Our life expectancy is increasing, leading to a rise in the ageing population. Ageing is associated with a decline in physiological function and adaptive capacity. Altered GI physiology can affect the amount and types of nutrients digested and absorbed as well as impact the intestinal microbiota. The intestinal microbiota is considered a key player in our health, and a variety of studies have reported that microbiota composition is changing during ageing. Since ageing is associated with a decline in GI function and adaptive capacity, it is crucial to obtain insights into this decline and how this is related to the intestinal microbiota in the elderly. Hence, in this review we focus on age-related changes in GI physiology and function, changes of the intestinal microbiota with ageing and frailty, how these are associated and how intestinal microbiota-targeted interventions may counteract these changes.

Ageing is associated with an increased risk of frailty, intestinal microbiota perturbations, immunosenescence and oxidative stress. Prebiotics such as galacto-oligosaccharides (GOS) may ameliorate these ageing-related alterations. We aimed to compare the faecal microbiota composition, metabolite production, immune and oxidative stress markers in prefrail elderly and younger adults, and investigate the effects of GOS supplementation in both groups. In a randomised controlled cross-over study, 20 prefrail elderly and 24 healthy adults received 21.6 g/day Biotis™ GOS (containing 15.0 g/day GOS) or placebo. Faecal 16S rRNA gene-based microbiota and short-chain fatty acids were analysed at 0, 1 and 4 weeks of intervention.Volatile organic compounds were analysed in breath, and stimulated cytokine production, CRP, malondialdehyde, trolox equivalent antioxidant capacity (TEAC) and uric acid (UA) in blood at 0 and 4 weeks. Principle coordinate analysis showed differences in microbial composition between elderly and adults (P≤0.05), with elderly having lower bifidobacteria (P≤0.033) at baseline. In both groups, GOS affected microbiota composition (P≤0.05), accompanied by increases in bifidobacteria (P<0.001) and decreased microbial diversity (P≤0.023). Faecal and breath metabolites, immune and oxidative stress markers neither differed between groups (P ≥ 0.125) nor were affected by GOS (P ≥ 0.236). TEAC values corrected for UA were higher in elderly versus adults (P<0.001), but not different between interventions (P ≥ 0.455). Elderly showed lower faecal bifidobacterial (relative) abundance than adults, which increased after GOS intake in both groups. Faecal and breath metabolites, parameters of immune function and oxidative stress were not different at baseline, and not impacted by GOS supplementation. CLINICALTRIALS. NCT03077529.

Aging is accompanied with increased frailty and comorbidities, which is potentially associated with microbiome perturbations. Dietary fibers could contribute to healthy aging by beneficially impacting gut microbiota and metabolite profiles. We aimed to compare young adults with elderly and investigate the effect of pectin supplementation on fecal microbiota composition, short chain fatty acids (SCFAs), and exhaled volatile organic compounds (VOCs) while using a randomized, double-blind, placebo-controlled parallel design. Fifty-two young adults and 48 elderly consumed 15 g/day sugar beet pectin or maltodextrin for four weeks. Fecal and exhaled breath samples were collected before and after the intervention period. Fecal samples were used for microbiota profiling by 16S rRNA gene amplicon sequencing, and for analysis of SCFAs by gas chromatography (GC). Breath was used for VOC analysis by GC-tof-MS. Young adults and elderly showed similar fecal SCFA and exhaled VOC profiles. Additionally, fecal microbiota profiles were similar, with five genera significantly different in relative abundance. Pectin supplementation did not significantly alter fecal microbiota, SCFA or exhaled VOC profiles in elderly or young adults. In conclusion, aside from some minor differences in microbial composition, healthy elderly and young adults showed comparable fecal microbiota composition and activity, which were not altered by pectin supplementation.

Scope: Inulin‐type fructans are commonly applied in infant formula to support development of gut microbiota and immunity. These inulin‐type fructans are considered to be fermented by gut microbiota, but it is unknown how fermentation impacts immune modulating capacity and whether the process of fermentation is dependent on the infant's age.Methods and results: The in vitro fermentation of chicory fructo‐oligosaccharides (FOS) and native inulin are investigated using pooled fecal inocula of two‐ and eight‐week‐old infants. Both inocula primarily utilize the trisaccharides in FOS, while they almost completely utilize native inulin with degree of polymerization (DP) 3–8. Fecal microbiota of eight‐week‐old infants degrades longer chains of native inulin up to DP 16. This correlates with a higher abundance of Bifidobacterium and higher production of acetate and lactate after 26 h of fermentation. Fermented FOS and native inulin attenuate pro‐inflammatory cytokines produced by immature dendritic cells (DCs), but profiles and magnitude of attenuation are stronger with native inulin than with FOS.Conclusion: The findings demonstrate that fermentation of FOS and native inulin is dependent on the infant's age and fructan structure. Fermentation enhances attenuating effects of pro‐inflammatory responses in DCs, which depend mainly on microbial metabolites formed during fermentation.

Objective: The intestinal microbiota is acknowledged to be essential in brain development and behaviour. Their composition can be modulated by prebiotics such as short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharide (lcFOS). Several studies reported potential health benefit of prebiotics on behaviour. As the prebiotic mixture of scGOS and lcFOS is included in infant formula, we investigated the effects of dietary supplementation with this specific mixture from the day of birth onwards on behaviour and intestinal microbiota development in mice. Method: Healthy male BALB/cByJ mice received, from day of birth, a dietary supplement with or without 3% scGOS:lcFOS (9:1). Behavioural tests were performed pre-weaning, in adolescence, early adulthood and adulthood. We assessed faecal microbiota compositions over time, caecal short-chain fatty acids as well as brain mRNA expression of Htr1a, Htr1b and Tph2 and monoamine levels. Results: Compared to control fed mice, scGOS:lcFOS fed mice showed reduced anxiety-like and repetitive behaviour over time and improved social behaviour in adulthood. The serotonergic system in the prefrontal cortex (PFC) and somatosensory cortex (SSC) was affected by the scGOS:lcFOS. In the PFC, mRNA expression of brain-derived neurotrophic factor (Bdnf) was enhanced in scGOS:lcFOS fed mice. Although the bacterial diversity of the intestinal microbiota was unaffected by the scGOS:lcFOS diet, microbiota composition differed between the scGOS:lcFOS and the control fed mice over time. Moreover, an increased saccharolytic and decreased proteolytic fermentation activity were observed in caecum content. Discussion: Supplementing the diet with scGOS:lcFOS from the day of birth is associated with reduced anxiety-like and improved social behaviour during the developmental period and later in life, and modulates the composition and activity of the intestinal microbiota in healthy male BALB/c mice. These data provide further evidence of the potential impact of scGOS:lcFOS on behaviour at several developmental stages throughout life and strengthen the insights in the interplay between the developing intestine and brain.

Pectins are dietary fibres that modulate T cell immunity, microbiota composition, and fermentation profiles, but how this is influenced by the degree of methyl-esterification (DM) and degree-of-blockiness (DB) of pectin is unknown. Here, we demonstrate that supplementation of DM19(high-DB), DM49(low-DB) and DM43(high-DB) pectins at a low dose increased the frequencies of intestinal T-helper (Th)1 and Th2 cells after 1 week of pectin supplementation in mice, whereas DM18(low-DB) did not. After 4 weeks of supplementation with those pectins, Th1 and Th2 frequencies returned to control levels, whereas Rorγt⁺ regulatory T-cell frequencies increased. These structure-dependent effects could derive from induced shifts in microbiota composition that differed between DM18(low-DB) pectin and the other pectins. T-cell-modulating effects were not short-chain-fatty acid-dependent, but rather through an increase in Aryl-hydrocarbon-receptor-activating components. Thus, pectins with a specific combination of DM and DB have an impact on intestinal T cell-immunity in mice, when supplemented at a low dose.