Fiber Deficiency Research Articles

Nutriceuticals in Cardiovascular Disease

In recent years, there has been a growing interest in the use of dietary fiber in health maintenance and disease prevention. A deficiency of fiber in the Western diet may be contributing to the current epidemics of diabetes mellitus, coronary artery disease (CAD), and colonic cancer. The awareness of fiber as a dietary supplement may have contributed to the reported 30% decline in death rate from CAD observed over the past 15 years. Psyllium is a soluble gel-forming fiber that has been shown to bind to the bile acids in the gut and prevent their normal reabsorption, similar to the bile acid sequestrant drugs. Psyllium is useful as an adjunct to dietary therapy (step 1 or step 2 American Heart Association [AHA] diet) in the treatment of patients with mild-to-moderate hypercholesterolemia. In combination with other cholesterol-lowering drugs, such as statins, psyllium provides an added benefit on cholesterol lowering, and is well tolerated and cost-effective.

Fibre‐free diet leads to impairment of neuronally mediated muscle contractile response in rat distal colon

Dietary fibre consumption is known to be beneficial to increase stool bulk and frequency. In contrast, it is unclear whether chronic dietary fibre deficiency affects colonic motor functions, especially neuronally mediated muscle contractions. In this study, rats were fed a fibre-free diet or diet containing dietary fibre (cellulose or guar gum) for 27 days. Furthermore, neurogenic and myogenic contractions were evaluated in circular and longitudinal muscle strips of the distal colon. Additionally, the number of enterochromaffin (EC) cells, which play important roles in the initiation of the peristaltic reflex, was also examined by immunohistochemistry for serotonin. Myogenic contractions induced by carbachol or substance P were examined in the presence of tetrodotoxin. Circular muscle was hyposensitive to carbachol, but longitudinal muscle was hypersensitive to substance P in the fibre-free group. Nerve-mediated circular (5-20 Hz) and longitudinal (1-2 Hz) muscle contractions evoked by electrical field stimulation were attenuated in the fibre-free group and the latter response was almost abolished by atropine, suggesting functional changes of cholinergic neurons. EC cell number was decreased in the fibre-free group. In conclusion, changes in neurogenic and myogenic contractions and a decrease in EC cell number observed may affect colonic motility of the fibre-free group.

A Hypothesis: Is Diverticulitis a Type of Inflammatory Bowel Disease?

It is accepted by epidemiologists that diverticula formation in the colon is related to a deficiency in dietary fiber intake, but the cause of acute diverticulitis remains unknown. A hypothesis is presented that acknowledges from the literature that fiber deficiency is also related to an altered intestinal microecology with a change in the bacterial flora. It is hypothesized that the change in the flora with a decrease in their influence on the immune process permits a low-grade chronic inflammation in the mucosa, which is the first step in developing an acute infection of diverticula or diverticulitis. There is some evidence that the low-grade chronic inflammation is present in subjects with diverticula, which is the forerunner of acute diverticulitis. This hypothesis is strengthened by early reports that anti-inflammatory mucosal agents such as mesalamine and immune process regulators such as probiotics may improve diverticulitis.

Central core disease is due to RYR1 mutations in more than 90% of patients

Ryanodine receptor 1 (RYR1) gene mutations are associated with central core disease (CCD), multiminicore disease (MmD) and malignant hyperthermia (MH), and have been reported to be responsible for 47-67% of patients with CCD and rare cases with MmD. However, to date, the true frequency and distribution of the mutations along the RYR1 gene have not been determined yet, since mutation screening has been limited to three 'hot spots', with particular attention to the C-terminal region. In this study, 27 unrelated Japanese CCD patients were included. Clinical histories and muscle biopsies were carefully reviewed. We sequenced all the 106 exons encoding RYR1 with their flanking exon-intron boundaries, and identified 20 novel and 3 previously reported heterozygous missense mutations in 25 of the 27 CCD patients (93%), which is a much higher mutation detection rate than that perceived previously. Among them, six were located outside the known 'hot spots'. Sixteen of 27 (59%) CCD patients had mutations in the C-terminal 'hot spot'. Three CCD patients had a probable autosomal recessive disease with two heterozygous mutations. Patients with C-terminal mutations had earlier onset and rather consistent muscle pathology characterized by the presence of distinct cores in almost all type 1 fibres, interstitial fibrosis and type 2 fibre deficiency. In contrast, patients with mutations outside the C-terminal region had milder clinical phenotype and harbour more atypical cores in their muscle fibres. We also sequenced two genes encoding RYR1-associated proteins as candidate causative genes for CCD: the 12 kD FK506-binding protein (FKBP12) and the alpha1 subunit of L-type voltage-dependent calcium channel or dihydropyridine receptor (CACNA1S). However, no mutation was found, suggesting that these genes may not, or only rarely, be responsible for CCD. Our results indicate that CCD may be caused by RYR1 mutations in the majority of patients.

Management of diverticular disease is changing

Diverticular disease of the colon is primarily a disease of humans living in westernized and industrialized countries. Sixty percent of humans living in industrialized countries will develop colonic diverticula. It is rare before the age of 40, but more prone to complications when it occurs in the young. By age 80, over 65% of humans have colonic diverticula. The cause remains uncertain, but epidemiologic studies attribute it to dietary fiber deficiency. The cause of diverticulitis remains uncertain, but new observations and hypotheses suggest that it is due to chronic inflammation in the bowel wall. Standard medical therapies of bowel rest and antibiotics are still the recommended treatment. However, changing concepts and new therapies indicate that anti-inflammatory agents such as mesalamine and possibly probiotics may be helpful in shortening the course and perhaps preventing recurrences. Standard surgical treatment for perforation for severe acute disease has developed so that two-stage procedures are recommended. In addition, laparoscopic surgery has proven safe and may slowly become the technique of choice.

Absence of mutations in the survival motor neuron cDNA from labrador retrievers with an inherited myopathy

The clinical phenotype of hereditary myopathy of labrador retrievers is consistent, but the pathological changes within muscle biopsy specimens can vary from type 1 fibre predominance (type 2 fibre deficiency)...

Preventive therapy in perforated colonic diverticular disease? Calcium channel blockers may hold the key

Preventive therapy in perforated colonic diverticular disease? Calcium channel blockers may hold the key

Long-Term Synaptic Changes Induced in the Cerebellar Cortex by Fear Conditioning

To better understand learning mechanisms, one needs to study synaptic plasticity induced by behavioral training. Recently, it has been demonstrated that the cerebellum is involved in the consolidation of fear memory. Nevertheless, how the cerebellum contributes to emotional behavior is far from known. In cerebellar slices at 10 min and 24 hr following fear conditioning, we found a long-lasting potentiation of the synapse between parallel fibers and Purkinje cells in vermal lobules V-VI, but not in the climbing fiber synapses. The mechanism is postsynaptic, due to an increased AMPA response. In addition, in hotfoot mice with a primary deficiency of the parallel fiber to Purkinje cell synapse, cued (but not contextual) fear conditioning is affected. We propose that this synapse plays an important role in the learned fear and that its long-term potentiation may represent a contribution to the neural substrate of fear memory.

The natural history of diverticulitis: fact and theory.

Epidemiological and anatomic evidence indicates that approximately 60% of humans of westernized societies living into the sixth decade will develop diverticulosis of the colon. The cause remains unknown, but epidemiological studies indicate it is a combination of decreased dietary fiber intake and increased intracolonic pressure. The intraluminal pressure exerted on the wall causes a diverticular outpocketing at any one of the three areas in which vessels enter the wall. In this paper, we advance a hypothesis that fiber deficiency not only leads to diverticula formation but also causes a change in the microecology that results in decreased colon immune response and permits a low-grade chronic inflammatory process that precedes a full-blown acute diverticulitis. Pathophysiologic studies reveal that complications do not occur until there is microperforation through the wall of the diverticulum into the pericolic tissue. The perforation might be small and cause a microabscess, or extend to a phlegmon, or extend to a large abscess formation. Free perforation occurs rarely, but fistulization does occur and most commonly to the bladder. The clinical findings vary. Most often, the clinical picture is one of fever, abdominal pain, a change in bowel habit, and localizing findings associated with leukocytosis. Computerized tomography scanning has become the procedure of choice to evaluate the symptoms since it is of less risk than a barium enema and obtains more information. The differential diagnosis may be difficult but usually can be made with accuracy. Medical treatment is preferred with appropriate antibiotic therapy and variations in fiber intake. When abscess occurs, percutaneous drainage may be tried, but when it is unsuccessful, surgical intervention is necessary. Sudden hemorrhage from a vessel in diverticula may also occur. It is estimated that approximately 20% of all patients that develop diverticula will have either inflammatory or bleeding episodes. In conclusion, fiber deficiency results in diverticular formation and a chronic inflammation that may progress to acute or chronic diverticulitis that can be treated medically but may require surgical intervention.

Diagnosis and management of diverticulitis in women

Diverticular disease is thought to be related to dietary fiber deficiency and has a higher incidence in developed countries and in older patients, especially women. Diverticulitis is an inflammatory process of colonic diverticula that commonly presents with lower abdominal pain, fever, and leukocytosis. The differential diagnosis of diverticulitis includes ruptured ovarian cyst, ovarian torsion, tubo-ovarian abscess, ectopic pregnancy, pelvic inflammatory disease, appendicitis, Crohn's disease, colon cancer, ischemic colitis, pseudomembranous colitis, complicated ulcer disease, and urologic disease. Treatment may be medical or surgical, depending upon the severity of the episode and the presence or absence of complications.

Glycosaminoglycan profiles of myxomatous mitral leaflets and chordae parallel the severity of mechanical alterations

ObjectivesThis biochemical study compared the extracellular matrix of normal mitral valves and myxomatous mitral valves with either unileaflet prolapse (ULP) or bileaflet prolapse (BLP). BackgroundMyxomatous mitral valves are weaker and more extensible than normal valves, and myxomatous chordae are more mechanically compromised than leaflets. Despite histological evidence that glycosaminoglycans (GAGs) accumulate in myxomatous valves, previous biochemical analyses have not adequately examined the different GAG classes. MethodsLeaflets and chordae from myxomatous valves (n = 41 ULP, 31 BLP) and normal valves (n = 27) were dried, dissolved, and assayed for deoxyribonucleic acid, collagen, and total GAGs. Specific GAG classes were analyzed with selective enzyme digestions and fluorophore-assisted carbohydrate electrophoresis. ResultsBiochemical changes were more pronounced in chordae than in leaflets. Myxomatous leaflets and chordae had 3% to 9% more water content and 30% to 150% higher GAG concentrations than normal. Collagen concentration was slightly elevated in the myxomatous valves. Chordae from ULP had 62% more GAGs than those from BLP, primarily from elevated levels of hyaluronan and chondroitin-6-sulfate. ConclusionsThe GAG classes elevated in the myxomatous chordae are associated with matrix microstructure and elastic fiber deficiencies and may influence the hydration-related “floppy” nature of these tissues. These abnormalities may be related to the reported mechanical weakness of myxomatous chordae. The biochemical differences between ULP and BLP confirm previous mechanical and echocardiographic distinctions.

Colonic mucin: methods of measuring mucus thickness.

Mucus is a water-insoluble gel secreted by the gastrointestinal tract. It exists as a protective gel layer adherent to the epithelial surface of the stomach, small intestine and colon. The mucus gel is composed of 1-10 % (w/v) mucin glycoprotein in a plasma-like fluid. Since the mucus gel is predominantly water, standard histological techniques dehydrate the mucus, making visualisation of the functional barrier difficult. Specialist techniques have been developed to enable visualisation of the intact mucus layer. A simple histological method using snap-frozen tissue, sectioned with a cryostat and stained with modified periodic acid-Schiffs/Alcian blue in mucus-preserving conditions will be described. A second powerful in vivo animal model is described which enables measurement of mucus secretion over time. The use of these two methods has allowed the characterisation of the normal mucus layer in the colon and the determination of how it is affected by disease and dietary intervention, in particular the effect of dietary fibre, and evidence that fibre deficiency results in colonic mucosal fragility is presented.

Colonic mucus: secretion and turnover in relation to dietary fibre intake.

The colon is subjected to a myriad of potentially damaging agents that may reside within the lumen for 1-2 d. Its first line of defence against these agents is the protective mucus bilayer that lines the entire colonic mucosa. This bilayer acts as a physical barrier to mucosal aggressors and also reduces shear stress to the mucosa. These actions are dependent on the unstimulated ('resting') colonic mucus thickness, and also on the rate that this layer can be replenished. The colonic mucus layer is altered in a number of colonic diseases that have been linked to a deficiency of fibre in the diet. The action of fibre intake on colonic mucus thickness and secretion is unknown. Using an in vivo rat model it has been demonstrated that: (1). fibre deficiency leads to a decreased protective potential of the mucus layer (e.g. the mean resting mucus thickness of the fibre-deficient group (429 microm) was significantly lower than its respective control (579 microm; P< 0-001), as was its total mucus secretion over 6 h (270 microm v. 541 microm; P<0-01); (2). specific fibre types in the diet alter the secretion dynamics of colonic mucus (e.g. a cellulose-based diet reduces total mucus secretion over 6 h compared with its control (175 microm v. 463 microm). Analysis of the diets suggested a necessity for both soluble and insoluble fibre types in the diet to increase mucosal protection.

Effects of Age and Dietary Fibre Level on Caecal Microbial Communities of Conventional and Specific Pathogen-Free Rabbits

Caecal community structure in conventional and specific pathogen-free (SPF) rabbits was assessed by performing dot-blot hybridization with 16S rRNA targeted oligonucleotide probes. The variation of the caecal flora was analysed according to age (18–70 days old), nutritional status (acid detergent fibre=19% in standard and 9% in fibre-deficient diet) and rabbit health (healthy vs diarrhoeic). Caecal flora was stabilized at around 25–28 days. Bacteria and archaea represented 73% and 22%, respectively, of the total microbial communities at weaning (28 days). Cellulolytic bacteria ( Ruminococcus albus, R. flaefaciens, Fibrobacter succinogenes and F. intestinalis ) represented <7% of total bacteria, with a predominance of R. flaefaciens and R. albus , respectively, for conventional and SPF rabbits. Bacterial and archaeal rRNAs were twofold higher in conventional than in SPF rabbits, fed standard diet (p<0.001). In conventional rabbits, archaeal community was twofold higher with standard diet than with fibre-deficient diet. In both types of rabbits, quantities of Flexibacter-Cytophaga-Bacteroides rRNA were twofold higher with fibre-deficient diet than with standard diet. In diarrhoeic conventional rabbits, the proportion of eukaryal rRNA increased 4-fold, but proportions of bacterial and archaeal rRNA decreased by 1-, 2- and 6-fold, respectively. The quantities of rRNA of F. succinogene s and F. intestinalis in conventional rabbits were, respectively 17 and 5 times higher in sick than in healthy animals, and decreased by 7-fold for R. albus . This study shows some microbial interactions according to nutrition and health of the rabbit. Key words : rabbit, caecal flora, fibre deficiency, oligonucleotide probes, enteropathy, specific pathogen-free, microbial community balance.

Trends in dietary fiber intake in Japan over the last century.

Insufficient intake of dietary fiber (DF) is currently a major problem in the overall promotion of health in the general population in Japan. To analyze the time trends in DF intake, including DF density (total DF intake/1,000 kcal), and the ratio of water-insoluble fiber to water-soluble fiber (IS ratio) in Japan. The time trend in DF intake in Japan was calculated from data compiled in the Japanese National Nutrition Survey. The mean daily DF intake (total DF intake) in 1952 was 20.5 g/day, which rapidly declined to about 70 % of the 1952 level in 1970, after which there was little change to 1998. DF density in 1952 was 9.7 g/1000 kcal, which declined by about 30 % in 1970, and remained at about the same level to 1998. The IS ratio has remained stable over this period. Whereas total DF intake and DF density in Japan are similar to those in Western countries, the IS ratios are higher in Japan. Therefore, the higher incidence of, and mortality from, colon diverticulosis, coronary heart disease, hyperlipidemia, etc., which are all thought to be related to fiber deficiency, in Western countries compared to Japan might be due to the differences in the IS ratio. A decline in total DF intake and DF density is predicted for Japan in the future, because these parameters were lower among the younger generation. This may be due to the marked changes in the dietary habits of the younger generation, and is a problematic trend for Japanese health.

Microbial activity in the caecum of the rabbit around weaning: impact of a dietary fibre deficiency and of intake level

The current study was designed to evaluate the caecal microbial activity in the young rabbit, as influenced by dietary fibre concentration and feed intake level. Caecal fermentative activity and bacterial fibrolytic activity were measured before and after weaning (28-day old) in young (six litters of eight per diet) fed before weaning a fibre deficient diet “DF” (92 g acid detergent fibre (ADF) kg −1), or a standard fibre diet (165 g ADF kg −1) containing either a standard (diet SF) or an excessive methionine level (diet MSF). The effect of the dietary fibre level on microbial activity was evaluated by comparing DF and SF groups. The fibre effect itself, without change in intake level, was estimated by comparing DF and MSF groups, since a high level of methionine reduces the intake level in rabbits. Feed intake (from 28 to 42 days) was 13% lower for MSF than for SF group, but was similar to DF group. Between 21 days of age and weaning, caecal volatile fatty acid (VFA) concentration doubled and then slightly increased until 42 days of age. A linear reduction for propionate and, conversely, an increase in butyrate molar proportions were observed with age. Until weaning, VFA concentrations were similar between the three diets, although it tended to be lower for DF ( P=0.067). Subsequently, VFA concentration of SF group increased, while for DF it decreased (respectively, 72 mM l −1 versus 40 mM l −1 at 42 days, P<0.05). Pectinase, xylanase and cellulase activity of bacteria increased by 80% between 25 and 34 days of age. The bacterial fibrolytic activity was not significantly affected by the reduction of the intake (MSF versus SF), while fermentative parameters of MSF group were intermediate between SF and DF, suggesting that fibre effect partly depended on the intake level.

The significance of type 1 fiber atrophy (hypotrophy) in childhood neuromuscular disorders

To determine the incidence of selective type 1 fiber atrophy (hypotrophy) and its possible significance in various muscle diseases of childhood, we reviewed 2212 muscle biopsies from children which we had examined in the past 20 years histochemically with ATPase staining. Type 1 fiber atrophy was seen in a variety of neuromuscular disorders, but predominantly in congenital myopathies, including all patients with congenital fiber type disproportion myopathy (20 patients), central core disease (12 patients) and multicore disease (four patients). Although type 1 fiber atrophy was not a constant feature in nemaline myopathy and myotubular myopathy, all patients with these diseases had abnormal fiber type distribution which included type 1 fiber predominance both with and without type 2B fiber deficiency. Together with abnormal fiber type distribution, type 1 fiber atrophy was a common finding in childhood neuromuscular disorders, especially congenital myopathies.

Impact of fibre deficiency and sanitary status on non-specific enteropathy of the growing rabbit

The effects of a sharp reduction in dietary fibre level (19 to 9% ADF resp. for S and D diet) were studied on the health status and performances of two groups of rabbits with different sanitary statuses: conventional ( n = 224) and specified pathogen free 'SPF' ( n = 72) from 28 to 70 days of age. Digestive pathology was monitored daily and individually along the whole fattening period (28-70 d old) to precisely quantify the impact of a fibre deficiency on rabbit health. Diarrhoea was the most common symptom of enteritis due to fibre deficiency (90% of cases). The major diges- tive lesions were dilatation of the caeco-colic segment (30%) and a watery intestinal and caecal digesta (60%). The digestive troubles had a similar expression with respect to sanitary status or diet effect. The mortality and the Health Risk index (HRi = mortality + morbidity rate) respectively reached 25 and 60% with the fibre deficient diet D (28-70 d period) compared to 9 and 41% for the standard diet S ( P < 0.05). The digestive disturbances appeared mainly during the period 28-42 d for SPF rabbits, and later for the C rabbits (43-56 d). Morbidity, HRi and the duration of diarrhoea were respectively 7, 2 and 3 times higher for C rabbits as compared to the SPF rabbits. A syner- getic effect of fibre deficiency and conventional sanitary status was observed on the incidence and inten- sity of digestive troubles. For individually caged rabbits, morbidity seemed to be mainly linked to the sanitary status of the animal (SPF or conventional), while the mortality level was enhanced by a fibre deficiency. The fibre supply thus seemed to prevent morbidity from evolving into mortality. In conclusion, non-specific enteropathy depends jointly on sanitary and nutritional status of the animals. rabbit / fibre deficiency / sanitary status / digestive pathology / nutrition

Frequency analysis of surface EMG on knee extensors with anterior cruciate ligament insufficiency

The muscle strength of knees with an injured anterior cruciate ligament (ACL) is generally assessed by the peak of the isokinetic muscle contraction. However, assessment of the characteristics of muscle contraction, such as the contraction velocity and contraction endurance, has been largely ignored due to a lack of data. In this study, we have performed frequency analysis of the surface electromyograms during sustained isometric contraction of the quadriceps femoris muscle in 22 knees with ACL deficiency to evaluate the characteristics of muscle contraction. Concerning the time-related changes in the mean power frequency (MPF), the decrease with time was smaller than normal (reflecting a deficiency in the number of fast-twitch fibers) in the rectus femoris and vastus medialis muscles of the injured limb in many subjects. However, a slightly different pattern was observed in the vastus lateralis muscle, which showed little difference between the injured and intact limbs. Therefore the vastus lateralis muscle was considered to be less affected by an ACL deficiency than the other two muscles. The time-related changes in the MPF in the ACL deficient limb were clearly different from those in the intact limb and a deficiency in the fast-twitch fibers was suggested. Therefore a frequency analysis of the surface electromyograms was considered to allow detection of qualitative changes, such as of muscle fiber deficiency, as well as detection of changes in the simple muscle strength.

Congenital familial myopathy with type 2 fiber hypoplasia and type 1 fiber predominance

A 12-month-old girl with delayed developmental milestones, due to muscle hypotonia and weakness from early infancy, exhibited type 2 fiber hypoplasia. A muscle biopsy specimen disclosed type 1 fiber predominance and type 2B fiber deficiency compatible with congenital myopathy. During the following 4 years, she continued to have mild muscle weakness, but no mental retardation. Her mother had similar symptoms from early infancy with minimal progression. Although type 2 fiber hypoplasia is a non-specific finding in various diseases, it may be a specific finding in a limited number of patients with hereditary congenital non-progressive myopathy.