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Statins are usually well-tolerated drugs with a clear dose-dependent efficacy. However, manifestation of statin's side effects also bears a direct relation to higher doses necessary to achieve high impact cholesterol-lowering effects. Nevertheless, the reliance on statin efficacy alone has often left dietary intervention underutilized even though studies have shown a reduction in serum cholesterol levels when dietary fiber intake is increased. In this meta-analysis, we investigated whether the concomitant use of psyllium, a gel-forming viscous soluble fiber, would cause further overall cholesterol lowering in subjects already receiving statins. A systematic review of the medical literature was performed and identified three randomized, controlled clinical studies that evaluated the cholesterol lowering efficacy of statins when given concomitantly with psyllium as a fiber supplement. The duration of the studies ranged from 4 weeks to 12 weeks. The objective of the meta-analysis was to estimate the overall effect of psyllium plus statin versus statin alone. The results of the meta-analysis showed a clinically and statistically significant (p = 0.001) cholesterol lowering advantage for psyllium plus statin combination treatment over a statin alone. Adding psyllium fiber resulted in reductions in low-density lipoprotein-cholesterol equivalent to doubling the statin dose. In conclusion, the data support that psyllium fiber takenbefore meals adds to the efficacy of statins, providing an easy to implement dietary intervention for those who cannot tolerate side effects associated with higher-dose statins., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: Bifidobacterium infantis 35624 is a probiotic that is used often in patients with irritable bowel syndrome (IBS). Non-patients with bowel symptoms may differ from patients with IBS in the impact of their bowel symptoms on illness severity, healthcare and treatment seeking behavior. The aim of this study is to assess the efficacy of B. infantis 35624 (10 9 c.f.u. per day) for the relief of abdominal discomfort and bloating in a non-patient population., Methods: A double-blind, randomized, placebo-controlled, parallel study with a 2-week placebo run-in phase followed by a 4-week intervention phase was conducted at ten clinical centers (USA). Subjects were recruited from the general population by advertisement. The study randomized 302 subjects who experienced abdominal discomfort and bloating ≥2-times per week for at least three months but have not seen a physician or received prescribed medication for their symptoms in the past 12 months. Subjects were assessed for pre- to post-intervention changes in symptom severity (on a 6-point Likert scale; 0=none, 5=very severe) and frequency (symptoms-free days)., Results: A total of 275 subjects (mean age 42 years, 79% female, 74% Caucasian) provided evaluable data. Overall mean severity scores at baseline were 2.4 for abdominal discomfort and 2.5 for bloating with no significant differences between the placebo and probiotic groups. Both groups showed significant (P<0.05) improvement in abdominal discomfort and bloating scores over the 4-week intervention period. Mean severity symptom scores at the end of intervention showed no significant differences between the probiotic and the placebo groups in either abdominal discomfort or bloating (P>0.3). The frequency of abdominal bloating-free days was greater in the B. infantis 35624 group compared to the placebo group (P<0.05). Both regimens were well tolerated., Conclusions: Unlike previous clinical studies in patients with IBS, B. infantis 35624 did not show a significant improvement in the mean severity of symptoms of abdominal discomfort and bloating in a non-patient population. This may be explained by the high placebo effect and the lower impact of functional bowel symptoms in the non-patient population.

The 5-HT(4) receptor agonist tegaserod (TEG) has been reported to modulate visceral pain. However, the underlying mechanism remains unknown. The objective of the present study was to examine the analgesic mechanism and site of action of TEG. In male rats, visceral pain was assessed by measuring visceromotor response (VMR) to colorectal distension (CRD). Inflammation was induced by intracolonic injection of tri-nitrobenzene sulfonic acid (TNBS). The effect of TEG on the VMR was tested by injecting intraperitoneal (i.p.), intrathecal (i.t.), intracerebroventricular (i.c.v) or in the rostroventral medulla (RVM). The effect of the drug was also tested on responses of CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons. Systemic injection of TEG attenuated VMR in naive and TNBS-treated rats. Similarly, supraspinal, but not spinal, injection of TEG attenuated the VMR. While GR113808, (selective 5-HT(4) antagonist) blocked the effect, naloxone (NLX) an opioid receptor antagonist reversed the effect of TEG. Although i.t. NLX did not block the inhibitory effect of TEG in VMR study, i.t. injection of α2-adrenergic receptor antagonist yohimbine blocked the effect of TEG when given systemically. While TEG had no effect on the responses of CRD-sensitive PNA, it inhibited the responses of CRD-sensitive LS neurons in spinal intact condition. This inhibition was blocked by GR113808, NLX and β-funaltrexamine (β-FNA) when injected into the RVM. Results indicate that TEG produces analgesia via activation of supraspinal 5-HT(4) receptors which triggers the release of opioids at supraspinal site, which activates descending noradrenergic pathways to the spinal cord to produce analgesia., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: This review focuses on the health benefits of viscous versus nonviscous soluble fibers, why symptoms can occur with increased fiber consumption, and how to avoid symptoms to improve adherence with a high-fiber diet., Data Sources: Review of scientific literature as well as evidence-based guidelines and resources., Conclusions: While it is generally known that "fiber is good for you," it is less well known that specific health benefits are associated with specific fiber characteristics. Many of the health benefits of fiber can be directly correlated with the viscosity of soluble fibers when hydrated (i.e., gel-forming). A reduction in viscosity of a given fiber will attenuate these health benefits, and a nonviscous fiber does not exhibit these health benefits., Implications for Practice: Increasing the viscosity of chyme with a viscous soluble fiber has been shown clinically to lower cholesterol for cardiovascular health, improve glycemic control in type 2 diabetes, normalize stool form in both constipation (softens hard stool) and diarrhea (firms loose/liquid stool), and improve the objective clinical measures of metabolic syndrome (glycemic control, lipoprotein profile, body mass index/weight loss, and blood pressure)., (©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.)

Background: Irritable bowel syndrome patients have abnormal visceral perception. Probiotic organisms may produce beneficial effects in these patients by reducing visceral hypersensitivity., Aim: To investigate the effects of the probiotic organism, Bifidobacterium infantis 35624, on post-inflammatory visceral hypersensitivity in rats., Methods: Colitis was induced using intracolonic administration of trinitrobenzenesulfonic acid; control rats received saline (day 0). Myeloperoxidase (MPO) levels and colonic damage scores were determined. From days 15-29, rats (n = 10/group) rats were orally dosed with 2 ml of B. infantis ≥ 10(8) colony-forming units/ml or vehicle (MRS broth). A second series of rats (n = 10/group) was dosed in the same manner from days 15-59. The level of colonic stimulation during colorectal distension (CRD) was determined by recording a visceromotor response (VMR) to CRD at 30 mmHg pre- and post-treatment. Post-treatment samples of colonic tissue were weighed, graded for morphologic damage, and assayed for MPO levels., Results: All rats were hypersensitive at day 15. On day 30, hypersensitivity to colorectal distension remained in the vehicle group, but was significantly reduced in the B. infantis group (mean VMR/10 min: vehicle = 15.4 ± 1.0 vs. B. infantis = 7.6 ± 1.0, p < 0.001). A similar, significant effect was observed at day 60. On both day 30 and day 60, tissue weight, colonic damage scores, and MPO levels resembled those of control animals., Conclusions: Oral administration of Bifidobacterium infantis 35624 normalized sensitivity to colorectal distension in a rat model of post-inflammatory colonic hypersensitivity.

Objective: The aim of this study was to compare the effects of two nondigested, nonabsorbed dietary components on objective and subjective measures of gastrointestinal (GI) function., Methods: A placebo-controlled parallel study compared the effects of wheat bran (20 g/day or 40 g/day in cereal), a well-known dietary fiber, with those of olestra (20 g or 40 g/day in potato chips), a nonabsorbed fat, on stool output, stool apparent viscosity (log peak force for extrusion [PF]), stool water content, and GI symptoms. Sixty subjects resided on a metabolic ward for 9 days: 3 days baseline and 6 days treatment., Results: Compared with placebo, consumption of 20 g/day wheat bran for 6 days resulted in a rapid (within 38 h) increase in mean (+/-SE) stool output (placebo, 150 +/- 29 g/day; bran, 246 +/- 35 g/day, p < 0.05), a directional increase in mean stool water content (placebo, 81.2 +/- 0.8%; bran, 83.9 +/- 0.8%), stool water output (placebo, 159 +/- 54 g/day; bran, 238 +/- 30 g/day), and bowel movement frequency (BM/day) (placebo, 2.2 +/- 0.4; bran, 2.6 +/- 0.4), and no stool-softening effect (placebo log PF, 2.9 +/- 0.1 g; bran log PF, 2.9 +/- 0.1 g). Wheat bran 40 g/day results were not significantly different from wheat bran 20 g/day. Compared with placebo, consumption of olestra 20 g/day and 40 g/day for 6 days showed no significant difference in mean stool output (151 +/- 18 g/day and 204 +/- 28 g/day, respectively), mean BM frequency (1.8 +/- 0.2 BM/day and 2.1 +/- 0.3 BM/day, respectively), and stool water output (138 +/- 13 g/day and 184 +/- 31 g/day, respectively), a significant (p < 0.05) decrease in stool water content (75.5 +/- 1.7% and 72.6 +/- 2.2%, respectively), and either no effect on stool apparent viscosity (olestra 20 g/day, mean log PF, 3.0 +/- 0.1 g) or a gradual stool-softening effect beginning study day 6 (olestra 40 g/day, log PF, 2.7 +/- 0.1 g). None of the treatment groups showed a significant increase in GI symptoms compared with placebo., Conclusions: Consumption of wheat bran in excess of levels in a typical Western diet significantly increased stool output, but did not soften normal-viscosity stool nor result in an increase in common GI symptoms. The observed plateau effect for wheat bran at 40 g/day suggests a maximal mechanical stimulatory effect. Consumption of olestra in excess of usual snacking conditions did not result in a significant increase in stool output or common GI symptoms. At the highest level tested, olestra resulted in a gradual stool-softening effect after several days of consumption.

The aim of this study was to characterize propagating contractions in the unprepared colon of freely ambulating mini pigs. A telemetric method was used to record colonic motility continuously for six consecutive days in a 40-cm segment of proximal colon. Propagating contractions occurred over a wide range of propagation rates (0.4-16.7 cm/sec), peak amplitudes (10-116 mm Hg) and pressure wave durations (5.3-40.0 sec). Propagating contractions were divided into two groups by duration and wave-form: short-duration symmetrical and long-duration asymmetrical. Short-duration (7.8 +/- 0.9 sec) symmetrical wave-from propagating contractions exhibited a higher frequency (27.9 +/- 2.6 events/day), more rapid propagation rate (3-16.7 cm/sec; mean +/- SEM: 4.9 +/- 1.7 cm/sec), and a lower peak amplitude (31.2 +/- 0.9 mm Hg) compared to long-duration (19.2 +/- 5.1 sec) asymmetrical propagating contractions, which were less frequent (6.1 +/- 0.7 events/day), slower in propagation rate (0.4-2 cm/sec; mean +/- SEM: 1.5 +/- 0.7 cm/sec), and higher in peak amplitude (51.6 +/- 2.4 mm Hg). The results show that propagating contractions occur over a wide spectrum, from short-duration, low-amplitude, rapidly propagating contractions to long-duration, high-amplitude, slowly propagating contractions.

The aim of this study was to determine how bulk fibers and calcium docusate affect regional dehydration and digesta viscosity throughout the large intestine. Fifty-two pigs were fed a chow diet supplemented with a bulk laxative, placebo, or calcium docusate for three days, after which the pigs were sacrificed and the contents of the large bowel were analyzed. Digesta occurred as a continuum from liquid (cecum, 91.2% water content) to solid (rectum, 70.5% water content). The observed 20.7% difference in water content resulted in a 240-fold increase in viscosity. Half of this water is reabsorbed in the first 18% of the large bowel length where viscosity remains relatively low. Compared to placebo, calcium docusate and calcium polycarbophil had no significant effect on digesta water content or viscosity, polycarbophil exhibited significantly (P < 0.05) lower digesta viscosity in three bowel segments, and psyllium exhibited significantly (P < 0.01) lower viscosity in six bowel segments and higher water content in nine bowel segments. In conclusion, the majority of digesta dehydration occurs early in the proximal large bowel, while the greatest increases in viscosity occur in the distal bowel. Relatively small decreases in digesta water content result in large increases in digesta viscosity. Psyllium, and to a lesser extent polycarbophil, are able to resist dehydration, resulting in a softer digesta.

Regulation of colon function depends on the location of nerve cell bodies and the distribution of intrinsic nerve fibers in the myenteric plexus. The morphology and projections of myenteric neurons through colonic fiber bundles in cat colon were determined using in vivo retrograde transport of HRP and Fast blue. Myenteric neurons were found to project from at least 5 to 59 mm orad (mean: 42 mm) or aborad (mean: 54 mm) through colonic fiber bundles. Approximately 73% of labelled cells were in ganglia within 2.8 mm of colonic fiber bundles in the axis of circular muscle fibers; none was beyond 7.7 mm. There were 2 soma morphologies. One type (Dogiel type I) had a mean soma diameter of 40.5 microns and had a rough somal surface. There were few if any short, broad dendrites, but its one long process extended to a branch point of an adjacent colonic fiber bundle. The other type (Dogiel type III) had a mean soma diameter of 26.4 microns, had a smooth somal surface and had few if any fine dendrites. It also projected a single long axon to colonic fiber bundles. There were twice as many Dogiel type III neurons. We conclude that myenteric neurons in the cat colon project both orad and aborad over relatively long distances through colonic fiber bundles where they form another intrinsic neuronal connection for the myenteric plexus.