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The European Space Agency’s INTErnational Gamma-Ray Astrophysics Laboratory (ESA/INTEGRAL) was launched aboard a Proton-DM2 rocket on 17 October 2002 at 06:41 CEST, from Baikonur in Kazakhstan. Since then, INTEGRAL has been providing long, uninterrupted observations (up to about 47hr, or 170ksec, per satellite orbit of 2.7 days) with a large field-of-view (FOV, fully coded: 100 deg2), millisecond time resolution, keV energy resolution, polarization measurements, as well as additional wavelength coverage at optical wavelengths. This is realized by two main instruments in the 15keV to 10MeV energy range, the spectrometer SPI (spectral resolution 3keV at 1.8MeV) and the imager IBIS (angular resolution: 12arcmin FWHM), complemented by X ray (JEM-X; 3–35keV) and optical (OMC; Johnson V-band) monitor instruments. All instruments are co-aligned to simultaneously observe the target region. A particle radiation monitor (IREM) measures charged particle fluxes near the spacecraft. The Anti-coincidence subsystems of the main instruments, built to reduce the background, are also very efficient all-sky γ-ray detectors, which provide virtually omni-directional monitoring above ∼75keV. Besides the long, scheduled observations, INTEGRAL can rapidly (within a couple of hours) re-point and conduct Target of Opportunity (ToO) observations on a large variety of sources. INTEGRAL observations and their scientific results have been building an impressive legacy: The discovery of currently more than 600 new high-energy sources; the first-ever direct detection of 56Ni and 56Co radio-active decay lines from a Type Ia supernova; spectroscopy of isotopes from galactic nucleo-synthesis sources; new insights on enigmatic positron annihilation in the Galactic bulge and disk; and pioneering gamma-ray polarization studies. INTEGRAL is also a successful actor in the new multi-messenger astronomy introduced by non-electromagnetic signals from gravitational waves and from neutrinos: INTEGRAL found the

Many of the new high energy sources discovered both by INTEGRAL/IBIS and Swift/BAT have been characterised thanks to extensive, multi-band follow-up campaigns, but there are still objects whose nature remains to be asserted. In this paper we investigate the true nature of three high energy sources, IGR J12134-6015, IGR J16058-7253 and Swift J2037.2+4151, employing multiwavelength data from the NIR to the X-rays. Through Gaia and ESO-VLT measurements and through Swift/XRT X-ray spectral analysis, we re-evaluate the classification for IGR J12134-6015, arguing that the source is a Galactic object and in particular a Cataclysmic Variable. We were able to confirm, thanks to NuSTAR observations, that the hard X-ray emission detected by INTEGRAL/IBIS and Swift/BAT from IGR J16058-7253 is coming from two Seyfert 2 galaxies which are both counterparts for this source. Through optical and X-ray spectral analysis of Swift J2037.2+4151 we find that this source is likely part of the rare and peculiar class of Symbiotic X-ray binaries and displays flux and spectral variability as well as interesting spectral features, such as a blending of several emission lines around the iron line complex., Comment: 11 pages, 8 figures, accepted for publication on MNRAS

ESA's INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) was launched on 17 Oct 2002 at 06:41 CEST. Since then, it has been providing long, uninterrupted observations (up to about 47 hr, or 170 ksec, per satellite orbit of 2.7 days) with a large field-of-view (fully coded: 100 deg^2), msec time resolution, keV energy resolution, polarization measurements, as well as additional coverage in the optical. This is realized by two main instruments in the 15 keV to 10 MeV range, the spectrometer SPI (spectral resolution 3 keV at 1.8 MeV) and the imager IBIS (angular resolution 12 arcmin FWHM), complemented by X-ray (JEM-X; 3-35 keV) and optical (OMC; Johnson V-band) monitors. All instruments are co-aligned to simultaneously observe the target region. A particle radiation monitor (IREM) measures charged particle fluxes near the spacecraft. The Anti-coincidence subsystems of the main instruments are also efficient all-sky gamma-ray detectors, which provide omni-directional monitoring above ~75 keV. INTEGRAL can also rapidly (within a couple of hours) re-point and conduct Target of Opportunity observations. INTEGRAL has build an impressive legacy: e.g. discovery of >600 new high-energy sources; first-ever direct detection of 56Ni and 56Co radio-active decay lines from a Type Ia supernova; new insights on positron annihilation in the Galactic bulge and disk; pioneering gamma-ray polarization studies. INTEGRAL is also a successful in multi-messenger astronomy: INTEGRAL found the first prompt electromagnetic radiation in coincidence with a binary neutron star merger. More than 1750 papers based on INTEGRAL data have been published in refereed journals. Here we give a comprehensive update of the satellite status after more than 18 years of operations in a harsh space environment, and an account of the successful Ground Segment., Comment: 29 pages, 20 figures, accepted for publication in special issue of New Astronomy Reviews

ESA's INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) was launched on 17 Oct 2002 at 06:41 CEST. Since then, it has been providing long, uninterrupted observations (up to about 47 hr, or 170 ksec, per satellite orbit of 2.7 days) with a large field-of-view (fully coded: 100 deg^2), msec time resolution, keV energy resolution, polarization measurements, as well as additional coverage in the optical. This is realized by two main instruments in the 15 keV to 10 MeV range, the spectrometer SPI (spectral resolution 3 keV at 1.8 MeV) and the imager IBIS (angular resolution 12 arcmin FWHM), complemented by X-ray (JEM-X; 3-35 keV) and optical (OMC; Johnson V-band) monitors. All instruments are co-aligned to simultaneously observe the target region. A particle radiation monitor (IREM) measures charged particle fluxes near the spacecraft. The Anti-coincidence subsystems of the main instruments are also efficient all-sky gamma-ray detectors, which provide omni-directional monitoring above ~75 keV. INTEGRAL can also rapidly (within a couple of hours) re-point and conduct Target of Opportunity observations. INTEGRAL has build an impressive legacy: e.g. discovery of >600 new high-energy sources; first-ever direct detection of 56Ni and 56Co radio-active decay lines from a Type Ia supernova; new insights on positron annihilation in the Galactic bulge and disk; pioneering gamma-ray polarization studies. INTEGRAL is also a successful in multi-messenger astronomy: INTEGRAL found the first prompt electromagnetic radiation in coincidence with a binary neutron star merger. More than 1750 papers based on INTEGRAL data have been published in refereed journals. Here we give a comprehensive update of the satellite status after more than 18 years of operations in a harsh space environment, and an account of the successful Ground Segment., Comment: 29 pages, 20 figures, accepted for publication in special issue of New Astronomy Reviews

ESA's INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) was launched on 17 Oct 2002 at 06:41 CEST. Since then, it has been providing long, uninterrupted observations (up to about 47 hr, or 170 ksec, per satellite orbit of 2.7 days) with a large field-of-view (fully coded: 100 deg^2), msec time resolution, keV energy resolution, polarization measurements, as well as additional coverage in the optical. This is realized by two main instruments in the 15 keV to 10 MeV range, the spectrometer SPI (spectral resolution 3 keV at 1.8 MeV) and the imager IBIS (angular resolution 12 arcmin FWHM), complemented by X-ray (JEM-X; 3-35 keV) and optical (OMC; Johnson V-band) monitors. All instruments are co-aligned to simultaneously observe the target region. A particle radiation monitor (IREM) measures charged particle fluxes near the spacecraft. The Anti-coincidence subsystems of the main instruments are also efficient all-sky gamma-ray detectors, which provide omni-directional monitoring above ~75 keV. INTEGRAL can also rapidly (within a couple of hours) re-point and conduct Target of Opportunity observations. INTEGRAL has build an impressive legacy: e.g. discovery of >600 new high-energy sources; first-ever direct detection of 56Ni and 56Co radio-active decay lines from a Type Ia supernova; new insights on positron annihilation in the Galactic bulge and disk; pioneering gamma-ray polarization studies. INTEGRAL is also a successful in multi-messenger astronomy: INTEGRAL found the first prompt electromagnetic radiation in coincidence with a binary neutron star merger. More than 1750 papers based on INTEGRAL data have been published in refereed journals. Here we give a comprehensive update of the satellite status after more than 18 years of operations in a harsh space environment, and an account of the successful Ground Segment., Comment: 29 pages, 20 figures, accepted for publication in special issue of New Astronomy Reviews

Many of the new high energy sources discovered both by INTEGRAL/IBIS and Swift/BAT have been characterised thanks to extensive, multi-band follow-up campaigns, but there are still objects whose nature remains to be asserted. In this paper we investigate the true nature of three high energy sources, IGR J12134-6015, IGR J16058-7253 and Swift J2037.2+4151, employing multiwavelength data from the NIR to the X-rays. Through Gaia and ESO-VLT measurements and through Swift/XRT X-ray spectral analysis, we re-evaluate the classification for IGR J12134-6015, arguing that the source is a Galactic object and in particular a Cataclysmic Variable. We were able to confirm, thanks to NuSTAR observations, that the hard X-ray emission detected by INTEGRAL/IBIS and Swift/BAT from IGR J16058-7253 is coming from two Seyfert 2 galaxies which are both counterparts for this source. Through optical and X-ray spectral analysis of Swift J2037.2+4151 we find that this source is likely part of the rare and peculiar class of Symbiotic X-ray binaries and displays flux and spectral variability as well as interesting spectral features, such as a blending of several emission lines around the iron line complex., Comment: 11 pages, 8 figures, accepted for publication on MNRAS

ESA's INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL) was launched on 17 Oct 2002 at 06:41 CEST. Since then, it has been providing long, uninterrupted observations (up to about 47 hr, or 170 ksec, per satellite orbit of 2.7 days) with a large field-of-view (fully coded: 100 deg^2), msec time resolution, keV energy resolution, polarization measurements, as well as additional coverage in the optical. This is realized by two main instruments in the 15 keV to 10 MeV range, the spectrometer SPI (spectral resolution 3 keV at 1.8 MeV) and the imager IBIS (angular resolution 12 arcmin FWHM), complemented by X-ray (JEM-X; 3-35 keV) and optical (OMC; Johnson V-band) monitors. All instruments are co-aligned to simultaneously observe the target region. A particle radiation monitor (IREM) measures charged particle fluxes near the spacecraft. The Anti-coincidence subsystems of the main instruments are also efficient all-sky gamma-ray detectors, which provide omni-directional monitoring above ~75 keV. INTEGRAL can also rapidly (within a couple of hours) re-point and conduct Target of Opportunity observations. INTEGRAL has build an impressive legacy: e.g. discovery of >600 new high-energy sources; first-ever direct detection of 56Ni and 56Co radio-active decay lines from a Type Ia supernova; new insights on positron annihilation in the Galactic bulge and disk; pioneering gamma-ray polarization studies. INTEGRAL is also a successful in multi-messenger astronomy: INTEGRAL found the first prompt electromagnetic radiation in coincidence with a binary neutron star merger. More than 1750 papers based on INTEGRAL data have been published in refereed journals. Here we give a comprehensive update of the satellite status after more than 18 years of operations in a harsh space environment, and an account of the successful Ground Segment., Comment: 29 pages, 20 figures, accepted for publication in special issue of New Astronomy Reviews

© 2019, The Author(s). Background: The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. Objective: To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. Design: In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC–MS/MS. Results: Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = − 0.34, P < 0.01). Conclusions: Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health. Clinical trial registrations: Australian and New Zealand Clinical T

© 2019, The Author(s). Background: The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. Objective: To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. Design: In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC–MS/MS. Results: Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = − 0.34, P < 0.01). Conclusions: Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health. Clinical trial registrations: Australian and New Zealand Clinical T

© 2019, The Author(s). Background: The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. Objective: To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. Design: In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC–MS/MS. Results: Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = − 0.34, P < 0.01). Conclusions: Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health. Clinical trial registrations: Australian and New Zealand Clinical T

© 2019, The Author(s). Background: The Paleolithic diet is promoted worldwide for improved gut health. However, there is little evidence available to support these claims, with existing literature examining anthropometric and cardiometabolic outcomes. Objective: To determine the association between dietary intake, markers of colonic health, microbiota, and serum trimethylamine-N-oxide (TMAO), a gut-derived metabolite associated with cardiovascular disease. Design: In a cross-sectional design, long-term (n = 44, > 1 year) self-reported followers of a Paleolithic diet (PD) and controls (n = 47) consuming a diet typical of national recommendations were recruited. Diets were assessed via 3-day weighed diet records; 48-h stool for short chain fatty acids using GC/MS, microbial composition via 16S rRNA sequencing of the V4 region using Illumina MiSeq. TMAO was quantified using LC–MS/MS. Results: Participants were grouped according to PD adherence; namely excluding grains and dairy products. Strict Paleolithic (SP) (n = 22) and Pseudo-Paleolithic (PP) (n = 22) groups were formed. General linear modelling with age, gender, energy intake and body fat percentage as covariates assessed differences between groups. Intake of resistant starch was lower in both Paleolithic groups, compared to controls [2.62, 1.26 vs 4.48 g/day (P < 0.05)]; PERMANOVA analysis showed differences in microbiota composition (P < 0.05), with higher abundance of TMA-producer Hungatella in both Paleolithic groups (P < 0.001). TMAO was higher in SP compared to PP and control (P < 0.01), and inversely associated with whole grain intake (r = − 0.34, P < 0.01). Conclusions: Although the PD is promoted for improved gut health, results indicate long-term adherence is associated with different gut microbiota and increased TMAO. A variety of fiber components, including whole grain sources may be required to maintain gut and cardiovascular health. Clinical trial registrations: Australian and New Zealand Clinical T

In adults, fermentation of high amylose maize starch (HAMS), a resistant starch (RS), has a prebiotic effect. Were such a capacity to exist in infants, intake of RS might programme the gut microbiota during a critical developmental period. This study aimed to determine if infant faecal inocula possess the capacity to ferment HAMS or acetylated-HAMS (HAMSA) and characterise associated changes to microbial composition. Faecal samples were collected from 17 healthy infants at two timepoints: Preweaning and within 10 weeks of first solids. Fermentation was assessed using in vitro batch fermentation. Following 24 h incubation, pH, short-chain fatty acid (SCFA) production and microbial composition were compared to parallel control incubations. In preweaning infants, there was a significant decrease at 24 h in pH between control and HAMS incubations and a significant increase in the production of total SCFAs, indicating fermentation. Fermentation of HAMS increased further following commencement of solids. Fermentation of RS with weaning faecal inocula increased Shannon’s diversity index (H) and was associated with increased abundance of Bifidobacterium and Bacteroides. In conclusion, the faecal inocula from infants is capable of RS fermentation, independent of stage of weaning, but introduction of solids increases this fermentation capacity. RS may thus function as a novel infant prebiotic.

In adults, fermentation of high amylose maize starch (HAMS), a resistant starch (RS), has a prebiotic effect. Were such a capacity to exist in infants, intake of RS might programme the gut microbiota during a critical developmental period. This study aimed to determine if infant faecal inocula possess the capacity to ferment HAMS or acetylated-HAMS (HAMSA) and characterise associated changes to microbial composition. Faecal samples were collected from 17 healthy infants at two timepoints: Preweaning and within 10 weeks of first solids. Fermentation was assessed using in vitro batch fermentation. Following 24 h incubation, pH, short-chain fatty acid (SCFA) production and microbial composition were compared to parallel control incubations. In preweaning infants, there was a significant decrease at 24 h in pH between control and HAMS incubations and a significant increase in the production of total SCFAs, indicating fermentation. Fermentation of HAMS increased further following commencement of solids. Fermentation of RS with weaning faecal inocula increased Shannon’s diversity index (H) and was associated with increased abundance of Bifidobacterium and Bacteroides. In conclusion, the faecal inocula from infants is capable of RS fermentation, independent of stage of weaning, but introduction of solids increases this fermentation capacity. RS may thus function as a novel infant prebiotic.

OBJECTIVES: Altering FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) intake has substantial effects on gut microbiota. This study aimed to investigate effects of altering FODMAP intake on markers of colonic health in patients with Crohn’s disease. METHODS: After evaluation of their habitual diet, 9 patients with clinically quiescent Crohn’s disease were randomised to 21 days of provided low or typical (“Australian”) FODMAP diets with ≥21-day washout in between. Five-day fecal samples were collected at the end of each diet and analyzed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily. RESULTS: Eight participants collected feces and were adherent to the diets. FODMAP intake differed across the three dietary periods with lowohabitualoAustralian diet. SCFA, pH and total bacterial abundance remained unaltered, but relative abundance was higher for butyrate-producing Clostridium cluster XIVa (P=0.008) and mucus-associated Akkermansia muciniphila (P=0.016), and lower for Ruminococcus torques (P=0.034) during the Australian compared with low FODMAP diet. Results during habitual diet were similar to the low FODMAP intervention, but significantly different to the Australian diet. The diets had no effects on calprotectin, but symptoms doubled in severity with the Australian diet (n=9; Po0.001). CONCLUSIONS: In clinically quiescent Crohn’s disease, altering dietary FODMAP intake is associated with marked changes in fecal microbiota, most consistent with a prebiotic effect of increasing FODMAPs as shown in an irritable bowel/healthy cohort. This strategy might be favorable for gut health in Crohn’s disease, but at the cost of inducing symptoms.

OBJECTIVES: Altering FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) intake has substantial effects on gut microbiota. This study aimed to investigate effects of altering FODMAP intake on markers of colonic health in patients with Crohn’s disease. METHODS: After evaluation of their habitual diet, 9 patients with clinically quiescent Crohn’s disease were randomised to 21 days of provided low or typical (“Australian”) FODMAP diets with ≥21-day washout in between. Five-day fecal samples were collected at the end of each diet and analyzed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily. RESULTS: Eight participants collected feces and were adherent to the diets. FODMAP intake differed across the three dietary periods with lowohabitualoAustralian diet. SCFA, pH and total bacterial abundance remained unaltered, but relative abundance was higher for butyrate-producing Clostridium cluster XIVa (P=0.008) and mucus-associated Akkermansia muciniphila (P=0.016), and lower for Ruminococcus torques (P=0.034) during the Australian compared with low FODMAP diet. Results during habitual diet were similar to the low FODMAP intervention, but significantly different to the Australian diet. The diets had no effects on calprotectin, but symptoms doubled in severity with the Australian diet (n=9; Po0.001). CONCLUSIONS: In clinically quiescent Crohn’s disease, altering dietary FODMAP intake is associated with marked changes in fecal microbiota, most consistent with a prebiotic effect of increasing FODMAPs as shown in an irritable bowel/healthy cohort. This strategy might be favorable for gut health in Crohn’s disease, but at the cost of inducing symptoms.

OBJECTIVES: Altering FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) intake has substantial effects on gut microbiota. This study aimed to investigate effects of altering FODMAP intake on markers of colonic health in patients with Crohn’s disease. METHODS: After evaluation of their habitual diet, 9 patients with clinically quiescent Crohn’s disease were randomised to 21 days of provided low or typical (“Australian”) FODMAP diets with ≥ 21-day washout in between. Five-day fecal samples were collected at the end of each diet and analyzed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily. RESULTS: Eight participants collected feces and were adherent to the diets. FODMAP intake differed across the three dietary periods with lowohabitualoAustralian diet. SCFA, pH and total bacterial abundance remained unaltered, but relative abundance was higher for butyrate-producing Clostridium cluster XIVa (P = 0.008) and mucus-associated Akkermansia muciniphila (P = 0.016), and lower for Ruminococcus torques (P = 0.034) during the Australian compared with low FODMAP diet. Results during habitual diet were similar to the low FODMAP intervention, but significantly different to the Australian diet. The diets had no effects on calprotectin, but symptoms doubled in severity with the Australian diet (n = 9; Po0.001). CONCLUSIONS: In clinically quiescent Crohn’s disease, altering dietary FODMAP intake is associated with marked changes in fecal microbiota, most consistent with a prebiotic effect of increasing FODMAPs as shown in an irritable bowel/healthy cohort. This strategy might be favorable for gut health in Crohn’s disease, but at the cost of inducing symptoms.

OBJECTIVES: Altering FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) intake has substantial effects on gut microbiota. This study aimed to investigate effects of altering FODMAP intake on markers of colonic health in patients with Crohn’s disease. METHODS: After evaluation of their habitual diet, 9 patients with clinically quiescent Crohn’s disease were randomised to 21 days of provided low or typical (“Australian”) FODMAP diets with ≥ 21-day washout in between. Five-day fecal samples were collected at the end of each diet and analyzed for calprotectin, pH, short-chain fatty acids (SCFA) and bacterial abundance. Gastrointestinal symptoms were recorded daily. RESULTS: Eight participants collected feces and were adherent to the diets. FODMAP intake differed across the three dietary periods with lowohabitualoAustralian diet. SCFA, pH and total bacterial abundance remained unaltered, but relative abundance was higher for butyrate-producing Clostridium cluster XIVa (P = 0.008) and mucus-associated Akkermansia muciniphila (P = 0.016), and lower for Ruminococcus torques (P = 0.034) during the Australian compared with low FODMAP diet. Results during habitual diet were similar to the low FODMAP intervention, but significantly different to the Australian diet. The diets had no effects on calprotectin, but symptoms doubled in severity with the Australian diet (n = 9; Po0.001). CONCLUSIONS: In clinically quiescent Crohn’s disease, altering dietary FODMAP intake is associated with marked changes in fecal microbiota, most consistent with a prebiotic effect of increasing FODMAPs as shown in an irritable bowel/healthy cohort. This strategy might be favorable for gut health in Crohn’s disease, but at the cost of inducing symptoms.

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O6-methyl-2-deoxyguanosine (O6MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O6MeG adducts relative to its baseline by 21 % (P< 0·01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P< 0·001) and HRM+HAMSB (P< 0·05) diets when compared with their respective baseline levels, but was lower following the HRM+HAMSB diet compared with the HRM diet (P< 0·05). Relative to its baseline, the HRM+HAMSB diet increased the excretion of SCFA by over 20 % (P< 0·05) and increased the absolute abundances of the Clostridium coccoides group (P< 0·05), the Clostridiumleptum group (P< 0·05), Lactobacillus spp. (P< 0·01), Parabacteroides distasonis (P< 0·001) and Ruminococcus bromii (P< 0·05), but lowered Ruminococcus torques (P< 0·05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P< 0·01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O6MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.

Resistant starch (RS), fed as high amylose maize starch (HAMS) or butyrylated HAMS (HAMSB), opposes dietary proteininduced colonocyte DNA damage in rats. In this study, rats were fed Western-type diets moderate in fat (19%) and protein (20%) containing digestible starches [low amylose maize starch (LAMS) or low amylose whole wheat (LAW)] or RS [HAMS, HAMSB, or a whole high amylose wheat (HAW) generated by RNA interference] for 11 wk (n = 10/group). A control diet included 7% fat, 13% protein, and LAMS. Colonocyte DNA single-strand breaks (SSB) were significantly higher (by 70%) in rats fed the Western diet containing LAMS relative to controls. Dietary HAW, HAMS, and HAMSB opposed this effect while raising digesta levels of SCFA and lowering ammonia and phenol levels. SSB correlated inversely with total large bowel SCFA, including colonic butyrate concentration (R2 = 0.40; P = 0.009), and positively with colonic ammonia concentration (R2 = 0.40; P = 0.014). Analysis of gut microbiota populations using a phylogenetic microarray revealed profiles that fell into 3 distinct groups: control and LAMS; HAMS and HAMSB; and LAW and HAW. The expression of colonic genes associated with the maintenance of genomic integrity (notably Mdm2, Top1, Msh3, Ung, Rere, Cebpa, Gmnn, and Parg) was altered and varied with RS source. HAW is as effective as HAMS and HAMSB in opposing diet-induced colonic DNA damage in rats, but their effects on the large bowel microbiota and colonocyte gene expression differ, possibly due to the presence of other fiber components in HAW.

Resistant starch (RS), fed as high amylose maize starch (HAMS) or butyrylated HAMS (HAMSB), opposes dietary proteininduced colonocyte DNA damage in rats. In this study, rats were fed Western-type diets moderate in fat (19%) and protein (20%) containing digestible starches [low amylose maize starch (LAMS) or low amylose whole wheat (LAW)] or RS [HAMS, HAMSB, or a whole high amylose wheat (HAW) generated by RNA interference] for 11 wk (n = 10/group). A control diet included 7% fat, 13% protein, and LAMS. Colonocyte DNA single-strand breaks (SSB) were significantly higher (by 70%) in rats fed the Western diet containing LAMS relative to controls. Dietary HAW, HAMS, and HAMSB opposed this effect while raising digesta levels of SCFA and lowering ammonia and phenol levels. SSB correlated inversely with total large bowel SCFA, including colonic butyrate concentration (R2 = 0.40; P = 0.009), and positively with colonic ammonia concentration (R2 = 0.40; P = 0.014). Analysis of gut microbiota populations using a phylogenetic microarray revealed profiles that fell into 3 distinct groups: control and LAMS; HAMS and HAMSB; and LAW and HAW. The expression of colonic genes associated with the maintenance of genomic integrity (notably Mdm2, Top1, Msh3, Ung, Rere, Cebpa, Gmnn, and Parg) was altered and varied with RS source. HAW is as effective as HAMS and HAMSB in opposing diet-induced colonic DNA damage in rats, but their effects on the large bowel microbiota and colonocyte gene expression differ, possibly due to the presence of other fiber components in HAW.

Altered gastrointestinal motility is linked with inflammatory bowel disease and other gut disorders. Poor diets which contain high protein, high fat, and low fibre (Western-type) may contribute significantly to the development of diseases of the gastrointestinal tract. While data on colonic contractility is limited, animal and human studies suggest dietary fibre, including resistant starch (RS) may help protect against the effects of the Western-type diet.

Altered gastrointestinal motility is linked with inflammatory bowel disease and other gut disorders. Poor diets which contain high protein, high fat, and low fibre (Western-type) may contribute significantly to the development of diseases of the gastrointestinal tract. While data on colonic contractility is limited, animal and human studies suggest dietary fibre, including resistant starch (RS) may help protect against the effects of the Western-type diet.

Altered gastrointestinal motility is linked with inflammatory bowel disease and other gut disorders. Poor diets which contain high protein, high fat, and low fibre (Western-type) may contribute significantly to the development of diseases of the gastrointestinal tract. While data on colonic contractility is limited, animal and human studies suggest dietary fibre, including resistant starch (RS) may help protect against the effects of the Western-type diet.

Altered gastrointestinal motility is linked with inflammatory bowel disease and other gut disorders. Poor diets which contain high protein, high fat, and low fibre (Western-type) may contribute significantly to the development of diseases of the gastrointestinal tract. While data on colonic contractility is limited, animal and human studies suggest dietary fibre, including resistant starch (RS) may help protect against the effects of the Western-type diet.

Pigs were fed a freeze-dried probiotic (Bifidobacterium animalis CSCC 1941) plus a high-amylose maize starch (HAMS) and a fructooligosaccharide (FOS) separately or together. Fecal output and total and individual major short-chain fatty acid (SCFA) concentrations and excretion were higher and pH waslower with HAMS than with FOS relative to when they were fed a low-amylosemaize starch (LAMS;control). Fecal bifidobacteria numbers and total excretion were equally higher during feeding of FOS or HAMS and highest with HAMS ? FOS. When probiotic supplementation was stopped, bifidobacterianumbers declined rapidly when they were fed LAMS, more slowly with FOS or HAMS, and weremaintained with HAMS ? FOS. The data confirm that both HAMS and FOS are prebiotics and suggest that they act through different mechanisms and that they are most effective in combination. However only HAMS raises fecal SCFA.

Pigs were fed a freeze-dried probiotic (Bifidobacterium animalis CSCC 1941) plus a high-amylose maize starch (HAMS) and a fructooligosaccharide (FOS) separately or together. Fecal output and total and individual major short-chain fatty acid (SCFA) concentrations and excretion were higher and pH waslower with HAMS than with FOS relative to when they were fed a low-amylosemaize starch (LAMS;control). Fecal bifidobacteria numbers and total excretion were equally higher during feeding of FOS or HAMS and highest with HAMS ? FOS. When probiotic supplementation was stopped, bifidobacterianumbers declined rapidly when they were fed LAMS, more slowly with FOS or HAMS, and weremaintained with HAMS ? FOS. The data confirm that both HAMS and FOS are prebiotics and suggest that they act through different mechanisms and that they are most effective in combination. However only HAMS raises fecal SCFA.

Pigs were fed a freeze-dried probiotic (Bifidobacterium animalis CSCC 1941) plus a high-amylose maize starch (HAMS) and a fructooligosaccharide (FOS) separately or together. Fecal output and total and individual major short-chain fatty acid (SCFA) concentrations and excretion were higher and pH waslower with HAMS than with FOS relative to when they were fed a low-amylosemaize starch (LAMS;control). Fecal bifidobacteria numbers and total excretion were equally higher during feeding of FOS or HAMS and highest with HAMS ? FOS. When probiotic supplementation was stopped, bifidobacterianumbers declined rapidly when they were fed LAMS, more slowly with FOS or HAMS, and weremaintained with HAMS ? FOS. The data confirm that both HAMS and FOS are prebiotics and suggest that they act through different mechanisms and that they are most effective in combination. However only HAMS raises fecal SCFA.

Pigs were fed a freeze-dried probiotic (Bifidobacterium animalis CSCC 1941) plus a high-amylose maize starch (HAMS) and a fructooligosaccharide (FOS) separately or together. Fecal output and total and individual major short-chain fatty acid (SCFA) concentrations and excretion were higher and pH waslower with HAMS than with FOS relative to when they were fed a low-amylosemaize starch (LAMS;control). Fecal bifidobacteria numbers and total excretion were equally higher during feeding of FOS or HAMS and highest with HAMS ? FOS. When probiotic supplementation was stopped, bifidobacterianumbers declined rapidly when they were fed LAMS, more slowly with FOS or HAMS, and weremaintained with HAMS ? FOS. The data confirm that both HAMS and FOS are prebiotics and suggest that they act through different mechanisms and that they are most effective in combination. However only HAMS raises fecal SCFA.

Four groups of young pigs (n 6) were fed a diet containing 50 % maize starch as either a highly digestible waxy starch (control; 0 % amylose) or one of three resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85 % amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85 % amylose), or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake and live weight at the end of the study were similar among the four groups. Ileal starch digestibility was lower in pigs fed the three RS diets but was greater for HAMS (88 %) than for HTHAMS (70 %; P < 0·05). Faecal output and large bowel digesta mass, and concentrations and pools of individual and total SCFA were higher (by about two- to threefold; all P < 0·05) and digesta pH lower (by about 1 unit, all P < 0·001) in pigs fed either HAMS or HTHAMS compared to the controls. These differences in biomarkers were seen along the length of the large bowel. Colon length was 0·5–0·9 m longer (19–35 %) in pigs fed the high-RS diets relative to those fed the highly digestible starch diet (P < 0·05). Faecal and proximal colonic lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P < 0·05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches promoted fermentation throughout the large bowel, the data suggest that the effects of HTHAMS may be more pronounced in the distal region compared to those of HAMS.

Four groups of young pigs (n 6) were fed a diet containing 50 % maize starch as either a highly digestible waxy starch (control; 0 % amylose) or one of three resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85 % amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85 % amylose), or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake and live weight at the end of the study were similar among the four groups. Ileal starch digestibility was lower in pigs fed the three RS diets but was greater for HAMS (88 %) than for HTHAMS (70 %; P < 0·05). Faecal output and large bowel digesta mass, and concentrations and pools of individual and total SCFA were higher (by about two- to threefold; all P < 0·05) and digesta pH lower (by about 1 unit, all P < 0·001) in pigs fed either HAMS or HTHAMS compared to the controls. These differences in biomarkers were seen along the length of the large bowel. Colon length was 0·5–0·9 m longer (19–35 %) in pigs fed the high-RS diets relative to those fed the highly digestible starch diet (P < 0·05). Faecal and proximal colonic lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P < 0·05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches promoted fermentation throughout the large bowel, the data suggest that the effects of HTHAMS may be more pronounced in the distal region compared to those of HAMS.

Four groups of young pigs (n 6) were fed a diet containing 50 % maize starch as either a highly digestible waxy starch (control; 0 % amylose) or one of three resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85 % amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85 % amylose), or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake and live weight at the end of the study were similar among the four groups. Ileal starch digestibility was lower in pigs fed the three RS diets but was greater for HAMS (88 %) than for HTHAMS (70 %; P < 0·05). Faecal output and large bowel digesta mass, and concentrations and pools of individual and total SCFA were higher (by about two- to threefold; all P < 0·05) and digesta pH lower (by about 1 unit, all P < 0·001) in pigs fed either HAMS or HTHAMS compared to the controls. These differences in biomarkers were seen along the length of the large bowel. Colon length was 0·5–0·9 m longer (19–35 %) in pigs fed the high-RS diets relative to those fed the highly digestible starch diet (P < 0·05). Faecal and proximal colonic lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P < 0·05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches promoted fermentation throughout the large bowel, the data suggest that the effects of HTHAMS may be more pronounced in the distal region compared to those of HAMS.

Four groups of young pigs (n 6) were fed a diet containing 50 % maize starch as either a highly digestible waxy starch (control; 0 % amylose) or one of three resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85 % amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85 % amylose), or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake and live weight at the end of the study were similar among the four groups. Ileal starch digestibility was lower in pigs fed the three RS diets but was greater for HAMS (88 %) than for HTHAMS (70 %; P < 0·05). Faecal output and large bowel digesta mass, and concentrations and pools of individual and total SCFA were higher (by about two- to threefold; all P < 0·05) and digesta pH lower (by about 1 unit, all P < 0·001) in pigs fed either HAMS or HTHAMS compared to the controls. These differences in biomarkers were seen along the length of the large bowel. Colon length was 0·5–0·9 m longer (19–35 %) in pigs fed the high-RS diets relative to those fed the highly digestible starch diet (P < 0·05). Faecal and proximal colonic lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P < 0·05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches promoted fermentation throughout the large bowel, the data suggest that the effects of HTHAMS may be more pronounced in the distal region compared to those of HAMS.

Four groups of young pigs (n 6) were fed a diet containing 50 % maize starch as either a highly digestible waxy starch (control; 0 % amylose) or one of three resistant starch (RS) diets, namely a high-amylose maize starch (HAMS; 85 % amylose), this starch subjected to hydrothermal treatment (HTHAMS; 85 % amylose), or a blend of HAMS and HTHAMS included in equal amounts, for 21 d. Food intake and live weight at the end of the study were similar among the four groups. Ileal starch digestibility was lower in pigs fed the three RS diets but was greater for HAMS (88 %) than for HTHAMS (70 %; P < 0·05). Faecal output and large bowel digesta mass, and concentrations and pools of individual and total SCFA were higher (by about two- to threefold; all P < 0·05) and digesta pH lower (by about 1 unit, all P < 0·001) in pigs fed either HAMS or HTHAMS compared to the controls. These differences in biomarkers were seen along the length of the large bowel. Colon length was 0·5–0·9 m longer (19–35 %) in pigs fed the high-RS diets relative to those fed the highly digestible starch diet (P < 0·05). Faecal and proximal colonic lactobacilli and bifidobacteria numbers were higher (by 1 and 3 log units; P < 0·05) in pigs fed the HAMS or HTHAMS diets. Although both high-amylose starches promoted fermentation throughout the large bowel, the data suggest that the effects of HTHAMS may be more pronounced in the distal region compared to those of HAMS.

James, S. L., Christophersen, C, T., Bird, A. R., Conlon, M. A., Rosella, O., Gibson, P. R., & Muir, J. G. (2015).Abnormal fibre usage in UC in remission. Gut, 64(4), 562- 570. doi: 10.1136/gutjnl-2014-307198. Available here

Halmos, E. P., Christophersen, C. T., Bird, A. R., Shepherd, S. J., Gibson, P. R., & Muir, J. G. (2015), Diets that differ in their FODMAP content alter the colonic luminal microenvironment. Gut, 64(1), 93-100. doi: 10.1136/gutjnl-2014-307264. Available here

Leu, R. K., Winter, J. M., Christophersen, C., Young, G. P., Humphreys, K. J., Hu, Y., ... Conlon, M. A. (2015). Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial. The British Journal of Nutrition, 114, 220-230. . Available here

Genoni, A., Lo, J., Lyons-Wall, P., Boyce, M. C., Christophersen, C. T., Bird, A., & Devine, A. (2019). A Paleolithic diet lowers resistant starch intake but does not affect serum trimethylamine-N-oxide concentrations in healthy women. British Journal of Nutrition, 121(3), 322-329. Available here

Gopalsamy, G., Mortimer, E., Greenfield, P., Bird, A. R., Young, G. P., & Christophersen, C. T. (2019). Resistant starch is actively fermented by infant faecal microbiota and increases microbial diversity. Nutrients, 11(6), Article 1345. Available here

Belobrajdic, D. P., Jenkins, C. L., Christophersen, C. T., & Bird, A. R. (2018). Cereal fructan extracts alter intestinal fermentation to reduce adiposity and increase mineral retention compared to oligofructose. European Journal of Nutrition, 1-11. Available here

Lockett, T. J., Bird, A. R., Christophersen, C., Clarke, J. M., Conlon, M. A., & Topping, D. L. (2016). Microbes, Metabolites and Health. In: Beale D., Kouremenos K., Palombo E. (eds) Microbial Metabolomics. Springer, Cham. Available here