There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented.

IMPORTANCE High-intensity, aerobically prepared fecal microbiota transplantation (FMT) has demonstrated efficacy in treating active ulcerative colitis (UC). FMT protocols involving anaerobic stool processing methods may enhance microbial viability and allow efficacy with a lower treatment intensity. OBJECTIVE To assess the efficacy of a short duration of FMT therapy to induce remission in UC using anaerobically prepared stool. DESIGN, SETTING, AND PARTICIPANTS A total of 73 adults with mild to moderately active UC were enrolled in a multicenter, randomized, double-blind clinical trial in 3 Australian tertiary referral centers between June 2013 and June 2016, with 12-month follow-up until June 2017. INTERVENTIONS Patients were randomized to receive either anaerobically prepared pooled donor FMT (n = 38) or autologous FMT (n = 35) via colonoscopy followed by 2 enemas over 7 days. Open-label therapy was offered to autologous FMT participants at 8 weeks and they were followed up for 12 months. MAIN OUTCOMES AND MEASURES The primary outcome was steroid-free remission of UC, defined as a total Mayo score of Յ2 with an endoscopic Mayo score of 1 or less at week 8. Total Mayo score ranges from 0 to 12 (0 = no disease and 12 = most severe disease). Steroid-free remission of UC was reassessed at 12 months. Secondary clinical outcomes included adverse events. RESULTS Among 73 patients who were randomized (mean age, 39 years; women, 33 [45%]), 69 (95%) completed the trial. The primary outcome was achieved in 12 of the 38 participants (32%) receiving pooled donor FMT compared with 3 of the 35 (9%) receiving autologous FMT (difference, 23% [95% CI, 4%-42%]; odds ratio, 5.0 [95% CI, 1.2-20.1]; P = .03). Five of the 12 participants (42%) who achieved the primary end point at week 8 following donor FMT maintained remission at 12 months. There were 3 serious adverse events in the donor FMT group and 2 in the autologous FMT group. CONCLUSIONS AND RELEVANCE In this preliminary study of adults with mild to moderate UC, 1-week treatment with anaerobically prepared donor FMT compared with autologous FMT resulted in a higher likelihood of remission at 8 weeks. Further research is needed to assess longer-term maintenance of remission and safety.

Gastrointestinal disturbance is frequently reported for individuals with autism. We used quantitative real-time PCR analysis to quantify fecal bacteria that could influence gastrointestinal health in children with and without autism. Lower relative abundances of Bifidobacteria species and the mucolytic bacterium Akkermansia muciniphila were found in children with autism, the latter suggesting mucus barrier changes.Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder where gastrointestinal (GI) disturbance is commonly reported (11). Evidence is emerging that the profiles of the GI microbiota (8,9,16,22) and fermentation products (2, 28) in individuals with ASD are different from those of the general population. Finegold et al. (9) have reported a relationship between regressive autism and altered GI microbiota. Indeed, the modulation of intestinal microbiota in children with ASD through the use of antibiotics (19) and probiotics such as Lactobacillus plantarum WCSF1 (17) has been shown to improve behavior and bowel health outcomes. In this study, various GI bacteria, including Clostridium spp., members of the Bacteroides fragilis group, Akkermansia muciniphila, and Prevotella species, which are emerging as important markers of GI health, were examined in children with ASD, their siblings, and community controls. We also investigated whether correlations exist between GI microbial abundances and the presence or absence of caregiver-reported functional GI disorders (FGIDs) in children with ASD.The inclusion criteria for participants were as previously described (26). Briefly, fecal samples were collected from children with ASD (n ϭ 23), recruited through Autism SA, who were diagnosed by a multidisciplinary team using the childhood autism rating scale (20) and/or the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (3). The ASD participants were diagnosed with autistic disorder (n ϭ 17) and Asperger's syndrome (n ϭ 6), and all but three participants were reported to have a regressive form of autism. Children who met the criteria for ASD but presented with a comorbid diagnosis of a chromosomal abnormality were excluded from the study. We also recruited 22 typically developing siblings (SIB) of the ASD cohort as well as 9 unrelated community controls (CON) without a family history of autism as two different control groups. The CON participants were eligible to participate if they did not have a sibling or first cousin with ASD. Participants' caregivers were required to complete a functional gastrointestinal disorder (FGID) questionnaire (21) and a questionnaire that investigated medication use.Fresh fecal specimens were collected from participants over a 48-h period to exclude day-to-day variability. Each bowel movement was collected in a separate bag and frozen immediately in a portable freezer and stored at Ϫ20°C. Specimens were transported to the laboratory in freezers and stored at Ϫ80°C until they were processed. Specimens were defrosted at room temperature, and all processing was...

BackgroundA recent report indicated that numbers of Sutterella spp. are elevated in gastrointestinal biopsies taken from children with autism spectrum disorder (ASD). We have recently reported changes in the numbers of some bacteria within the stool of ASD children, and now examine whether numbers of Sutterella spp. and some other mucosa-associated bacteria linked with gastrointestinal disease (Ruminococcus gnavus and Ruminococcus torques) are also altered in the stool of these children.FindingsWe show that numbers of Sutterella spp. are elevated in feces of ASD children relative to controls, and that numbers of R. torques are higher in the children with ASD with a reported functional gastrointestinal disorder than those without such a disorder.ConclusionsWe show further evidence of changes in the gut microbiota of children with ASD and confirm that the abundance of Sutterella spp. is altered in stool.

Our results suggest fermentation processes or utilization of fermentation products may be altered in children with ASD compared to children without ASD.

BackgroundProbiotics purportedly reduce symptoms of gastrointestinal and upper respiratory-tract illness by modulating commensal microflora. Preventing and reducing symptoms of respiratory and gastrointestinal illness are the primary reason that dietary supplementation with probiotics are becoming increasingly popular with healthy active individuals. There is a paucity of data regarding the effectiveness of probiotics in this cohort. The aim of this study was to evaluate the effectiveness of a probiotic on faecal microbiology, self-reported illness symptoms and immunity in healthy well trained individuals.MethodsCompetitive cyclists (64 males and 35 females; age 35 ± 9 and 36 ± 9 y, VO2max 56 ± 6 and 52 ± 6 ml.kg-1.min-1, mean ± SD) were randomised to either probiotic (minimum 1 × 109 Lactobacillus fermentum (PCC®) per day) or placebo treatment for 11 weeks in a double-blind, randomised, controlled trial. The outcome measures were faecal L. fermentum counts, self-reported symptoms of illness and serum cytokines.ResultsLactobacillus numbers increased 7.7-fold (90% confidence limits 2.1- to 28-fold) more in males on the probiotic, while there was an unclear 2.2-fold (0.2- to 18-fold) increase in females taking the probiotic. The number and duration of mild gastrointestinal symptoms were ~2-fold greater in the probiotic group. However, there was a substantial 0.7 (0.2 to 1.2) of a scale step reduction in the severity of gastrointestinal illness at the mean training load in males, which became more pronounced as training load increased. The load (duration×severity) of lower respiratory illness symptoms was less by a factor of 0.31 (99%CI; 0.07 to 0.96) in males taking the probiotic compared with placebo but increased by a factor of 2.2 (0.41 to 27) in females. Differences in use of cold and flu medication mirrored these symptoms. The observed effects on URTI had too much uncertainty for a decisive outcome. There were clear reductions in the magnitude of acute exercise-induced changes in some cytokines.ConclusionL. fermentum may be a useful nutritional adjunct for healthy exercising males. However, uncertainty in the effects of supplementation on URTI and on symptoms in females needs to be resolved.Trial registrationThe trial was registered in the Australia and New Zealand Clinical Trials Registry (ACTRN12611000006943).

Butyrate and other SCFA produced by bacterial fermentation of resistant starch (RS) or nonstarch polysaccharides (NSP) promote human colonic health. To examine variation in fecal variables, especially butyrate, among individuals and the response to these fibers, a randomized cross-over study was conducted that compared the effects of foods supplying 25 g of NSP or 25 g of NSP plus 22 g of RS/d over 4 wk in 46 healthy adults (16 males, 30 females; age 31-66 y). Fecal SCFA levels varied widely among participants at entry (butyrate concentrations: 3.5-32.6 mmol/kg; butyrate excretions: 0.3-18.2 mmol/48 h). BMI explained 27% of inter-individual butyrate variation, whereas protein, starch, carbohydrate, fiber, and fat intake explained up to 16, 6, 2, 4, and 2% of butyrate variation, respectively. Overall, acetate, butyrate, and total SCFA concentrations were higher when participants consumed RS compared with entry and NSP diets, but individual responses varied. Individual and total fecal SCFA excretion, weight, and moisture were higher than those for habitual diets when either fiber diet was consumed. SCFA concentrations (except butyrate) and excretions were higher for males than for females. Butyrate levels increased in response to RS in most individuals but often decreased when entry levels were high. Fecal butyrate and ammonia excretions were positively associated ((2) = 0.76; P < 0.001). In conclusion, fecal butyrate levels vary widely among individuals but consuming a diet high in RS usually increases levels and may help maintain colorectal health.

To further understand how diets containing high levels of fibre protect against colorectal cancer, we examined the effects of diets high in nonstarch polysaccharides (NSP) or high in NSP plus resistant starch (RS) on the composition of the faecal microbial community in 46 healthy adults in a randomized crossover intervention study. Changes in bacterial populations were examined using denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene fragments. Bacterial profiles demonstrated changes in response to the consumption of both RS and NSP diets [analysis of similarities (ANOSIM): R=0.341-0.507, P<0.01]. A number of different DGGE bands with increased intensity in response to dietary intervention were attributed to as-yet uncultivated bacteria closely related to Ruminococcus bromii. A real-time PCR assay specific to the R. bromii group was applied to faecal samples from the dietary study and this group was found to comprise a significant proportion of the total community when individuals consumed their normal diets (4.4+/-2.6% of total 16S rRNA gene abundance) and numbers increased significantly (+/-67%, P<0.05) with the RS, but not the NSP, dietary intervention. This study indicates that R. bromii-related bacteria are abundant in humans and may be significant in the fermentation of complex carbohydrates in the large bowel.