The immune system of the infant is functionally immature and naïve. Human milk contains bioactive proteins, lipids, and carbohydrates that protect the newborn and stimulate innate and adaptive immune development. This review will focus on the role human milk oligosaccharides (HMO) play in neonatal gastrointestinal and systemic immune development and function. For the past decade, intense research has been directed at defining the complexity of oligosaccharides in the milk of many species and is beginning to delineate their diverse functions. These studies have shown that human milk contains a higher concentration as well as a greater structural diversity and degree of fucosylation than the milk oligosaccharides in other species, particularly bovine milk from which many infant formulae are produced. The commercial availability of large quantities of certain HMO has furthered our understanding of the functions of specific HMO, which include protecting the infant from pathogenic infections, facilitating the establishment of the gut microbiota, promoting intestinal development, and stimulating immune maturation. Many of these actions are exerted through carbohydrate-carbohydrate interactions with pathogens or host cells. Two HMOs, 2′-fucosyllactose (2′FL) and lacto-N-neotetraose (LNnT), have recently been added to infant formula. Although this is a first step in narrowing the compositional gap between human milk and infant formula, it is unclear whether 1 or 2 HMO will recapitulate the complexity of actions exerted by the complex mixture of HMO ingested by breastfed infants. Thus, as more HMO become commercially available, either isolated from bovine milk or chemically or microbially synthesized, it is anticipated that more oligosaccharides will be added to infant formula either alone or in combination with other prebiotics.

The impact of human milk oligosaccharides (HMO) on mucosal immunity, gut microbiota and response to rotavirus (RV) infection was investigated in the piglet model. Newborn piglets were fed with formula alone (FF) or formula supplemented with 4 g l À 1 HMO (HMO) or a prebiotic mixture of 9:1 short-chain galactooligosaccharides (3.6 g l À 1 ) and long-chain fructooligosaccharides (0.4 g l À 1 ) (PRE) (n ¼ 19-21 per group) for 15 days. Piglets (n ¼ 7-8) in each dietary group were orally infected with porcine rotavirus (RV) OSU strain on d10, and stool consistency was assessed daily. Blood, small intestine and colonic contents were collected at day 15. Serum RV-specific antibody concentrations, intestinal histomorphology, RV non-structural protein-4 (NSP4) and cytokine mRNA expression were assessed. Colonic content pH, dry matter (DM) and short-chain fatty acid concentrations were measured. Ascending colonic microbiota was analyzed by 16S rRNA gene v1-3 region pyrosequencing. HMO-and PRE-fed groups had shorter duration of diarrhea than FF piglets. Infection changed intestinal histomorphology, increased serum RV-specific antibody response and intestinal RV NSP4 expression, and modulated ileal cytokine expression. HMO enhanced T helper type 1 (interferon-gamma) and anti-inflammatory (interleukin-10) cytokines in the ileum, while prebiotics promoted RV-specific immunoglobulin M response to the infection. RV infection and HMO supplementation altered intraluminal environment and gut microbiota. HMO increased pH and lowered DM of colonic contents and enhanced the abundance of unclassified Lachnospiraceae, which contains numerous butyrate-producing bacteria. In conclusion, HMO and prebiotics did not prevent the onset of RV infection but reduced the duration of RV-induced diarrhea in piglets, in part, by modulating colonic microbiota and immune response to RV infection.

Human milk (HM) is rich in oligosaccharides (HMO) that exert prebiotic and anti-infective activities. HM feeding reduces the incidence of rotavirus (RV) infection in infants. Herein, the anti-RV activity of oligosaccharides was tested in an established in vitro system for assessing cellular binding and viral infectivity/replication, and also tested in a newly developed, acute RV infection, in situ piglet model. For the in vitro work, crude HMO isolated from pooled HM, neutral HMO (lacto-N-neotetraose, LNnT; 2 0 -fucosyllactose) and acidic HMO (aHMO, 3 0 -sialyllactose, 3 0 -SL; 6 0 -sialyllactose, 6 0 -SL) were tested against the porcine OSU strain and human RV Wa strain. The RV Wa strain was not inhibited by any oligosaccharides. However, the RV OSU strain infectivity was dose-dependently inhibited by sialic acid (SA)-containing HMO. 3 0 -SL and 6 0 -SL concordantly inhibited 125 I-radiolabelled RV cellular binding and infectivity/replication. For the in situ study, a midline laparotomy was performed on 21-d-old formula-fed piglets and six 10 cm loops of ileum were isolated in situ. Briefly, 2 mg/ml of LNnT, aHMO mixture (40 % 6 0 -SL/10 % 3 0 -SL/50 % SA) or media with or without the RV OSU strain (1 £ 10 7 focus-forming units)were injected into the loops and maintained for 6 h. The loops treated with HMO treatments þ RV had lower RV replication, as assessed by non-structural protein-4 (NSP4) mRNA expression, than RV-treated loops alone. In conclusion, SA-containing HMO inhibited RV infectivity in vitro; however, both neutral HMO and SA with aHMO decreased NSP4 replication during acute RV infection in situ.Key words: Human milk oligosaccharides: Rotavirus: Piglets: Infection Rotaviruses (RV) are double-stranded RNA viruses of the family Reoviridae, which are the most common viral agents causing viral gastroenteritis and diarrhoea in infants and young children worldwide. Each year, approximately 1·4 billion episodes of RV gastroenteritis (RVGE) occur in children under 5 years of age in developing countries, and half a million children die (1,2) .Vaccination is the main public health intervention to prevent RV infection. Systematic reviews of vaccine effectiveness and vaccination-impact studies in industrialised countries (USA, Europe and Australia) have demonstrated an effectiveness of 85 -100 % associated with decreased hospitalisations for RVGE (3) . Vaccination-impact studies have demonstrated that the burden of RVGE has been reduced significantly since the introduction of RV vaccination (3) . However, efficacy trials in developing countries in Africa and Asia showed that vaccine efficacy was lower than that observed in other countries, typically 40 -70 % (4) . Although the efficacy of RV vaccines correlates closely with the national per capita income (5) , it is unclear why vaccination is less efficacious in developing countries (6) . This reduced vaccine efficacy coupled with the high cost and barriers to a widespread distribution of RV vaccines (7) suggest that other means for preventing RV should...

Genetics of taste Lab citizen Scientists † oral microbiome dysbiosis has been associated with various local and systemic human diseases such as dental caries, periodontal disease, obesity, and cardiovascular disease. Bacterial composition may be affected by age, oral health, diet, and geography, although information about the natural variation found in the general public is still lacking. in this study, citizen-scientists used a crowdsourcing model to obtain oral bacterial composition data from guests at the Denver Museum of nature & Science to determine if previously suspected oral microbiome associations with an individual's demographics, lifestyle, and/or genetics are robust and generalizable enough to be detected within a general population. consistent with past research, we found bacterial composition to be more diverse in youth microbiomes when compared to adults. Adult oral microbiomes were predominantly impacted by oral health habits, while youth microbiomes were impacted by biological sex and weight status. the oral pathogen Treponema was detected more commonly in adults without recent dentist visits and in obese youth. Additionally, oral microbiomes from participants of the same family were more similar to each other than to oral microbiomes from non-related individuals. these results suggest that previously reported oral microbiome associations are observable in a human population containing the natural variation commonly found in the general public. furthermore, these results support the use of crowdsourced data as a valid methodology to obtain community-based microbiome data. Oral microbiome dysbiosis has been associated with various local and systemic human diseases including dental caries, periodontal disease, obesity, and cardiovascular disease 1-5. Proper oral health care habits can help reduce abundance of taxa associated with pathogenic states. For example, flossing has been associated with decreased concentrations of the dental pathogen Streptococcus mutans 6 , and brushing of the teeth and tongue significantly decreases microbes associated with dental diseases 7,8. It is estimated that over 600 bacteria species are commonly associated with the oral microbiome, with a subset of these proposed to be part of a consortium called the "core oral microbiome" 9-11. Genera often considered associated with the core microbiome include Streptococcus, Veillonella, Neisseria, and Actinomyces, which are shared by most healthy individuals 12,13. Maintaining the balance of core healthy bacteria in the oral microbiota plays a critical role not only in oral health but in overall health. Oral microbiome composition is suspected to be affected by additional variables including host genetics 14,15 , geography 4,16 , diet 17,18 , age 19-21 , and cohabitation 22-24. For example, comparative studies between European, African, Asian, and American populations discovered microbial variation between populations, and other studies describe ethnicity-specific clustering within the United States 15,25,26. The effect of diet...