomized study involving an anatomic colorectal model and 32 international endoscopists.

The undetected colonic lesions behind the folds and flexures are a major factor contributing to the adenoma miss rate. To assess the efficacy of Endocuff, a special attachment was fixed at the distal tip of a colonoscope, for the polyp detection. This soft accessory is composed of a plastic cap surrounded by flexible finger-like projections on the lateral sides of the cap that make holding of the folds during scope withdrawal easier. This was a simulated pilot study with one anatomic colorectal model, containing 13 polyps positioned in obvious locations and behind the folds. Thirty-two endoscopists (16 Japanese and 16 foreign visitors) with different levels of experience performed examinations on the model in a randomized order by using Endocuff-assisted colonoscopy (EAC) and standard colonoscope (SC). To assess the detection rate of polyps and the feasibility of Endocuff insertion. EAC detected significantly more polyps than SC with 9.9 versus 7.5 mean lesions (p = 0.03), respectively, comparing the 16 first colonoscopies in each group. Endocuff was useful independent of the level of experience of the participants. After crossover, EAC in second position allowed an additional detection of 1.8 polyps compared with SC (p = 0.001). After adjustment on experience, time of detection, and order of colonoscopy, EAC over-detected 1.2 polyps (p = 0.0037). The insertion time (p = 0.99) was identical. There was no difference in the mean time of polyp detection between EAC and SC groups (p = 0.520). This was not a clinical study. The stiffness of the folds in the colonic model was higher than in the human large bowel. EAC was associated with a higher polyp detection rate. Even in such relatively stiff anatomic model, it was easier to spread out the colonic mucosa between the folds using this cap. This study provides an additional argument for the routine application of this easy-to-use accessory to improve polyp detection.

Dysbiosis in the inflamed intestine

The bacterial microbiota of the human large bowel is a complex ecosystem consisting of several hundred, mostly anaerobic, species. To maintain colonization of the gut lumen and maximize growth in the presence of nutritional competitors, highly diverse metabolic pathways have evolved, with each microbe utilizing a different “winning strategy” for nutrient acquisition and utilization. Conditions and diseases leading to intestinal inflammation are accompanied by a severe disruption the microbiota composition characterized by an expansion of facultative anaerobic Enterobacteriaceae. Here, we review evidence that the local inflammatory response creates a unique nutritional environment that is conducive to a bloom of bacterial species whose genomes encode the capability of utilizing inflammation-derived nutrients.

In vitro fermentation of polysaccharide from the seeds of Plantago asiatica L. by human fecal microbiota

In vitro fermentation of the polysaccharide (PLCP, Mw = 1.90 × 106 Da) from seeds of Plantago asiatica L. and the contribution of its carbohydrates to the fermentation was investigated in this study. The polysaccharide was characterized by high contents of xylose, arabinose and glucuronic acid, and it was subjected to human fecal cultures to be fermented in vitro for 24 h. During fermentation, pH in fecal cultures decreased from 6.1 to 5.1 and the levels of total short-chain fatty acid (SCFA), acetic, propionic and n-butyric acids all significantly increased. Xylanase, arabinofuranosidase, xylosidase and glucuronidase activities were also improved. After 24 h incubation, 47.2 ± 1.6% of total carbohydrate in polysaccharide, including 42.9 ± 1.5% of arabinose, 53.2 ± 1.6% of xylose and 76.4 ± 1.2% of glucuronic acid, were consumed. In addition, relationship between carbohydrate consumption of the polysaccharide and SCFA production was also evaluated. It was found that the increase of acetic and n-butyric acid productions mainly resulted from the fermentation of glucuronic acid and xylose in polysaccharide, while the increase of propionic acid production was primarily due to the fermentation of arabinose and xylose. These results showed that the polysaccharide was physiologically active for human large bowel, and its carbohydrate composition determined its SCFA production.

Promotional Role of Lymphoid Nodules in Colorectal Cancer: Implications for Endoscopic Screening and Prevention

This report examines the anatomical distribution of colorectal cancer CRC in the human large bowel. The find- ings indicate the high occurrence of cancer in the rectum. The reason for the high incidence of rectal cancer is explored. Published data were compiled and analyzed to correlate the high occurrence of CRC in the human rectum to the high oc- currence of lymphoid nodules (LNs). Histopathologic classification and distribution of CRC types was reviewed. Statisti- cal findings reveal a significant (p < 0.01) positive relationship between number of LNs and number of CRCs. Histopa- thological findings indicate that LNs promote epithelial hyperplasia and a nonpolyploid pathway of cancer development especially in the rectum.The findings of a 7 to 8 fold higher density of rectal cancer per cm length in the human rectum compared to the other segments of the large bowel emphasize the importance of careful endoscope screening for the de- tection of nonpolyploid rectal cancers. Review of human and rat literature suggests that drugs that suppress the immune system and that aspirin, an anti-inflammatory agent,may work to reduce risk of CRC via their effect on lymphoid nodules.

Expression pattern, ethanol-metabolizing activities, and cellular localization of alcohol and aldehyde dehydrogenases in human large bowel: association of the functional polymorphisms of ADH and ALDH genes with hemorrhoids and colorectal cancer

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol. Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. The goal of this study was to systematically determine the functional expressions and cellular localization of ADHs and ALDHs in human rectal mucosa, the lesions of adenocarcinoma and hemorrhoid, and the genetic association of allelic variations of ADH and ALDH with large bowel disorders. Twenty-one surgical specimens of rectal adenocarcinoma and the adjacent normal mucosa, including 16 paired tissues of rectal tumor, normal mucosae of rectum and sigmoid colon from the same individuals, and 18 surgical mixed hemorrhoid specimens and leukocyte DNA samples from 103 colorectal cancer patients, 67 hemorrhoid patients, and 545 control subjects recruited in previous study, were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing and the activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies; the cellular activity and protein localizations were detected by immunohistochemistry and histochemistry, respectively. Genotypes of ADH1B, ADH1C, and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphisms. At 33 mM ethanol, pH 7.5, the activity of ADH1C*1/1 phenotypes exhibited 87% higher than that of the ADH1C*1/*2 phenotypes in normal rectal mucosa. The activity of ALDH2-active phenotypes of rectal mucosa was 33% greater than ALDH2-inactive phenotypes at 200 μM acetaldehyde. The protein contents in normal rectal mucosa were in the following order: ADH1 > ALDH2 > ADH3 ≈ ALDH1A1, whereas those of ADH2, ADH4, and ALDH3A1 were fairly low. Both activity and content of ADH1 were significantly decreased in rectal tumors, whereas the ALDH activity remained unchanged. The ADH activity was also significantly reduced in hemorrhoids. ADH4 and ALDH3A1 were uniquely expressed in the squamous epithelium of anus at anorectal junctions. The allele frequencies of ADH1C*1 and ALDH2*2 were significantly higher in colorectal cancer and that of ALDH2*2 also significantly greater in hemorrhoids. In conclusion, ADH and ALDH isozymes are differentially expressed in mucosal cells of rectum and anus. The results suggest that acetaldehyde, an immediate metabolite of ethanol, may play an etiological role in pathogenesis of large bowel diseases.

Bacterial biofilms associated with food particles in the human large bowel

Bacteria within the gastro-intestinal tract affect host function via production of short-chain fatty acids and synthesis of vitamins. Additionally, the commensal enteric bacteria modulate the immune system and provide protection from potentially pathogenic bacteria. Only recently heterogeneous bacterial biofilms were found to be associated with food particles within the intestinal tract. There are a number of studies investigating the formation and function of pathogenic and single-species biofilms, though few studies have investigated the dynamics of multispecies biofilms, especially with regard to food/microbial/host interactions. The scope of this review is to discuss the current knowledge of bacterial biofilms associated with food particles in the human large bowel, examine the established mathematical models depicting bacterial attachment, and elucidate key areas for further research.

Molecular profiling and identification of methanogenic archaeal species from rabbit caecum

During a comparison of 16S rDNA PCR-denaturant gradient gel electrophoresis (DGGE) profiles of methanogenic archaea from rumen fluid, rabbit caecum and pig feces, a unique band common to all rabbit caecum samples was observed. DGGE profiling also showed that the methanogen community from the New Zealand White adult rabbits is different and less complex than the methanogen communities from the rumen and pig feces. Small subunit ribosomal gene sequences of methanogenic archaea were subsequently retrieved from the constructed rabbit caecum 16S rDNA gene library. Results of the phylogenetic analysis indicated that rabbit caecum is inhabited by members of the genus Methanobrevibacter and is possibly one-species dominated, because all the retrieved sequences exhibited similarity values of 99% or higher. This species may well be a novel species of the genus Methanobrevibacter. It belongs to a distinct phylogenetic group containing Methanobrevibacter woesei, Methanobrevibacter thaueri and Methanobrevibacter gottschalkii strains isolated from animal feces, and Methanobrevibacter smithii from the predominating methanogen population of the human large bowel.

Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas

The human large bowel is colonized by complex and diverse bacterial communities. However, the relationship between commensal bowel bacteria and adenomas (colorectal cancer precursors) is unclear. This study aimed to characterize adherent bacteria in normal colon and evaluate differences in community composition associated with colorectal adenomas. We evaluated adherent bacteria in normal colonic mucosa of 21 adenoma and 23 non-adenoma subjects enrolled in a cross sectional study. Terminal restriction fragment length polymorphism, clone sequencing and fluorescent in-situ hybridization analysis of the 16S rRNA genes were used to characterize adherent bacteria. A total of 335 clones were sequenced and processed for phylogenetic and taxonomic analysis. Differences in bacterial composition between cases and controls were evaluated by UniFrac and analysis of similarity matrix. Overall, Firmicutes (62%), Bacteroidetes (26%) and Proteobacteria (11%) were the most dominant phyla. The bacterial composition differed significantly between cases and controls (UniFrac P<0.001). We observed significantly higher abundance of Proteobacteria (p<0.05) and lower abundance of Bacteroidetes (p<0.05) in cases compared to controls. At the genus level, case subjects showed increased abundance of Dorea spp. (p<0.005), Faecalibacterium spp. (p<0.05), and lower proportions of Bacteroides spp. (p<0.03) and Coprococcus spp. (p< 0.05) than controls. Cases had higher bacterial diversity and richness than controls. These findings reveal that alterations in bacterial community composition associated with adenomas may contribute to the etiology of colorectal cancer. Extension of these findings could lead to strategies to manipulate the microbiota to prevent colorectal adenomas and cancer as well as to identify individuals at high risk.

Predicted Apparent Digestion of Energy-Yielding Nutrients Differs between the Upper and Lower Digestive Tracts in Rats and Humans1–3

The apparent digestibility of energy-yielding nutrients (carbohydrate, protein, and fat) was predicted in the human upper digestive tract and large bowel separately for 4 diverse diets containing either a single dietary fiber source [wheat bran and pectin (PE) diets] or mixed fiber sources [low-fiber (LF) and high-fiber (HF) diets). A human balance study was undertaken to determine fecal energy and nutrient excretion and a rat model was used to predict human ileal energy and nutrient excretion. Total tract energy digestibility ranged from 92 (HF diet) to 96% (PE diet and LF diet), while at the ileal level it ranged from 79 to 86% for the HF diet to the LF diet. The predicted upper-tract digestion of starch, sugars, and fat was high, with ileal digestibilities exceeding 90% for all diets. Nonstarch polysaccharides were poorly digested in the upper tract for all diets except in the PE diet. The daily quantity of protein excreted at the ileal level was between 2 (HF diet) and 5 (PE diet) times higher than that at the fecal level. The large differences between fecal and ileal nutrient loss highlight that fecal digestibility data alone provide incomplete information on nutrient loss. There is a need to be able to routinely determine the uptake of energy in the upper and lower digestive tracts separately.

Probiotics: better health from ‘good’ bacteria?

Probiotics are ‘Live microorganisms which when admin-istered in adequate amounts confer a health benefit onthe host’ (WHO 2002). The growing interest in probi-otics in recent years is reflected in both the quantity ofresearch being conducted in this area and the number ofprobiotic products now on the market. These productsexist in many forms, which commonly include yoghurtsand yoghurt drinks, but also include supplements,usually as tablets or capsules.To understand the role of probiotics, it is important tobe aware that many different types of bacteria inhabitthe human large intestine and play a role in mediatingthe digestive process. These bacteria have traditionallybeen classified into groups such as Eubacteria,Clostridia, Bacteroides, Bifidobacteria and Lactobacilli,although developments in the past few years in molecu-lar typing of gut bacteria have added a new dimensionto our understanding of their numbers and diversity. Interms of probiotic organisms, there are two key groupsof bacteria found in the large intestine that are impor-tant. These are Bifidobacteria (which make up approxi-mately 5% of the large intestinal bacteria) andLactobacilli (which, although present as <1% of thebacteria, are very important in terms of their probioticeffect). The numbers of bacteria present in the humanlarge bowel are vast, at around 10

Resistant starches as a vehicle for delivering health benefits to the human large bowel

Resistant starches as a vehicle for delivering health benefits to the human large bowel