Human microbiota: determining dietary factors on the journey from infants to adults

The human microbiota profile changes with age from birth. The early colonisers of the infants’ guts are vital for their current health and also that in later ages of their lives. Determining factors affecting gut microbiota composition across ages are also critical. The thesis aims to understand gut microbiota composition from infants to adults and access to diet as its major modulating factor in healthy children and adults. Faecal microbiota was assessed using 16s rRNA amplicon sequencing in the motherchild pairs (less than one month-48 months in Study I), children (7-12 years in Study II), and adults from two dietary intervention studies (18-40 years in Study III and IV). The first study in this thesis revealed that transmission of the unique gut microbiota, Prevotella, from Indonesian mothers to their infants was successfully established but developed slowly after the weaning period when the infants’ gut microbiota, Bifidobacterium profile, changed to the adult-type, Prevotella. The weaning period (6-12 months old) is a remarkable period of alteration of gut microbiota, the immune responses (cytokines), and bile acids metabolism. After this, the diet is the primary factor influencing the gut microbiota of children. The second study disclosed that geographical location varies the gut microbiotas of Chinese and Malay children from China and two Malaysian cities into two clusters (Bacteroides and Prevotella). The location differences uncovered that the diet is the key influencing factor but not ethnicity. The third study showed that the gut microbiotas of Singaporean young adults could be divided into three clusters (Bacteroides, Prevotella, and Blautia) based on their dietary habits. The Blautia cluster (having randomly rotating Western/Southeast Asian foods) benefited from downregulated immune-regulation without changing its enterotype after the consumption of Lactobacillus-administered milk drink. The Bacteroides cluster resisted changing its enterotype and had a very slight response regarding the alteration of cytokine. The Prevotella cluster decreased its enterotype with upregulated (anti-inflammatory cells) and balanced immunoregulation. The final study found that the abundance of Bacteroides in the gut of Singaporean adults was significantly reduced following a polyphenol-rich meal containing mixed spices. Notably, the abundance of Bifidobacterium was enhanced after a meal with a high-dose of spices. Understanding gut microbiota development in infants, children, and adults and modifying its composition with beneficial microbes (probiotics) and polyphenols may promote the design of new dietary regimens and foods. These may have beneficial effects on health.Ihmisen mikrobisto: koostumukseen vaikuttavia ravitsemustekijöitä lapsista aikuisiin Ihmisen mikrobistoprofiili muokkautuu syntymässä ja vaiheittain sen jälkeen. Lapsen suoliston varhainen kolonisaatio on merkittävä myöhemmän terveyden kannalta. Suoliston mikrobiston koostumukseen vaikuttavat mm. lapsen ikä, syntymätapa, ympäristötekijät ja ravinto. Tämän tutkimuksen tavoitteena oli karakterisoida suoliston mikrobiston koostumus, sen muutokset ja ravintotekijöiden vaikutus eri ikäkausina. Mikrobistomääritykset tehtiiin 16s rRNA amplicon sekvensointia käyttäen. Tutkittavia olivat osatutkimuksessa I äiti-lapsi parit (lapset 1-48 kk), osatutkimuksessa II lapset (7-12 v) ja osatutkimuksissa III ja IV aikuiset (18-40 v). Ensimmäisessä tutkimuksissa todettiin, että Indonesialaisila äideillä vallitseva mikrobisuku on Prevotella, joka siirtyy herkästi lapselle imetyksen aikana. Vieroituksen jälkeen siirtymä aleni nopeasti. Samanaikaisesti imeväisikäisten lasten bifidobakteeri-valtainen mikrobisto muuttui vieroituksessa (6–12 kk) aikuisten kaltaiseksi. Vieroituksen jälkeen ruokavalio oli keskeinen pikkulasten suoliston mikrobiston muokkaaja. Toinen tutkimus osoitti että maantieteellinen sijainti muodosti merkittävän ympäristö- ja ravitsemustekijän: Kiinasta ja kahdesta Malesian kaupungista kotoisin olevien kiinalaisten ja malaiji-lasten mikrobiston havaittiin jakaantuvan Bacteroides- ja Prevotella-klusteriin. Kolmas tutkimus osoitti Singaporen nuorten aikuisten suoliston mikrobiston jakautuvan kolmeen klusteriin (Bacteroides, Prevotella ja Blautia) ja ruokailutottumukset vaikuttivat merkittävästi mikrobiston kehittymiseen. Blautia-klusteri (assosioitui satunnaiseen länsimaisten ruokien käyttöön) vaikutti seerumin sytokiinivasteisiin. Suoliston mikrobiston enterotyyppi ei muuttunut tutkimuksessa, jossa nuoret nauttivat probioottisella laktobasillilla fermentoitua maitojuomaa. Neljäs osatutkimus paljasti Bacteroidesbakteerien määrä singaporelaisten aikuisten suolistossa vähenevän merkittävästi ateriaan liitetyn polyfenolipitoisen mausteseoksen nauttimisen jälkeen. Erityisesti bifidobakteerien määrä lisääntyi suurten mausteannosten jälkeen. Väitökirjatutkimuksen perusteella imeväisten, lasten ja aikuisten suoliston mikrobiston kehityksen tarkempi tunteminen ja koostumuksen muokkaaminen hyödyllisillä mikrobeilla (probiooteilla) ja polyfenoleilla mahdollistaa mikrobistoa muokkaavia ruokien kehittämisen ja ruokailutottumuksien seurannan. Nämä muutokset voivat edistää terveyttä

Indonesian children fecal microbiome from birth until weaning was different from microbiomes of their mothers

Gastrointestinal (GI) microbiota play an important role in human health and wellbeing and the first wave of gut microbes arrives mostly through vertical transmission from mother to child. This study has undertaken to understand the microbiota profile of healthy Southeast Asian mother-infant pairs. Here, we examined the fecal, vaginal and breast milk microbiota of Indonesian mothers and the fecal microbiota of their children from less than 1 month to 48 months old. To determine the immune status of children and the effect of diet at different ages, we examined the level of cytokines, bile acids in the fecal water and weaning food frequency. The fecal microbiota of the children before weaning contained mainlyBacteroidesandBifidobacterium, which presented at low abundance in the samples of mothers. After weaning, the fecal microbiome of children was mainly of thePrevotellatype, with decreasing levels ofBifidobacterium, thus becoming more like the fecal microbiome of the mother. The abundance of infant fecal commensals generally correlated inversely with potential pathogens before weaning. The fecalBifidobacteriumin children correlated inversely with the consumption of complex carbohydrates and fruits after weaning. The specific cytokines related to the proliferation and maturation of immunity were found to increase after weaning. A decreasing level of primary bile acids and an increase of secondary bile acids were observed after weaning. This study highlights the change in the GI microbiota of infants to adult-type microbiota after weaning and identifies diet as a major contributing factor

Gut microbiome of pre-adolescent children of two ethnicities residing in three distant cities

Recent studies have realized the link between gut microbiota and human health and diseases. The question of diet, environment or gene is the determining factor for dominant microbiota and microbiota profile has not been fully resolved, for these comparative studies have been performed on populations of different ethnicities and in short-term intervention studies. Here, the Southern Chinese populations are compared, specifically the children of Guangzhou City (China), Penang City (west coast Malaysia) and Kelantan City (east coast Malaysia). These Chinese people have similar ancestry thus it would allow us to delineate the effect of diet and ethnicity on gut microbiota composition. For comparison, the Penang and Kelantan Malay children were also included. The results revealed that differences in microbiota genera within an ethnicity in different cities was due to differences in food type. Sharing the similar diet but different ethnicity in a city or different cities and living environment showed similar gut microbiota. The major gut microbiota (more than 1% total Operational Taxonomy Units, OTUs) of the children population are largely determined by diet but not ethnicity, environment, and lifestyle. Elucidating the link between diet and microbiota would facilitate the development of strategies to improve human health at a younger age

Gut Microbiome of a Multiethnic Community Possessed No Predominant Microbiota

With increasing globalisation, various diets from around the world are readily available in global cities. This study aimed to verify if multiethnic dietary habits destabilised the gut microbiome in response to frequent changes, leading to readily colonisation of exogenous microbes. This may have health implications. We profiled Singapore young adults of different ethnicities for dietary habits, faecal type, gut microbiome and cytokine levels. Subjects were challenged with Lactobacillus casei, and corresponding changes in microbiome and cytokines were evaluated. Here, we found that the majority of young adults had normal stool types (73% Bristol Scale Types 3 and 4) and faecal microbiome categorised into three clusters, irrespective of race and gender. Cluster 1 was dominated by Bacteroides, Cluster 2 by Prevotella, while Cluster 3 showed a marginal increase in Blautia, Ruminococaceae and Ruminococcus, without a predominant microbiota. These youngsters in the three faecal microbiome clusters preferred Western high sugary beverages, Southeast Asian plant-rich diet and Asian/Western diets in rotation, respectively. Multiethnic dietary habits (Cluster 3) led to a gut microbiome without predominant microbiota yet demonstrated colonisation resistance to Lactobacillus. Although Bacteroides and Prevotella are reported to be health-promoting but also risk factors for some illnesses, Singapore-style dietary rotation habits may alleviate Bacteroides and Prevotella associated ill effects. Different immunological outcome was observed during consumption of the lactobacilli among the three microbiome clusters.</p

Mental awareness improved mild cognitive impairment and modulated gut microbiome

There is ample scientific and clinical evidence of the effects of gut microbiota on the brain but no definitive evidence that the brain can affect changes in gut microbiota under the bi-directional gut-brain axis concept. As there is no pharmacotherapeutic intervention for the early stages of cognitive decline, research has focused on cognitive stimulation in reversing or slowing the impairment. Elderly patients diagnosed with mild cognitive impairment underwent a randomized-control trial of mindful awareness practice. Neuropsychological assessments, inflammatory markers, and gut microbiota profiles were tested. Here, we report that their cognitive impairment was improved and associated with changes in gut bacterial profile. A cognition-score-dependent-abundance was observed in Ruminococcus vs Recognition Trials (RT), Digit Span Backward (DSB), Semantic Fluency Span (SFS) and Memory Domain (MD); Coprococcus vs DSB, Color Trails Test 2 (CTT2) and Block Design (BD); Parabacteroides vs DSB and SFS; Fusobacterium vs DSB and CTT2; Enterobacteriaceae vs BD and SFS; Ruminococcaceae vs DSB; Phascolarctobacterium vs MD. The study showed for the first-time, alteration in the cognitive capacity leading to the corresponding changes in microbiota profiles. This strongly suggests that signals from the different segments of brain could dictate directly or indirectly the abundances of specific gut microbes

A single serving of mixed spices alters gut microflora composition: a dose–response randomised trial

10.1038/s41598-021-90453-7Scientific Reports1111126

Indonesian children fecal microbiome from birth until weaning was different from microbiomes of their mothers

10.1080/19490976.2020.1761240Gut Microbes12011-1

Probiotic-directed modulation of gut microbiota is basal microbiome dependent

10.1080/19490976.2020.1736974Gut Microbes12011-2

The species-level composition of the fecal bifidobacterium and lactobacillus genera in Indonesian children differs from that of their mothers

10.3390/microorganisms9091995Microorganisms99199

Gut microbiome of a multiethnic community possessed no predominant microbiota

10.3390/microorganisms9040702Microorganisms9470