Intestinal Conventional Ultrasonography, Contrast-Enhanced Ultrasonography and Magnetic Resonance Enterography in Assessment of Crohn's Disease Activity: A Comparison with Surgical Histopathology Analysis.

BACKGROUND AND AIMS: Contrast-enhanced ultrasonography (CEUS) is a potential interesting method for assessing accurately Crohn's disease (CD) activity. We compared the value of intestinal ultrasonography (US) coupled with contrast agent injection with that of magnetic resonance enterography (MRE) in the assessment of small bowel CD activity using surgical histopathology analysis as reference. METHODS: Seventeen clinically active CD patients (14 women, mean age 33 years) requiring an ileal or ileocolonic resection were prospectively enrolled. All performed a MRE and a US coupled with contrast agent injection (CEUS) less than 8 weeks prior to surgery. Various imaging qualitative and quantitative parameters were recorded and their respective performance to detect disease activity, disease extension and presence of complications was compared to surgical histopathological analysis. RESULTS: The median wall thickness measured by US differed significantly between patients with non-severely active CD (n = 5) and those with severely active CD (n = 12) [7.0 mm, IQR (6.5-9.5) vs 10.0 mm, IQR (8.0-12.0), respectively; p = 0.03]. A non-significant trend was found with MRE with a median wall thickness in severe active CD of 10.0 mm, IQR (8.0-13.7) compared with 8.0 mm, IQR (7.5-10.5) in non-severely active CD (p = 0.07). The area under the ROC curve (AUROC) of the wall thickness assessed by US and MRE to identify patients with or without severely active CD on surgical specimens were 0.85, 95% CI (0.64-1.04), p = 0.03 and 0.80, 95% CI (0.56-1.01), p = 0.07, respectively. Among the parameters derived from the time-intensity curve during CEUS, time to peak and rise time were the two most accurate markers [AUROC = 0.88, 95% CI (0.70-1.04), p = 0.02 and 0.86, 95% CI (0.68-1.04), p = 0.03] to detect patients with severely active CD assessed on surgical specimens. CONCLUSION: The accuracy of intestinal CEUS is close to that of conventional US to detect disease activity. A thickened bowel and shortened time to peak and rise time were the most accurate to identify CD patients with severe histological disease activity.

Fetal death in utero and miscarriage in a patient with Crohn's disease under therapy with ustekinumab: case-report and review of the literature.

BACKGROUND: Ustekinumab is a fully human monoclonal antibody against the p40 subunit of interleukin (IL) 12 and 23 which is involved in the pathogenesis of several inflammatory diseases. Ustekinumab is approved for psoriasis and psoriatic arthritis treatment and has been successfully evaluated in phase II and III trials for patients with Crohn's disease (CD). CASE PRESENTATION: We report here the case of a patient who became pregnant during treatment with ustekinumab for a refractory CD and which ended in miscarriage. CONCLUSION: Ustekinumab is a relatively new pharmacotherapy and in addition to this clinical case, we reviewed the published literature concerning the use of this treatment during pregnancy and its consequences on pregnancy and fetus outcome.

Successive treatment with cyclosporine and infliximab in steroid-refractory ulcerative colitis.

OBJECTIVES: Rescue therapy with either cyclosporine (CYS) or infliximab (IFX) is an effective option in patients with intravenous steroid-refractory attacks of ulcerative colitis (UC). In patients who fail, colectomy is usually recommended, but a second-line rescue therapy with IFX or CYS is an alternative. The aims of this study were to investigate the efficacy and tolerance of IFX and CYS as a second-line rescue therapy in steroid-refractory UC or indeterminate colitis (IC) unsuccessfully treated with CYS or IFX. METHODS: This was a retrospective survey of patients seen during the period 2000-2008 in the GETAID centers. Inclusion criteria included a delay of <1 month between CYS withdrawal (when used first) and IFX, or a delay of <2 months between IFX (when used first) and CYS, and a follow-up of at least 3 months after inclusion. Time-to-colectomy, clinical response, and occurrence of serious adverse events were analyzed. RESULTS: A total of 86 patients (median age 34 years; 49 males; 71 UC and 15 IC) were successively treated with CYS and IFX. The median (± s.e.) follow-up time was 22.6 (7.0) months. During the study period, 49 patients failed to respond to the second-line rescue therapy and underwent a colectomy. The probability of colectomy-free survival (± s.e.) was 61.3 ± 5.3% at 3 months and 41.3 ± 5.6 % at 12 months. A case of fatal pulmonary embolism occurred at 1 day after surgery in a 45-year-old man. Also, nine infectious complications were observed during the second-line rescue therapy. CONCLUSIONS: In patients with intravenous steroid-refractory UC and who fail to respond to CYS or IFX, a second-line rescue therapy may be effective in carefully selected patients, avoiding colectomy within 2 months in two-thirds of them. The risk/benefit ratio should still be considered individually.

Colon cancer in inflammatory bowel disease: recent trends, questions and answers.

Patients with chronic colitis (ulcerative colitis or colonic Crohn's disease) have an increased risk of colorectal cancer (CRC). Although most of the molecular alterations reported in sporadic CRC have also been observed in colitis-associated CRC, they do not occur at the same timing and frequency, indicating a different pathophysiology. In particular, recent work highlighted the importance of chronic mucosal inflammation as a key factor favouring colorectal carcinogenesis in these patients. This may also be one of the reasons explaining the role of 5-aminosalicylates as chemopreventive agents for CRC in inflammatory bowel disease (IBD) patients with colonic involvement. Beside chemoprevention, colonoscopic screening and surveillance have been shown to be the cornerstone for CRC prevention and early detection in this particular patients' population. Periodic surveillance colonoscopy to detect dysplasia has been shown to decrease the mortality attributed to CRC. More recently, progress in imaging techniques increased our ability to identify dysplasia, and should probably now be considered to be an integral part of surveillance colonoscopy. In the future, further improvement of our knowledge of CRC biology, refinement of imaging techniques, as well as molecular discovery (e.g. identification of specific mutations in stool DNA extracts), might lead to develop more accurate diagnostic strategies to reduce the morbidity and mortality related to CRC in patients with ulcerative colitis or colonic Crohn's disease.

Long-term efficacy and safety of ustekinumab in 122 refractory Crohn's disease patients: a multicentre experience.

BACKGROUND: Long-term outcome of ustekinumab in Crohn's disease (CD) has not been evaluated. AIM: To evaluate the long-term efficacy and safety of ustekinumab and identify the predictive factors of ustekinumab failure-free persistence in a cohort of anti-TNF refractory CD patients. METHODS: We performed a retrospective multicentre cohort study including all consecutive CD patients who began subcutaneous ustekinumab and presented a clinical response (defined as a significant improvement of CD-related clinical symptoms assessed by the patient's physician leading to continued ustekinumab) during the first year of treatment. Primary outcome was treatment failure defined as withdrawal of treatment due to loss of response, intolerance or need for surgery. RESULTS: Eighty-eight of the 122 (72%) CD patients beginning ustekinumab from March 2011 to December 2014, responded to ustekinumab and were followed up until November 2016. Median time on ustekinumab was 26.6 (13.4-34.4) months. Forty-seven patients (54%) continued ustekinumab with a clinical response and 38 (43%) stopped treatment (32 for failure, five for remission and one for pregnancy). Endoscopic response was observed in 82% of patients with endoscopic evaluation and mucosal healing in 39%. Ustekinumab failure-free persistence rates were 78% at 12 months, 66% at 24 months and 55% at 36 months. No predictive factor of ustekinumab failure-free persistence was identified. One severe adverse event was observed (anal adenocarcinoma). CONCLUSION: In this cohort of refractory CD patients receiving long-term ustekinumab therapy, more than 50% of patients continued ustekinumab treatment with no loss of response, intolerance or surgery and with a good safety profile.

Influence of chronic lactulose ingestion on the colonic metabolism of lactulose in man (an in vivo study).

The effects of a chronic load of nonabsorbable sugars on intracolonic bacterial metabolism of carbohydrates and on H2 breath excretion are disputed. However, most of the discussion relies on indirect evidence or on results of in vitro studies. Thus, we attempted to assess directly and in vivo the effects on intracolonic metabolism of lactulose of a chronic oral load of this nonabsorbable disaccharide. 20 g of lactulose was given orally twice daily during 8 d to eight normal volunteers. In all, breath H2 concentration was measured on days 1 and 8 after ingestion of the morning lactulose dose. In four subjects, stools were collected during 2 d at the beginning and at the end of the lactulose maintenance period to measure fecal pH and daily outputs of carbohydrates and beta-galactosidase. The four other subjects were intubated on days 1 and 8 to measure the pH and the concentrations of carbohydrates, lactic acid, and volatile fatty acids (VFA) in the distal ileum and cecal contents. Moreover, 14C-lactulose was added to cold lactulose and 14CO2 breath outputs determined. Pulmonary H2 excretion fell from day 1 to day 8 (P less than 0.05), whereas 14CO2 excretion increased (P less than 0.01). Fecal water pH, lactic acid, and VFA concentrations did not vary between the two stool collection periods. 24-h fecal weight, fecal water, and carbohydrate outputs showed a trend to decrease between days 1 and 2 and days 7-8, whereas beta-galactosidase activity rose markedly (P less than 0.01). No significant variations were observed for all parameters measured in ileal fluid. In the cecum, areas under the concentration curves decreased from day 1 to day 8 for lactulose, galactose, and fructose (P less than 0.01), while an increase was found for lactic acid (P less than 0.001), acetic acid (P less than 0.0001), and total VFA (P less than 0.001). Cecal fluid pH dropped faster (P less than 0.05) and to a lower level (P less than 0.05) on day 8 than on day 1. These data clearly show that a chronic load of a nonabsorbable sugar induces changes in colonic bacterial metabolic pathways resulting in a better efficiency of the flora to digest the carbohydrate.

Probiotics and irritable bowel syndrome: a rationale for their use and an assessment of the evidence to date.

Probiotics, defined as live organisms that, when ingested in adequate amounts, exert a health benefit on the host, have been used for almost a century in the management of a variety of medical disorders, usually on the basis of little evidence. Advances in our understanding of the gut flora and of its relationship to the host, together with progress in microbiology, molecular biology and clinical research have identified important biological properties for probiotics and demonstrated efficacy in a number of gastrointestinal disorders. The clear delineation of a post-infective variety of irritable bowel syndrome (IBS), as well as the description, in a number of studies, of evidence of low-grade inflammation and immune activation in IBS, suggest a role for a dysfunctional relationship between the indigenous flora and the host in IBS and, accordingly, provide a clear rationale for the use of probiotics in this disorder. Other modes of action, including bacterial displacement and alterations in luminal contents, are also plausible. While clinical evidence of efficacy is now beginning to emerge, a review of available trials emphasises the importance of clear definition of strain selection, dose and viability. This is evidently an area of great potential in IBS and deserves further study at all levels.

Faecal bacterial mass and energetic losses in healthy humans and patients with a short bowel syndrome.

OBJECTIVE: In addition to non-digested nutrients, human stools contain endogenous substrates, among which bacteria are a major component, whose growth may be stimulated when more dietary nutrients are available for bacterial fermentation, as in patients with malabsorption syndrome. We assessed the energy content and composition of both stools and faecal bacteria in healthy volunteers and patients with a short bowel and colon in continuity (SBC). Our goal was to clarify the magnitude of error introduced by the faecal bacteria in the measurement of the digestibility of ingested energy and nutrients. SUBJECTS AND METHODS: We studied six healthy volunteers and six patients with a SBC under free oral intake. The bacterial mass of stools was isolated. In the bacterial fractions and fresh stools, calorie, fat, nitrogen and short-chain fatty acid contents were determined. The Wilcoxon signed rank or the Mann-Whitney tests were used for comparison. RESULTS: In healthy volunteers and patients with SBC, faecal bacterial mass accounted for 44 and 35% of faecal dry weight, and contained 50 and 34% of total faecal energy. In healthy volunteers, the apparent digestibilities when corrected by bacterial constituents (88-97% according to nutrients) were significantly higher than the apparent non-corrected digestibilities (84-94%). In patients with SBC, the corrected apparent digestibilities (69-89% according to nutrients) were significantly higher than the apparent non-corrected digestibilities (54-83%). CONCLUSION: The error introduced by the faecal bacterial fraction when assessing the extent of nutrient digestibility is small in healthy volunteers; it is more pronounced in patients with SBC, reaching 18% for the digestibility of ingested fat.

Azathioprine dose reduction in inflammatory bowel disease patients on combination therapy: an open-label, prospective and randomised clinical trial.

BACKGROUND: Infliximab (IFX) combined with azathioprine (AZA) is more effective than IFX monotherapy in inflammatory bowel disease (IBD). AIM: To identify the AZA optimal dose that is required for efficacy when receiving combination therapy. METHODS: Patients with IBD in durable remission on combination therapy were enrolled in a 1-year, open-label, prospective trial after randomisation into three groups: AZA steady (2-2.5 mg/kg/day, n=28) vs AZA down (dose was halved 1-1.25 mg/kg/day, n=27) vs AZA stopped (n=26). Primary endpoint was failure defined as occurrence of a clinical relapse and/or any change in IBD therapy. RESULTS: Eighty-one patients were included. Five (17.9%), 3 (11.1%), and 8 (30.8%) patients experienced failure at 1 year in groups AZA steady, AZA down and AZA stopped, respectively (P=.1 across the groups). The median trough levels of IFX at inclusion were close to those measured at the end of follow-up in group AZA steady (3.65 vs 3.45 µg/mL, P=.9) and in group AZA down (3.95 vs 3.60 µg/mL, P=.5), whereas these levels dropped from 4.25 to 2.15 µg/mL (P=.02) in group AZA stopped. Four (14.3%), four (14.8%) and 11 (42.3%) patients experienced an unfavourable evolution of IFX pharmacokinetics in groups AZA steady, AZA down and AZA stopped, respectively. A threshold of 6-TGN <105 pmoles/8.108 RBC was associated with an unfavourable evolution of IFX pharmacokinetics. CONCLUSIONS: Under combination therapy, AZA dose reduction, but not withdrawal, appears to be as effective as continuation of AZA at full dose.

Efficacy and safety of golimumab in Crohn's disease: a French national retrospective study.

BACKGROUND: Anti-tumour necrosis factor (TNF) agents have improved the care of Crohn's disease (CD). After the first anti-TNF discontinuation, it is possible to switch to another anti-TNF. Three anti-TNF agents are available for ulcerative colitis (infliximab, adalimumab and golimumab), but only the first 2 have been approved for CD because golimumab has not been studied for this indication. AIM: To report the efficacy and safety of golimumab in CD. METHODS: Crohn's disease patients who received golimumab were identified in 12 French tertiary centres and were retrospectively analysed. The primary endpoint was the duration of golimumab treatment before escalation or discontinuation. The clinical response was defined as a decrease of more than 3 points in the Harvey-Bradshaw index or by global physician assessment. RESULTS: One hundred and fifteen patients were included. The golimumab treatment duration was 9.8 months (0.55-44), and 48.7% of the patients were still under treatment at the end of follow-up. Clinical response was observed in 55.8% of the patients after a mean duration of 3.8 months. The probability of remaining under treatment without escalation at 6, 12 and 24 months was 54.6%, 34.9% and 19.3% respectively. In multivariate analysis, discontinuation of the first anti-TNF agent due to intolerance (odds ratio, OR = 2.16; 95% CI, confidence interval [1.25-3.86]; P = .005) and co-immunosuppression for more than 6 months (OR = 3.98; 95% CI [2.3-7.1]; P < .0001) were predictive factors of efficacy. Six per cent of the patients discontinued treatment due to intolerance. CONCLUSION: After failure of infliximab or adalimumab for Crohn's disease, golimumab was safe and seemed beneficial in half of the patients.

Low-dose lactulose produces a tonic contraction in the human colon.

Lactulose (10-20 g day(-1)) is used to treat constipation. At this therapeutic dose, its effects on colonic motility remain unknown. Twenty-two healthy subjects swallowed a probe with an infusion catheter, six perfused catheters and a balloon connected to a barostat. Colonic phasic and tonic motor activity was recorded in fasting state. In group 1, four volunteers ingested 15 g lactulose and motility was recorded for 5 h after entry of lactulose into the caecum; in group 2, motility was recorded during (3 h) and 2 h after intracolonic infusion of isoosmotic and isovolumetric solutions containing sodium chloride alone (n = 9) or with 15 g lactulose (n = 9). In a last group of volunteers, isotopic colonic transit after ingestion of lactulose (10 g,n = 9) was assessed and compared with a control group (n = 17). Ingestion or intracolonic infusion of 15 g lactulose significantly decreased barostat bag volume (maximal decrease: 45 +/- 12% and 35 +/- 9% of basal value respectively). Phasic contractions remained unchanged. Tonic and phasic motility was unchanged by the isotonic and isovolumetric infusion of saline. Ingestion of lactulose significantly accelerated isotopic colonic transit time compared with the control group. We conclude that in healthy humans, 10-15 g ingestion or intracaecal infusion of lactulose produces a prolonged tonic contraction that may be involved in the laxative effect of lactulose.

Association of Anti-glycan Antibodies and Inflammatory Bowel Disease Course.

BACKGROUND AND AIMS: The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA] antibodies for diagnosis of inflammatory bowel disease [IBD], differentiation between Crohn's disease [CD] and ulcerative colitis [UC], disease stratification including IBD phenotype, and also for determination of the course of the disease, remain unclear. METHODS: A large panel of serological anti-glycan carbohydrate antibodies, including anti-mannobioside IgG antibodies [AMCA], anti-chitobioside IgA [ACCA], anti-laminaribioside IgG antibodies [ALCA], anti-laminarin [anti-L] and anti-chitine [anti-C] were measured in the serum from a cohort of 195 patients with IBD] [107 CD and 88 UC]. The respective accuracy of isolated or combined markers for diagnosis, disease differentiation, stratification disease phenotype, and severity of the disease course, defined by a wide panel of criteria obtained from the past medical history, was assessed. RESULTS: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls [p < 0.0001 and p < 0.0007, respectively]. Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD in comparison with UC (area under receiver operating characteristic curve [AUROC] = 0.70 for each], the adjunction of anti-laminarin antibody substantially improved the differentiation between CD and UC [AUROC = 0.77]. Titres of ACCA [> 51U/ml] and anti-laminarin [> 31U/ml] were significantly linked with a higher association with steroid dependency (odds ratio [OR] =2.0 [1.0-4.0], p = 0.03 and OR = 2.4 [1.1-5.2], p = 0.02, respectively]. We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77U/ml [OR = 4.3; p = 0.002], ASCA > 63U/ml [OR = 3.5; p < 0.009] and at a lesser degree ACCA > 50U/ml [OR = 2.8; p < 0.02] and severe UC course was significantly associated with AMCA > 52U/ml [OR = 3.4; p = 0.04] and ACCA > 25U/ml [OR = 3.0; p < 0.04]. CONCLUSIONS: Anti-glycan antibodies are valuable serological markers, especially AMCA antibodies that may help clinicians to promptly classify patients into high risk for severe disease.

Effect of chronic ingestion of a fermented dairy product containing Lactobacillus acidophilus and Bifidobacterium bifidum on metabolic activities of the colonic flora in humans.

Nine healthy volunteers were studied before, during, and after ingesting a fermented dairy product containing Lactobacillus acidophilus, Bifidobacterium bifidum, and mesophilic cultures (Streptococcus lactis and S cremoris) for 3 wk. Hydrogen and methane productions and fecal beta-galactosidase and beta-glucosidase activities were measured as indicators of fermentation capacity of the colonic flora. Fecal concentrations of nitroreductase, azoreductase, and beta-glucuronidase, which may be implicated in colonic carcinogenesis, were also assessed. Hydrogen and methane productions, fecal beta-galactosidase, beta-glucuronidase, and azoreductase activities did not change over three 3-wk periods whereas fecal beta-glucosidase activity increased (42 +/- 6, 91 +/- 12, and 40 +/- 6 IU/g N, P less than 0.01) and nitroreductase decreased (0.87 +/- 0.13, 0.54 +/- 0.11, and 0.57 +/- 0.08 IU/g N, P less than 0.05).

Starch absorption by healthy man evaluated by lactulose hydrogen breath test.

The amounts of hydrogen produced from starch and lactulose were compared to assess the accuracy of the hydrogen breath test with lactulose as standard to quantify starch malabsorption. The mean amounts of hydrogen produced from starch and lactulose were not different in fecal homogenates and in breath excretion after carbohydrate infusions into the cecum. Known amounts of starch infused into the cecum of 18 subjects were compared with amounts calculated from the total excess excretion of hydrogen in breath computed in relation to hydrogen production after the ingestion of 10 g lactulose; calculated amounts were 3.6 +/- 1.0, 9.9 +/- 1.3, and 22.0 +/- 3.4 g for the infusion of 5, 10, and 25 g of starch, respectively. The lactulose hydrogen breath test based on total excess hydrogen volume provides a valid measurement of the mean amount of starch metabolized in the colon in a group of subjects. However, large individual variations preclude its use in a given subject.

Can diarrhea induced by lactulose be reduced by prolonged ingestion of lactulose?

Twelve healthy volunteers were studied for two test periods, at the beginning of which they ingested a diarrheogenic load (60 g) of lactulose in 350 mL water with 10 g polyethylene glycol 4000 (PEG); the two periods were separated by a lactulose feeding period of 8 d, during which a nondiarrheogenic load (20 g) of lactulose was taken twice daily. The transit time and flow rates of water and lactulose in the distal ileum of four subjects were not different before and after the lactulose feeding period. In the other eight subjects, stool weight and frequency, fecal pH, and fecal outputs of carbohydrates and osmotic moieties after the ingestion of 60 g lactulose dropped significantly (P < 0.05) after the lactulose feeding period, whereas the orofecal transit time and fecal concentrations of beta-galactosidase and lactic acid increased (P < 0.05). We conclude that changes in colonic function induced by prolonged exposure to a nondiarrheogenic amount of lactulose mitigate the severity of the diarrhea because of the larger dose of lactulose.

Effects of milk viscosity on gastric emptying and lactose intolerance in lactose maldigesters.

The possibility of delaying gastric emptying and improving lactose digestion and tolerance by increasing milk viscosity was studied in 13 lactose maldigesters who ingested three test milks with different viscosities (range: 33-1892 mPa.s) in random order at intervals of 1 wk. Each test portion was 500 mL and provided approximately equal to 1900 kJ and 18 g lactose. The different viscosities were obtained by adding varying proportions of rice starch and maltodextrin to a basic milk formula. A combined [13C]glycine-hydrogen breath test was used to measure gastric emptying and lactose digestion simultaneously. Participants reported their gastrointestinal symptoms by using a four-grade scale. Mean (+/- SEM) gastric-emptying half times were 78 +/- 5.7 min for low-viscosity milk (30 mPa.s), 86 +/- 5.0 min for moderate-viscosity milk (80 mPa.s), and 78 +/- 4.5 min for high-viscosity milk (1.9.10(3) mPa.s). Mean orocecal transit times (180 +/- 24, 163 +/- 23, and 180 +/- 24 min, respectively) were not significantly different. There were no milk-dependent differences in breath-hydrogen excretion or in the severity of gastrointestinal symptoms. The milks were well tolerated; > 50% of the subjects reported nondisturbing symptoms or none. We conclude that gastric emptying, orocecal transit time, and lactose digestion and tolerance were not affected by altering milk viscosity. This may have been due to the high energy content of the test milks, which in itself led to slow gastric emptying.

Gastrointestinal effects and energy value of polydextrose in healthy nonobese men.

We studied seven healthy volunteers before and during acute (PD1) and chronic (PD2) ingestion of 30 g polydextrose (PD)/d. The energy value of PD was assessed after [U-14C]PD was added to the 10-g morning dose of PD during PD1 and at the end of PD2. Thirty-one +/- five percent (mean +/- SD) (PD1) and 29 +/- 4% (PD2) of the dose appeared in breath within 48 h. A small fraction of the ingested radioactivity was recovered in urine (4 +/- 1%) and excreted in flatus (< or = 1%) and in feces as volatile fatty acids (VFAs) (< 1%) and bacteria (3-4%); the remaining radioactivity in stools, 33 +/- 3% (PD1) and 32 +/- 4% (PD2), was assumed to be intact PD. Breath excretion of the label was 49 +/- 5% after intracolonic infusion of [U-14C] acetate. The energy value of PD, calculated by means of Miller and Wolin's stoichiometric equation of colonic fermentation, was similar during PD1 and PD2: 4.0 and 6.1 kJ/g, respectively, when breath 14CO2 and VFA production from PD were used for calculation.

Effect of colonic fermentation on respiratory gas exchanges measured in the postabsorptive state.

To assess the effect of colonic fermentation on respiratory gas exchanges, six methane-nonproducing healthy volunteers ingested in the postabsorptive state 1 wk apart either 90 mL lactulose syrup containing 60 g lactulose, 4 g lactose, and 7 g galactose or the same solution but without lactulose (control solution). Six patients with short bowel and remnant colon (SBS) also ingested 90 mL lactulose syrup. Carbon dioxide production (VCO2), oxygen consumption (VO2), respiratory quotient (RQ), and hydrogen excreted in breath were measured basally and for 4 h after the ingestion of solutions. In healthy volunteers within 4 h after ingestion of the control solution, VCO2 and the RQ decreased whereas VO2 remained unchanged. In contrast, in healthy volunteers and patients with SBS, VCO2 and the RQ increased after lactulose ingestion, whereas VO2 did not change. The increase in VCO2 appeared to be accounted for mainly by bacterial production of carbon dioxide and was significantly related to breath-hydrogen concentration (r = 0.56, P < 0.02 for healthy subjects; r = 0.59, P < 0.01 for SBS subjects). A breath-hydrogen test should be performed in conjunction with indirect calorimetry to determine whether colonic fermentation is taking place and, if so, to correct appropriately the VCO2 value in calorimetric equations.